Article

Acupuncture analgesia in a new rat model of ankle sprain pain

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

The lack of suitable experimental animal models for persistent pain showing clear acupuncture analgesia, has been the major stumbling block in the investigation of the physiological mechanisms of acupuncture analgesia. The present study developed a new rat model of ankle sprain pain and the effect of electroacupuncture (EA) on this model was examined. A common source of persistent pain in humans is the lateral ankle sprain. To model this condition, the rat's right ankle was bent repeatedly, overextending lateral ligaments, for 4 min under halothane anesthesia. The rat subsequently showed swelling of the ankle and a reduced stepping force of the affected limb for the next several days. The reduced stepping force of the limb was presumably due to a painful ankle since systemic injection of morphine produced temporary improvement of weight bearing. EA was applied to the SI-6 acupuncture point on the contralateral forelimb for 30 min under halothane anesthesia. After the termination of EA, behavioral tests measuring stepping force were periodically conducted during the next 4h. EA produced a 40% recovery in the stepping force of the sprained foot lasting for at least 2h. The magnitude of this improvement was equivalent to that obtained after a systemic injection of 2mg/kg of morphine and this improvement of stepping pressure was interpreted as an analgesic effect. The analgesic effect was specific to the acupuncture point since (1). the analgesic effect on the ankle sprain pain model could not be mimicked by EA applied to a nearby point, LI-4 and (2). EA applied to the SI-6 point was not effective in the knee arthritis pain model. The analgesic effect could not be blocked by systemic injection of opioid antagonists naloxone or naltrexone. These data suggest that EA produces a potent analgesic effect on the ankle sprain pain model in the rat. This analgesic effect is produced by applying EA to a site remote from the painful area in a stimulus point-specific way. The present study provides a powerful experimental animal model that can be used for investigating the unique physiological mechanisms involved in acupuncture analgesia.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Más específicamente según el mediador predominante, se describen cuatro fases: una fase inicial en la que se liberan histamina y serotonina, una segunda fase mediada por cininas, una tercera fase (alrededor de las cinco horas) en la cual la liberación prostaglandinas (PGs) es predominante y una cuarta fase vinculada con infiltración local de neutrófilos y activación de ellos (12)(13)(14)(15)(16)(17). El hallazgo de que el pre-tratamiento con EA inhiba el edema, es sugestivo de que pueda inhibir algunas de estas reacciones de la fase no fagocítica como la degranulación de los mastocitos, la expresión de IL-1 y el incremento de SP (14,18,19). Existen reportes de disminución de SP en la periferia, CDE, núcleo trigeminal, así como la reducción de IL-Iß en tejido sinovial y células del Bazo (15) en modelos de artritis en los que se aplicó la EA (Fig. 1). ...
... Consecuentemente, los autores plantean la hipótesis de que la EA activaría neuronas espinales que transmitirían la señal acupuntural al cerebro y también estimularía al sistema inhibitorio endógeno, el cual pudiera inhibir la hiperalgesia y la expresión de proteína Fos en la parte medial de la Láminas I-II del cordón espinal (20). Ellos observaron además, que la EA aplicada durante 30 minutos, no tiene efecto sobre la expresión de Fos en la parte medial de las láminas superficiales, pero induce su expresión en la mitad lateral de estas láminas y en todas las regiones de las láminas III-IV, VII-IX y X. Otras investigaciones han establecido que ambos sistemas descendentes, el inhibidor y el facilitador, modulan la transmisión de los impulsos nociceptivos a nivel espinal (5)(6)(7)19,21,25). Los autores sugieren que el estímulo prolongado pudiera activar el sistema facilitador descendente atenuando la inhibición del dolor en este modelo de dolor inflamatorio (20) (FIg. ...
... Los AINE como inhibidores de la ciclooxigenasa 2 (COX-2), al disminuir los prostanoides y la sensibilización de nociceptores en la periferia, también por sus efectos a nivel subcortical al causar descenso de los niveles de prostaglandinas E2 (PGE2), además de influir sobre otros sistemas centrales inhibitorios (28-30) y la EA por su mecanismo opiode dependiente, que determina un balance inhibitorio en CDE sobre los aminoácidos excitatorios. También por disminución de SP, determinado por técnicas inmunorreactivas, puede reducir la respuesta electrofisiológica de las neuronas en los circuitos espinales (2,(17)(18)(19) y evidentemente la participación de varios mecanismos biológicos explicaría el efecto sinérgico de esta combinación. ...
Article
Full-text available
Animal models of pain have permitted in the last decades important advances in neurobiologic research, but biological systems are not exact and there are multiple factors that can lead to contradictory results. Those difficulties are exacerbated in models addressed to electroacupuncture treatment procedures, as a parametric variability exists for the liberation of mediators, also for the response of biochemical systems manipulated under physiologic or pathological conditions, among other the influence of the stress induced analgesia (SIA). Our purpose is to critically analyze some recent experiments in this field, from authors that have faced these difficulties and still have provided important elements for the clarification of the mechanisms involved in acupuncture analgesia.
... However, 2 rat ankle-sprain models have been validated as joint arthralgia models and used in analgesia and pain research. 19 Therefore, the purpose of our study was to assess temporal alterations in the muscle activity of 2 periarticular muscles of the rat ankle and 2 proximal muscles of the rat hind limb after an ankle sprain. We evaluated the biceps femoris (BF), medial gastrocnemius (MG), vastus lateralis (VL), and tibialis anterior (TA) muscles, as these muscles have been found to display alterations in humans with ankle injuries 7,8,10,11 and the peripheral nervous system in rats is considered a suitable model for studying the structure and function of neural alterations in humans. ...
... After collecting 2 days of baseline data, we placed the rats under anesthesia as described above and induced a mild lateral ankle sprain to the left hind limb as described by Koo et al. 19 Briefly, the ankle joint was moved repeatedly into inversion and plantar flexion for 4 minutes, causing an overextension of the lateral ankle ligaments. When we could move the joint into 1808 of inversion and plantar flexion, we considered its condition to replicate a mild lateral ankle sprain. ...
... As stated, the original purpose of the ankle-sprain rat model was to elicit pain, especially with gait. 19,36À38 The increased pain due to ankle sprains in these previous studies was confirmed by examining the amount of weight-bearing force on the affected limb 19,36À38 and the quality of vocalizations during gait. 19 In our study, the increased sample entropy beyond the MDC in the VL and TA may have been due to increased ankle pain. ...
Article
Context: The mechanisms that contribute to the development of chronic ankle instability are not understood. Investigators have developed a hypothetical model in which neuromuscular alterations that stem from damaged ankle ligaments are thought to affect periarticular and proximal muscle activity. However, the retrospective nature of these studies does not allow a causal link to be established. Objective: To assess temporal alterations in the activity of 2 periarticular muscles of the rat ankle and 2 proximal muscles of the rat hind limb after an ankle sprain. Design: Controlled laboratory study. Setting: Laboratory. Patients or other participants: Five healthy adult male Long Evans rats (age = 16 weeks, mass = 400.0 ± 13.5 g). Intervention(s): Indwelling fine-wire electromyography (EMG) electrodes were implanted surgically into the tibialis anterior, medial gastrocnemius, vastus lateralis, and biceps femoris muscles of the rats. We recorded baseline EMG measurements while the rats walked on a motor-driven treadmill and then induced a closed lateral ankle sprain by overextending the lateral ankle ligaments. After ankle sprain, the rats were placed on the treadmill every 24 hours for 7 days, and we recorded postsprain EMG data. Main outcome measure(s): Onset time of muscle activity, phase duration, sample entropy, and minimal detectable change (MDC) were assessed and compared with baseline using 2-tailed dependent t tests. Results: Compared with baseline, delayed onset time of muscle activity was exhibited in the biceps femoris (baseline = -16.7 ± 54.0 milliseconds [ms]) on day 0 (5.2 ± 64.1 ms; t4 = -4.655, P = .043) and tibialis anterior muscles (baseline = 307.0 ± 64.2 ms) on day 3 (362.5 ± 55.9 ms; t4 = -5.427, P = .03) and day 6 (357.3 ± 39.6 ms; t4 = -3.802, P = .02). Longer phase durations were observed for the vastus lateralis (baseline = 321.9 ± 92.6 ms) on day 3 (401.3 ± 101.2 ms; t3 = -4.001, P = .03), day 4 (404.1 ± 93.0 ms; t3 = -3.320, P = .048), and day 5 (364.6 ± 105.2 ms; t3 = -3.963, P = .03) and for the tibialis anterior (baseline = 103.9 ± 16.4 ms) on day 4 (154.9 ± 7.8 ms; t3 = -4.331, P = .050) and day 6 (141.9 ± 16.2 ms; t3 = -3.441, P = .03). After sprain, greater sample entropy was found for the vastus lateralis (baseline = 0.7 ± 0.3) on day 6 (0.9 ± 0.4; t4 = -3.481, P = .03) and day 7 (0.9 ± 0.3; t4 = -2.637, P = .050) and for the tibialis anterior (baseline = 0.6 ± 0.4) on day 4 (0.9 ± 0.5; t4 = -3.224, P = .03). The MDC analysis revealed increased sample entropy values for the vastus lateralis and tibialis anterior. Conclusions: Manually inducing an ankle sprain in a rat by overextending the lateral ankle ligaments altered the complexity of muscle-activation patterns, and the alterations exceeded the MDC of the baseline data.
... To evaluate the level of pain in the arthritic knee, we measured the amount of weight bearing by the affected hind limb on rats as our method recently used 12) . The rat was allowed to walk through a long and harrow acrylic path ...
... On the other hand, other studies failed to reverse EA induced analgesia by opiate antagonists, such as naloxone or LR2 Ameliorates Inflammatory Pain in Rats KOREAN JOURNAL OF ACUPUNCTURE naltrexone, in rabbits 19) , in rats 5,12) , or in humans 20) . Furthermore, opiate antagonists sometimes potentiate EA analgesia in rats 5,21) . ...
... These results suggest that when stimulated with acupuncture, neurogenic spots generate therapeutic effects on the associated visceral disorders and that neurogenic spots may represent truly effective acupoints rather than conventional acupoints, which is supported by our previous study showing that GV1, an acupoint between the tail base and the anus, reveals neurogenic inflammation in colitis and has therapeutic effects on colitis when acupuncture is applied 25 . Our data are consistent with previous animal studies showing that needling at sham or inactive acupoints, located 3-5 mm from active (verum) acupoints, is ineffective or less effective than needling at active acupoints 30,31 . It is known that sensory nerve endings are distributed unevenly over the body and acupoints have a higher density of sensory nerve endings than surrounding areas 32 . ...
... However, in systemic reviews of clinical trials, stimulation of sham acupoints can elicit similar effects as stimulation of verum acupoints in human subjects 35 . Conversely, experimental animal studies have consistently reported the specific effects of active acupuncture are not produced by stimulation of sham acupoints in awake or anesthetized rats 30,31 . The positive effects of sham acupoints in humans may be associated with placebo responses 36 or inadequate selection of sham acupoints that are several millimeters apart from active acupoints but still located in the effective zone of active acupoints. ...
Article
Full-text available
Acupuncture, a traditional medical procedure practised for over 2000 years in Asia, stimulates specific but poorly defined sites called acupoints. To date, no unique anatomical acupoint structures have been found. However, noxious sensory signals from visceral organs produce hypersensitive spots on the skin (neurogenic spots), caused by cutaneous neurogenic inflammation, in the dermatome that overlaps with visceral afferent innervations. Here, we show that an acupoint is one form of neurogenic inflammation on the skin. Various studies have demonstrated that acupoints show mechanical hypersensitivity and have high electrical conductance. Stimulation of acupoints produces needling sensations caused by the activation of small diameter afferent nerve fibres and therapeutic effects on the associated visceral organs, which is likely due to the release of endogenous opioids. The present study provides experimental evidence that neurogenic spots exhibit all the characteristics of the acupoints listed above. In addition, the stimulation of neurogenic spots by electrical, mechanical, or chemical means alleviated pathological conditions in rat colitis and hypertension models via the endogenous opioid system. Our results suggest that acupoints associated with internal organs may be identical to neurogenic inflammatory spots on the skin, which are produced by activation of somatic afferents in abnormal conditions of visceral organs.
... Os entrevistados mensuraram a melhora, nos casos de quadros dolorosos, em relação ao início do tratamento: dos 27 com quadros álgicos, 19 relataram melhora de 60% a 100% na dor, três melhoraram entre 30% e 50%, três de 10% a 20%, um não sentiu melhora e um não soube avaliar. Esse resultado positivo converge com os abundantes estudos sobre a eficácia dessa terapêutica 1,27,28 . Esse efeito é bem-vindo nos casos de dor, porém, deixa intacta a questão da dependência do procedimento e dos significados envolvidos no problema, bem como a questão do autocuidado. ...
Article
Full-text available
The virtues attributed to complementary therapies such as holistic and patient-centered approaches and stimulus for self-healing have been increasingly valued and could theoretically attenuate the current prevailing excessive social medicalization. Among such therapies, acupuncture has been highlighted due to its progressive institutionalization and acceptance. The objective of the current study was to analyze the experience of acupuncture patients in the Brazilian Unified National Health System and its relationship to their care, in light of social medicalization in terms of the constitutive aspects, representations, and users' explanatory models. Thirty patients were interviewed, selected from primary and secondary care services in Florianópolis, Santa Catarina State, Brazil. Important therapeutic results were observed in the principal complaints, sleep, disposition, emotional status, and decreased use of medication. Users' explanatory models and self-care were modified very little, or not at all, by acupuncture treatment. However, the study showed expanded and less iatrogenic care, especially in the primary care setting, in which there was little supply of other associated practices from Chinese medicine.
... Mutual Inhibitory Effects of Electroacupuncture KOREAN JOURNAL OF ACUPUNCTURE model and the analgesic effect has been revealed [7][8][9] . In clinical situations electroacupuncture(EA) on ST36 acupoint is practiced for the treatment of osteoarthritic(OA) pain. ...
Article
Full-text available
Objectives : We examined mutual inhibitory effects of combined acupoints in arthritic pain induce by carrageenan(CA). Electroacupuncture(EA) is considered a potentially useful treatment for arthritis. Although the analgesic effect of acupuncture is well documented, little is understood about its biological basis. There are many previous studies of positive effect of combined acupoint, this study was conducted to see the mutual inhibitory effects produced by combined acupoint(ST36 and PC7) on arthritic rats. Methods : For the induction of inflammatory pain rat model, CA was injected into the knee joint cavity. There are four groups; EA was applied to bilateral PC7 acupoints(PC7 group), ST36 acupoints(ST36 group), and both PC7 and ST36 acupoints(ST36+PC7 group) except for the control group. The pain level were assessed to determine the change in weight bearing force. We also examined the COX-2 expression in dorsal horn using immunohistochemistry and western blot analysis. Results : The ST36+PC7 group data showed the significant reduction of weight bearing force and the induction of COX-2 protein expression compared with the ST36 group. Conclusions : Simultaneous EA applied to the ST36 and PC7 acupoints reduced the analgesic effect of the ST36 group on knee inflammatory pain.
... This will lead to a reduction in patient recovery time for both outpatients and inpatients as well as shorter hospital stays for the patients. Acupuncture is an important treatment approach in the Chinese traditional medicine, and acupuncture anesthesia has long been critically acclaimed by medical researchers [5][6][7][8][9][10][11][12][13]. This study was aimed at acquiring an in-depth understanding of the functionality of 100 Hz EA as a pain relief method among patients undergoing ESWL. ...
Article
Full-text available
Background. Extracorporeal shock wave lithotripsy (ESWL) is the preferred option for urolithiasis treatment. However, intensities of pain may be induced and the sedative anesthetic or analgesics were usually needed. The aim of this study was to develop an improved acupuncture-assisted anesthesia approach in pain relief. Methods. We conducted a single-blind, randomized controlled study in China Medical University Hospital. Patients treated by ESWL due to upper urolithiasis were randomly divided into control group, sham-EA group, and 100 Hz EA group. The high frequency electroacupuncture (EA) was applied at the Weizhong acupoint (100 Hz EA group) for 20 minutes prior to the ESWL. In the sham-EA group, the same procedures were performed as those of 100 Hz EA group but no electric current was given to stimulate the acupoints. In the control group, no action was taken before operation. The information including the numbers and dosage of analgesic requirements, pain score, vital signs, and the satisfaction of procedure was collected. Results. A total of 74 subjects were recruited and we found that the interval to the first request analgesic, the number/total dosage of additional analgesic, recovery time from anesthesia, and the satisfaction were all better in both the 100 Hz EA and the sham-EA group. The 100 Hz EA also showed better relief of painful sensations by delaying the onset of pain. Conclusions. The 100 Hz EA and the sham-EA can effectively relieve pain due to ESWL as well as reducing the dosage of opium analgesic used.
... The effect of the duration of the pulse has yet to be clearly evaluated and there remains no agreement on an appropriate EA pulse width for AA. A range of pulse widths have been used, varying from 0.1 to 5 ms (Huang et al., 2000;Cheng Huang et al., 2002;Ishimaru et al., 1995;Koo, Park, Lim, Chung, & Chung, 2002;Romita et al., 1997). One previous study showed that with a pulse duration of 0.2 ms at 10 times threshold, a brief analgesic response was produced but the persistent response was markedly attenuated; whereas ES with a pulse width of 5 ms or 2 ms produced persistent responses (Romita et al., 1997). ...
... LIV-3 point has been studied in a) treatment of liver injury (18), b) neuroprotective effects against neuronal death in the rat Parkinson's disease model [25], c) uterine contractions [26], and d) hypertension [27]. LI-4 point has been studied in a) efficacy of analgesia [28], b) blood pressure and nerve activity [29 30], c) treatment of colitis (16), d) autonomic nerve activity [31] and e) uterine contraction [32]. Shixuan point has been studied for its anti-hypertensive effects in two-kidney one-clip Goldblatt hypertensive rats [33]. ...
Article
Full-text available
Background: Acupuncture and herbal medicine have been of great benefit to Asian people for centuries. However, the discipline has not been subjected systematically and thoroughly to the rigors of scientific testing. Objective: This article reviews experimental evidence in regard to the vascular mechanisms of acupuncture and herbal medicine in hypertension. We focus on our hypothesis that acupuncture and herbal medicine reduce hypertension through activation of microvascular endothelial nitric oxide synthesis (eNOS). We also examine whether or not our results in experimental renovascular hypertension conform to the meridian theory. Results and conclusion: Acupuncture and herbal medicine 1) reduce experimental renovascular hypertension; 2) increase production of nitric oxide (NO), and contribute to vasodilation in the microvasculature and reduction of peripheral vascular resistance. We concluded that acupuncture and herbal medicine target eNOS and activate its signaling mechanisms, and that the benefits of acupuncture proceed along the meridian of the stimulated acupoint.
... Assignments based on 1 H, 13 C, DEPT, HMQC, HMBC and COSY experiments.Fig.1: Iridoids isolated from Gardenia Jasminoides(1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) Methyl resonance appeared at low field region at δ (2.1, s, H-11) due to presence of 3 ohydroxyl group present at C-8 position. All other signals were similar with compound (1) except H-7 due to lack of double bond. ...
Article
Three new iridoids, Gardenal-I (1), Gardenal-II (2) and Gardenal-III (3), together with nine known iridoid glycosides; geniposide (4), 6-β-hydroxy geniposide (5), 6-α-hydroxy geniposide (6), 6-α-methoxy geniposide (7), feretoside (8), genipin-1-β-gentiobioside (9), shanzhiside (10), lamalbidic acid (11) and picrocrocinic acid (12) were isolated from EtOH extract of G. gasminoides. The structures of the new and known compounds were elucidated on the basis of 1D and 2D-NMR spectroscopic techniques and available literature survey. The isolated compounds (1-12) were tested for antimicrobial and antiprotozoal activities.
... Putting aside the cause of the algesia and the pathway of message transduction, mostly it is expressed by means of body twitching and muscle or vascular contraction, when an animal is subjected to certain external stimuli, and it cannot be expressed in words or actions of such unpleasant degree. Most experimental research on animal algesia is the observation of biological responses to pain, such as tail swinging, screaming, and twitching rates of limbs, but these behaviors are unstable and less objective measurements[1][2][3][4][5][6][7][8][9][10][11]. In previous studies, there have been many algesia experiments using acidic reagents to cause pain, and formalin has been found to have the strongest effect for causing feelings of pain in animals. ...
Article
Muscle vibration measurement has long been an unique scientific study, in general, and the direct reaction of animals to feel pain (algesia), either from vascular or muscle contraction, is a complex perceptual experience. Thus this paper proposes a way to measure animal algesia quantitatively, by measuring the changes in muscle vibration due to a pinprick on the surface of the skin of a Spodoptera litura larva. Using the laser optical triangulation measurement principle, along with a CMOS image sensor, linear laser, software analysis, and other tools, we quantify the subtle object point displacement, with a precision of up to 10 μm, for our chosen Spodoptera litura larva animal model, in which it is not easy to identify the tiny changes in muscle contraction dynamics with the naked eye. We inject different concentrations of formalin reagent (empty needle, 12% formalin, and 37% formalin) to obtain a variety of different muscle vibration frequencies as the experimental results. Because of the high concentrations of reagent applied, we see a high frequency shift of muscle vibration, which can be presented as pain indices, so that the algesia can be quantified.
... Mice are also a more cost effective and feasible way to monitor changes that occur long term after an ankle sprain. Previous research has utilized an ankle sprain model in rats (Hahm, 2007;Kim et al., 2008;Koo et al., 2002; and based on our results mice could also be used to successfully induce and follow after an ankle sprain. Additionally, since the mice are genetically identical and live in the same environment, changes in physical activity levels can be attributed to the ankle sprain and no other secondary variables. ...
Article
Full-text available
We do not know the impact an ankle sprain has on physical activity levels across the lifespan. With the negative conse-quences of physical inactivity well established, understanding the effect of an ankle sprain on this outcome is critical. The objective of this study was to measure physical activity across the lifespan after a single ankle sprain in an animal model. Thir-ty male mice (CBA/J) were randomly placed into one of three groups: the transected calcaneofibular ligament (CFL) group, the transected anterior talofibular ligament (ATFL)/CFL group, and a SHAM group. Three days after surgery, all of the mice were individually housed in a cage containing a solid surface running wheel. Physical activity levels were recorded and aver-aged every week across the mouse’s lifespan. The SHAM mice ran significantly more distance each day compared to the re-maining two running groups (post hoc p = 0.011). Daily dura-tion was different between the three running groups (p = 0.048). The SHAM mice ran significantly more minutes each day com-pared to the remaining two running groups (post hoc p=0.046) while the ATFL/CFL mice ran significantly less minutes each day (post hoc p = 0.028) compared to both the SHAM and CFL only group. The SHAM mice ran at a faster daily speed versus the remaining two groups of mice (post hoc p = 0.019) and the ATFL/CFL mice ran significantly slower each day compared to the SHAM and CFL group (post hoc p = 0.005). The results of this study indicate that a single ankle sprain significantly de-creases physical activity across the lifespan in mice. This de-crease in physical activity can potentially lead to the develop-ment of numerous chronic diseases. An ankle sprain thus has the potential to lead to significant long term health risks if not treated appropriately.
... When working with experimental station without using a transparent tube, as in our study, it is necessary to use general anesthesia in order the animal to be less mobile in acupuncture point ST 36. This is according to Koo et all (2002), Tae (2007) and other autors. ...
... When working with experimental station without using a transparent tube, as in our study, it is necessary to use general anesthesia in order the animal to be less mobile in acupuncture point ST 36. This is according to Koo et all (2002), Tae (2007) and other autors. ...
... When working with experimental station without using a transparent tube, as in our study, it is necessary to use general anesthesia in order the animal to be less mobile in acupuncture point ST 36. This is according to Koo et all (2002), Tae (2007) and other autors. ...
Article
Full-text available
There is consistency in the location of biologically active points (BAP) in humans and animals, so it is assumed that the morphological changes after acupuncture in experimental animals are identical to changesin humans. Most often the experiments are made on rats, using various methods of fixing to ensure immobility during the impact in biologically active points. The aim of this study is to develop a method for immobilization of experimental animals, meeting the requirements of our experiments, in order to demonstrate the morphological changes that occur after acupuncture and to define the optimal conditions for its application. The fixing of the experimental rats can be made with available materials or a special clamp. The used spacers for the experimental rats are basically two types - using a transparent tube and not using a transparent tube. On some animals prior anesthesia is made. After repeated application of a fixative developed by us we reached the following conclusions: 1. The fixing with a transparent tube without the use of anesthesia creates optimal conditions for experiments with needle-pricking of a rat. 2. For immobilization of experimental animals without the use of a tube, prior general anesthetic is required in order to avoid straining of the skeletal muscles and trauma on the psyche of the animal. Today’s trend is to create minimum traumatic conditions for animal fixation without the use of pre-anesthesia. The study complies with the ESA European Directive on animal welfare and is consistent with the Commission for the Ethical Treatment of humans and animals. Key words: acupuncture, biologically active points (BAP), rat, ST 36, acupuncture needle
... When working with experimental station without using a transparent tube, as in our study, it is necessary to use general anesthesia in order the animal to be less mobile in acupuncture point ST 36. This is according to Koo et all (2002), Tae (2007) and other autors. ...
... Equivalent anatomical landmarks were used to locate these points in the rat. The transposition of an acupoint from the known human map to the anatomically comparable position in animals is widely used to determine points in animals [18][19][20][21] and has been demonstrated to be effective [19,22,23]. After cleaning the skin with alcohol swabs, one investigator swiftly inserted two #32 gauge, 0.5" acupuncture needles bilaterally into each hind limb of the rat at GB 30 while another gently held the animal. ...
Article
Full-text available
Although acupuncture analgesia has been reported in clinical trials, its mechanisms have been unclear. It was recently reported that spinal astrocytes-produced interleukin-17A (IL-17A) facilitates inflammatory pain. Hypothesizing that electroacupuncture (EA) would suppress inflammation-enhanced IL-17A synthesis to inhibit pain, we induced hyperalgesia, as measured by decreased paw withdrawal latency (PWL) to a noxious thermal stimulus, by subcutaneously injecting complete Freund's adjuvant (CFA, 0.08 ml, 40 μg Mycobacterium tuberculosis) into the hind paws of rats, or intrathecal (i.t.) IL-17A (400 ng in 10 μl) into the lumbar spinal cord. We then gave EA at acupoint GB30 for two 20-min periods, once immediately after CFA or IL-17A administration and again 2 h post-injection. For sham control, EA needles were inserted into GB30 without stimulation. PWL was measured before and 2.5 and 24 h after injection. Spinal IL-17A, IL-17 receptor A (IL-17RA), and phosphorylated NR1, an essential subunit of the N-methyl D-aspartate receptor (NMDAR), were determined 24 h post-CFA or –IL-17A using immunohistochemistry and western blot. Compared to sham control, EA inhibited CFA-caused thermal hyperalgesia 2.5 and 24 h post-CFA and concurrently suppressed inflammation-enhanced IL-17A and IL-17RA synthesis and NR1 phosphorylation in the ipsilateral spinal cord. EA inhibited IL-17A-produced thermal hyperalgesia, IL-17RA synthesis and NR1 phosphorylation. Our data suggest that EA inhibits inflammatory pain by blocking spinal IL-17A synthesis. Since previous study shows that IL-17A is located in astrocytes and IL-17RA and NR1 are in neurons, the data suggest that EA alleviates pain by modulating glia-neuronal interactions that involve IL-17A, IL-17RA, and NR1 phosphorylation.
... Chronic pain differs fundamentally from acute pain in that it can potentially induce long-term plasticity in the central nervous system during the course of the disease, leading to an association of various modulatory factors to induce distinct changes in perception and behavior. Acupuncture has shown significant analgesic effects in various animal models of chronic pain (Koo et al., 2002;Zhang et al., 2014;Li et al., 2019). However, only a few studies have previously investigated the immediate effect of EA on pain at the different phases of chronic pain. ...
Article
Full-text available
The reward of pain relief caused by acupuncture has been found to be clinically significant. However, the molecular mechanisms underlying acupuncture-induced reward of pain relief in chronic pain remain unclear and have not been analyzed in suitable preclinical models. Here, we investigated whether acupuncture could potentially induce the reward of pain relief and orexin neuronal signaling in the lateral hypothalamus (LH) and exhibit a possible role in electroacupuncture (EA)-induced reward in spared nerve injury (SNI) rats. Therefore, by using conditioned place preference (CPP) paradigm, we noticed that EA induced the preference for cues associated with EA-induced pain relief in the early, but not late, phase of chronic pain. These observations were different from the immediate antihyperalgesic effects of EA. c-Fos/orexin double labeling revealed that EA stimulation on 14 days but not on 28 days after SNI modeling activated greater numbers of c-Fos positive orexin neurons in the LH after the CPP test. Moreover, the administration of an orexin-A antagonist in the LH significantly blocked the reward effects of pain relief induced by EA. Furthermore, by using cholera toxin b subunit combined with c-Fos detection, we found that the orexin circuit from the LH to the nucleus accumbens (NAc) shell was significantly activated after EA induced CPP. Microinjection of the orexin antagonist into the NAc shell substantially attenuated the CPP induced by EA. Intravenous injection of low-dose orexin-A together with EA resulted in significantly greater antihyperalgesia effects and CPP scores. Together, these findings clearly demonstrated that LH orexin signaling could potentially play a critical role in the reward effects of pain relief induced by acupuncture. The observations of the present study extended our understanding of orexin signaling in the LH and its role in EA-induced reward, providing new insights into the mechanisms of acupuncture analgesia.
... Our previous studies using a rat model of peripheral nerve injury suggested that both the opioid and the noradrenergic systems contribute equally to the anti-allodynic effects of EA [15,16,27]. In contrast, Chung and his colleagues have consistently reported that the a-adrenergic receptor antagonist, phentolamine, blocked the analgesic effects of EA on ankle sprain pain in rats, whereas the opioid receptor antagonists, naloxone and naltrexone, failed to block the EA effects [31][32][33]. Intriguingly, the same group reported the opposite mechanism in a different pain rat model; the opioid, but not noradrenergic, system mediates the suppressive effects of EA on capsaicin-induced secondary hyperalgesia [34]. In the present study, phentolamine did not prevent the relieving effects of EA on oxaliplatininduced cold allodynia, while naloxone pretreatment completely blocked the anti-allodynic effects of EA. ...
Article
Full-text available
This study investigated whether and how electroacupuncture (EA) attenuates cold hypersensitivity (allodynia) in a rat model of oxaliplatin-induced neuropathic pain. Cold allodynia [evaluated by immersing the tail into cold water (4 °C) and measuring the withdrawal latency] was induced 3 days after an oxaliplatin administration (6 mg/kg, i.p.). EA stimulation (2/100 Hz, 0.3-ms pulse duration, 0.2-0.3 mA) was delivered to ST36 acupoint or non-acupoint for 20 min. Low-frequency (2 Hz) EA at ST36 relieved cold allodynia more effectively than high-frequency EA at ST36 or low-frequency EA at non-acupoint. Naloxone (opioid antagonist, 2 mg/kg, i.p.) completely blocked such EA-induced anti-allodynia, whereas phentolamine (α-adrenergic antagonist, 2 mg/kg, i.p.) did not. Moreover, plasma β-endorphin levels significantly increased right after the end of EA and subsequently decreased. These results indicate that low-frequency EA at ST36 in rats has a marked relieving effect on oxaliplatin-induced cold allodynia that is mediated by the endogenous opioid, but not noradrenergic, system.
... The rats were anesthetized with isoflurane vaporized in air (3% for induction and 2.0% for maintenance). Ankle sprain was produced by manually overextending the lateral ligaments by the same person, without breaking them, to imitate a lateral ankle sprain in a human 19,20 . Anesthesia was discontinued and the rats recovered from anesthesia within 5-10 minutes. ...
Article
Full-text available
Although transcutaneous electrical nerve stimulation (TENS) has been proposed to modulate pain and the mechanisms underlying analgesia remain poorly understood, evidence of anti-inflammatory effect is more limited. The purpose of this study was to examine the opioidergic mechanisms of TENS effects in two different frequencies on pain and inflammatory edema in the ankle sprain model in rats. Threshold to mechanical stimulation was utilized to examine the changes produced by intraperitoneal injection of non-selective opioid antagonist naloxone on the antihyperalgesic effect induced by a 20-min period of 2Hz or 100Hz TENS in the ankle sprain model, produced by manually overextending the lateral ligaments. Ankle sprain induced a long-lasting reduction in paw withdrawn latency (PWL) after 30 minutes for up to 24 hours in sham TENS (SH-TENS) treated rats. The reduced PWL after the induction of ankle sprain was restored partially at 0,1,2,3 and 6, but not 24 hours, after the termination of 2 Hz-TENS (LF-TENS). In 100Hz (HF-TENS) the reduction in PWL was shorter than LF-TENS and both LF and HF effects were fully blocked in naloxone-treated rats. LF- and HF-TENS treated rats did not reach the elevation of edema and presented a progressive edema reduction for over 24 hours when compared to SH-TENS group. Both effects were reduced by naloxone. TENS-induced antihyperalgesic and anti-edematous effects observed in ankle sprain model were mediated by the endogenous opioid system.
... This plant is native to southern Turkey, Cyprus and Iran (9). This plant has many therapeutic applications in China and is used in the treatment of dysmenorrhea, dental pain, a sore throat and rheumatic as well as muscular pain (10)(11). The raw bulb of this medical material has been used as an important drug in traditional Chinese medicine for long years (10). ...
Article
Full-text available
Fritillaria plant belongs to the lily family (Liliaceae) and naturally grows in cold areas, highlands, rocky slopes and cliffs. This study examines the emergence of this plant in the written references of Traditional Persian Medicine (TPM). In this research, we searched native names of Fritillaria imperialis (laleh sarnegoun) in outstanding references of TPM including: Almansori fi Teb, Al-Qanon fi Teb, Al-saidana fi Teb, Al-Abnieh an Haghayegh Al-Advieh, Al-Aghraz Al-Tibbia, Ekhtiyarat Badi’i, Al-Mo’tamed fi Al-AdviehAl-Mofrade, Tazkereh-ye Davoud, Tohfeh Al-Momenin, Makhzan Al-Aladvieh and MohitA’azam. Fritillaria is one among thousands of medical materials added to the pharmacopeia books in TPM from Avicenna’s era (the 4th century AH) up to the13th century AH. In our review, the first report of Fritillaria was found in the book of Tohfeh Al-Mo'menin written by Hakim Mo’men Tonekaboni. He discovered the therapeutic effect of the oil of Fritillaria imperialis against sciatica. TPM was represented as a dynamic medicine, culture characterized by continual expansion of its written references.
... 20 More recently, studies have focused on the antihyperalgesic effect of acupuncture in inflammatory animal models. [25][26][27][28] With persistent inflammation, neuronal plasticity causes hyperalgesia (hyperexcitable to pain). Several studies demonstrated the presence of local and widespread hyperalgesia in patients with unilateral shoulder pain. ...
Article
Full-text available
Background: Strategies for preventing the persistence of pain and disability beyond the acute phase in shoulder pain patients are critically needed. Conventional acupuncture therapy (CAT) or motion style acupuncture therapy (MSAT) alone results in relative improvements in painful conditions in shoulder pain patients; combined interventions may have more global effects. The aim of this study is to evaluate the efficacy and safety of MSAT vs CAT for shoulder pain. Methods: A randomized controlled trial using a factorial design was conducted from January 2014 to December 2015. Patients with a primary complaint of one-sided shoulder pain participated at three study sites. Eligible individuals were randomly assigned to receive MSAT plus minimal CAT (mCAT), CAT plus minimal MSAT (mMSAT), MSAT plus CAT, or mMSAT plus mCAT for 6 weeks in a 1:1:1:1 ratio. The primary outcome was change in shoulder pain intensity (measured using visual analog scale). The secondary outcomes included change in function of the shoulder joint (Constant–Murley score) and the health-related quality of life (Short Form-36 Health Survey). Moreover, perceived credibility of acupuncture was measured using the Treatment Credibility Scale. The outcomes were assessed at baseline and at 6, 10, and 18 weeks after randomization. Analysis of covariance with the baseline score adjustment had been used to determine the primary end point. The between-group differences of MSAT vs mMSAT and CAT vs mCAT were estimated, respectively, after tests of interaction between the two-dimensional interventions. All main analyses followed the intention-to-treat principle. Results: A total of 164 patients completed the study. MSAT was superior to mMSAT in alleviating pain intensity at 10 weeks (P=0.024), and it was maintained for 18 weeks (P=0.013). Statistically significant differences were found when comparing MSAT with mMSAT for improvement in shoulder function (6 weeks, P=0.01; 10 weeks, P=0.006; and 18 weeks, P=0.01), physical health (10 weeks, P=0.023 and 18 weeks, P=0.015), and mental health (18 weeks, P=0.05). No significant differences were found in CAT when compared with mCAT. Conclusion: After 18 weeks of treatment, pain and joint functions are improved more with MSAT than with minimal motion style acupuncture or conventional acupuncture in patients with shoulder pain.
... Traditional Chinese medicine also been used widely in China to reduce pain and swelling and promote recovery of ankle function. It includes herb, acupuncture and massage (Koo et al. 2002;Joshua et al. 2011). Later, further treatment is given according to the diagnosis. ...
... Traditional Chinese medicine also been used widely in China to reduce pain and swelling and promote recovery of ankle function. It includes herb, acupuncture and massage ( Koo et al. 2002;Joshua et al. 2011). Later, further treatment is given according to the diagnosis. ...
Article
ABSTRAK Kecederaan buku lali adalah kejadian yang biasa berlaku dalam mana-mana aktiviti sukan. Tujuan utama kajian adalah untuk menjelaskan anatomi buku lali, mekanisma kecederaan yang berkaitan dengan aktiviti sukan, keabnormalan secara kongenital atau variasi anatomi yang berkaitan dengan kecederaan buku lali serta perbincangan rawatan secara efektif. Suatu tinjauan perpustakaan telah dijalankan untuk mengetahui kecederaan buku lali yang berlaku akibat daripada pelbagai aktiviti sukan. Kami mendokumenkan semua sukan yang melibatkan kecederaan pada sendi buku lali. Anatomi pelbagai struktur bahagian tapak kaki dan keterlibatannya dalam kecederaan dibincangkan dengan teliti. Pengetahuan anatomi tentang kecederaan buku lali boleh memberi manfaat untuk diagnosis akan datang dan bagi tujuan rawatan. ABSTRACT Ankle injuries are commonly seen in various sports. The main aim of the present review was to highlight the normal anatomy of the ankle, mechanism of injuries related to sports, congenital abnormalities or anatomical variations related to ankle injury and discuss its effective management. A review of literature was done to determine the ankle injuries which occur as a result of various sports related activities. We documented all sports which involved injury to the ankle joint. The anatomy of various structures in the sole of foot and their involvement in injuries were discussed at length. The anatomical knowledge of ankle injury may be beneficial for future diagnosis and treatment purpose.
... Thus, intra-articular injection of CFA produced a model of prolonged joint inflammation, as had previously been done with intra-articular injection of sodium urate crystals, which modelled gouty arthritis (Okuda et al. 1984;Coderre and Wall 1987). In addition to joint inflammation, more recent additional procedures have been developed to model surgical joint trauma (Fernihough et al. 2004), ankle sprain (Koo et al. 2002), and whiplash or facet joint loading or distraction (Winkelstein 2011). In addition, attempts have also been made to model specific injury or disease-related types of arthritis, including autoimmune arthritis (Christianson et al. 2010), collagenase-induced arthritis (Seo et al. 2013), mono-iodoacetate-induced arthritis (Ogbonna et al. 2013), obesity-induced arthritis (Griffin et al. 2010), and spontaneous arthritis (Malfait and Schniter 2013). ...
Article
Full-text available
This paper examines the development of and some logistical and methodological issues surrounding the use of animal models of chronic pain. The first section addresses the emergent move towards mechanism-based and disease-related animal models of chronic pain that has accelerated since the late 1980s following publication of Bennett and Xie’s (Pain 33:87–107, 1998) paper on chronic constriction injury of the sciatic nerve and Stein et al.’s (Pharmacol Biochem Behav 31:445–451, 1988) paper on unilateral hind paw inflammation with complete Freund’s adjuvant. The discussion covers vast areas of chronic pain models developed over the past 50 years, starting with the numerous neuropathic, inflammatory and central pain models, as well as the growing number of models developed to study various forms of chronic pain from chronic back pain to visceral pain. It also examines the advantages and disadvantages of tonic pain models, mechanism-based and disease-related models of chronic pain, including issues related to the novel discovery of injury- or disease-related pathophysiological processes, the expansion of testing repertoires, and the successes and failures in the translation of analgesic development from animal preclinical models to human chronic pain conditions. The second section addresses experimental design considerations in the implementation of one of the 3Rs for the use of animal models of chronic pain; that is methods employed to reduce the number of animals used. The discussion covers various issues including the advantages and disadvantages of repeated dose designs and within-group drug testing, including incremental dosing schedules, and crossover designs. It also examines concerns surrounding the stability of symptoms and measures, including varying durations of multiple symptoms and the potential development of nociceptive sensitization, as well as possible use-dependent alterations in drug sensitivity and time-dependent changes in pain processes in specific animal models.
... [24][25][26] Some clinical experience in emergency department and even animal studies indicated that ankle sprain responded rapidly to acupuncture. [27][28][29][30] As the efficacy of acupuncture for treating ankle sprains is optimistic but the evidence is limited, a critical examination of the evidence for the use of acupuncture for ankle sprains is warranted. Thus we decide to do this study to evaluate the evidence for acupuncture's effectiveness and safety for the treatment of ankle sprain. ...
Article
Full-text available
Background: Ankle sprain is one of the most common musculoskeletal injuries in our daily life, which may lead to chronic ankle instability, reducing the quality of patients' life and imposing a heavy burden on social medical security system. There are many kinds of methods treating ankle sprain, which can be divided into the conservative treatments and surgical intervention. Acupuncture is one of the conservative treatments for ankle sprain, especially in China. Therefore, we perform a systematic review and meta-analysis to evaluate the evidence for acupuncture's effectiveness, safety and cost benefits for the treatment. Methods: For the acquisition of required data of eligible randomized controlled trials (RCTs), literature search will be undertaken from the following database: PubMed, Embase, Web of Science, The Cochrane Library, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov, Chinese National Knowledge Infrastructure (CNKI), VIP Database, and Wanfang database. Quality assessment of the included studies will be independently performed according to the Cochrane Risk of Bias Tool by 2 investigators and the level of evidence for results will be assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method. Statistical analysis will be conducted with Revman 5.3. Results: From the study we will assess the effectiveness, safety and cost benefit of acupuncture on pain relief and functional improvement in patients with ankle sprain. Conclusion: The conclusion of this study will provide evidence to ensure the effectiveness, safety and cost benefits of acupuncture on ankle sprain, which can further guide the selection of appropriate interventions. Prospero registration number: CRD42018116829.
Article
Objectives : Electroacupuncture(EA) has been used effectively in producing analgesia on ankle sprain pain of humans and animals. Currently to examine the underlying mechanisms of the EA-induced analgesia, the effects of EA on weight-bearing forces(WBR) were examined at ankle sprain classified as grade 3 in rats. Methods : The severe ankle sprain classified as grade 3 was induced surgically by ankle ligament injury in the Sprague-Dawley rats. WBR of the affected foot were examined to evaluate effects and mechanism of EA(2 Hz, 1 ms pulse width, 2 mA intensity, for 15 min) which was applied to either SI6, GB34, or GB39 acupoints. The rats were pretreated with naltrexone(10 mg/kg, i.p.) as an opioid receptor antagonist or phentolamine(5 mg/kg, i.p) as an -adrenoceptor antagonist at 30 min before EA. Results : The daily repeat EA at either SI6, GB34, or GB39 showed significant analgesic effects on the severe ankle sprain. Particularly, daily EA at GB34 showed more potent analgesic effect than the others. In addition, the naltrexone pretreatment completely blocked the analgesic effect of EA at GB34, indicating the involvement of the endogenous opioid system in mediating the effect of EA at GB34. However, the phentolamine pretreament blocked analgesic effects of EA at either SI6 or GB39, indicating the involvement of -adrenoceptors in mediating the effect of EA at either SI6 or GB39. Conclusions : These data suggest that EA-induced analgesia on ankle sprain pain is mediated through either endogenous opioids or -adrenoceptors dependant on acupoint specific pattern.
Article
Introduction: Ankle sprains are the most common orthopedic pathology experienced during sport and physical activity and often result in chronic ankle instability (CAI). Understanding how to prevent CAI is difficult because of the costs and logistics associated with clinical trials aimed at preventing the heterogeneous symptoms associated with CAI. Thus, a need exists to develop an animal model that presents similar long-term consequences as CAI to assess preclinical data. Thus, the purpose was to determine whether surgically transecting the lateral ligaments of a mouse hind limb results in the development of CAI-like symptoms 12 months after injury. Methods: Thirty male mice (CBA/J) were randomly placed into a SHAM (control), CFL (calcaneofibular ligament; mild ankle sprain), or ATFL/CFL (anterior talofibular ligament/CFL; severe) ankle sprain group and housed individually. Three days after surgically transecting the respective lateral ligaments, mice were given a solid surface running wheel and daily running wheel measurements were recorded. Outcome measures of balance and gait were obtained before and at 4, 48, 54, and 60 wk after injury. Results: The ATFL/CFL group had significantly more hind foot slips than the CFL and SHAM groups (P < 0.05). The CFL also had more hind foot slips relative to the SHAM group (P < 0.05). The ATFL/CFL group was significantly less physically active relative to the SHAM and CFL groups (P < 0.05). A cut score of 4.75 foot slips had a sensitivity of 0.68 and specificity of 1.00 and indicates that 70% (14/20) of mice with an ankle sprain had developed CAI. Conclusions: The results of this study indicate that an acute ankle sprain in mice can result in the development of CAI-like symptoms 12 months after injury.
Article
In the last decade, preclinical investigations of electroacupuncture mechanisms on persistent tissue injury (inflammatory), nerve injury (neuropathic), cancer, and visceral pain have increased. These studies show that electroacupuncture activates the nervous system differently in health than in pain conditions, alleviates both sensory and affective inflammatory pain, and inhibits inflammatory and neuropathic pain more effectively at 2 to 10 Hz than at 100 Hz. Electroacupuncture blocks pain by activating a variety of bioactive chemicals through peripheral, spinal, and supraspinal mechanisms. These include opioids, which desensitize peripheral nociceptors and reduce proinflammatory cytokines peripherally and in the spinal cord, and serotonin and norepinephrine, which decrease spinal N-methyl-D-aspartate receptor subunit GluN1 phosphorylation. Additional studies suggest that electroacupuncture, when combined with low dosages of conventional analgesics, provides effective pain management which can forestall the side effects of often-debilitating pharmaceuticals.
Article
It is important that veterinarians treating exotic companion mammals stay abreast of the latest developments relating to medications and drug delivery approaches for safety, efficacy and welfare issues. Sustained release formulations of commonly used drugs as well as newer routes for administration of therapeutic agents allow the veterinarian treating exotic companion mammals to reduce the stress associated with drug administration. Interactions can occur between vehicle and drugs when formulations are compounded, therefore research studies are warranted regarding potential problems associated with these formulations. Copyright © 2015 Elsevier Inc. All rights reserved.
Article
Context: Ankle sprains are the most common orthopaedic injury that occurs during sport and physical activity. Many individuals who sprain their ankles develop chronic ankle instability (CAI), a condition characterized by recurrent injury, decreased physical activity, and decreased quality of life. These residual impairments are believed to persist for the remainder of the patient's life, in part due to the link between CAI and posttraumatic ankle osteoarthritis. However, this belief remains speculative due to the lack of long-term prospective investigations. Objective: To use a mouse model of mild (MILD) and severe (SEVERE) ankle sprains to quantify balance and locomotor adaptations across the lifespan. Design: Cohort study. Setting: Sports medicine research laboratory. Patients or other participants: Fifty male mice (CBA/J) were randomly placed into a control (SHAM), MILD, or SEVERE group and housed individually. Intervention(s): The MILD group underwent surgical transection of a single right hind-limb lateral ligament, and the SEVERE group had 2 of the lateral ligaments transected. The SHAM group underwent a sham surgery during which no lateral ligaments were transected. Main outcome measure(s): After surgically inducing the ankle sprain, we measured balance and gait using a balance beam and footprint test before and every 6 weeks for 78 weeks. Results: Age-related declines in balance but not stride length were exacerbated by an ankle sprain ( P < .001). Balance and stride lengths changed with age ( P < .001). Foot slips were worse in the SEVERE (4.32 ± 0.98) and MILD (3.53 ± 0.98) groups than in the SHAM group (2.16 ± 0.99; P < .001). Right-limb stride length was shorter in the SEVERE group (6.45 cm ± 0.41 cm) than in the SHAM group (6.87 cm ± 0.40 cm; P = .04). Conclusions: Transecting the lateral ligaments of a mouse hind foot resulted in lifelong sensorimotor dysfunction. Declines starting at 42 weeks postinjury may have represented the onset of posttraumatic osteoarthritis.
Article
As part of our ongoing investigation into the neurological mechanisms of acupuncture, we have tried to correlate the distribution of afferent nerve endings with acupuncture points (AP) in the rat hind limbs. In vivo extracellular microfilament recordings of Aα/Aβ/Aδ fibers were taken from peripheral nerves to search for units with nerve endings or receptive fields (RF) in the skin or the muscles. The location of the RFs for each identified unit was marked on scaled diagrams of the hind limb. Noxious antidromic stimulation-induced Evans blue extravasation was used to map the RFs of C-fibers in the skin or muscles. Results indicate that, for both A- and C-fibers, the distribution of RFs was closely associated with the APs. In the skin, the RFs concentrate either at the sites of APs or along the orbit of meridian channels. Similarly, the majority of sarcous sensory receptors are located at the APs in the muscle. Results from our studies strongly suggest that APs in humans may be excitable muscle/skin–nerve complexes with high density of nerve endings.
Article
Postoperative pain is a major problem. Electroacupuncture (EA) has been accepted as a useful and low-risk complementary therapy for post-operative pain. Animal studies indicate that surgical incision activates p38 MAPK in the spinal microglia, which critically contributes to post-incisional nociceptive development. How EA affects incision-induced p38 activation is important but yet to be fully elucidated. Male adult rats received plantar incision (PI) at the right hind paw followed by 30-min EA of 4-Hz, one of two intensities (3 and 10 mA), and at right ST36 (Zusanli) acupoint immediately after PI and for 3 successive days. EA analgesia was evaluated by von Frey fibers and Hargreaves' tests. Spinal p38 activation was examined by immunostaining. In separate groups, SB203580, a p38 inhibitor, was intrathecally injected alone or with EA to test the combining effect on nociception and spinal phospho-p38. EA of 10-mA significantly ameliorated mechanical allodynia, but 3-mA did not. None of them altered thermal hyperalgesia. Repeated EA could not inhibit phospho-p38 in the PI rats, contrarily, EA per se significantly induced phospho-p38 in the normal rats. Intrathecal SB203580 injection dose-dependently prevented PI-induced allodynia. Combination of low-dose SB203580 and 3-mA EA, which were ineffective individually, profoundly reduce post-PI allodynia. We demonstrated that 10-mA EA exerts a significant inhibition against post-PI mechanical hypersensitivity via a p38-independent pathway. Importantly, co-treatment with low-dose p38 inhibitor and 3-mA EA can counteract spinal phospho-p38 to exert strong analgesic effect. Our finding suggests a novel strategy to improve EA analgesic quality. Copyright © 2015. Published by Elsevier Inc.
Article
The regulation of skin blood flow (SBF) is primarily mediated by the sympathetic nervous system, but the effects of electrical stimulation (ES) of one limb on SBF in the other limbs remain unknown. The present study investigated the effects of unilateral forelimb ES on SBF in the bilateral hindlimbs in anesthetized rats. Bilateral hindlimb ischemia was induced by tourniquet application for 60 min. After reperfusion for 24 h, ES (3 or 125 Hz) was applied to the upper one-fourth of the triceps brachii muscle of the left or right forelimb for 30 min. Rats that did not receive ES were used as the controls. Bilateral hindlimb SBF was measured by a laser Doppler line scanner for 20 min before ES, 30 min during ES, and 9 min after ES. The results showed significant differences in SBF in the right but not left hindlimb between the control group and experimental group that received 125-Hz ES of the right forelimb. Right hindlimb SBF significantly increased within 3 min following the application of 125-Hz ES to the right forelimb. No significant changes in SBF were observed in the left or right hindlimb when 125-Hz ES was applied to the left forelimb. Moreover, 3-Hz ES of the left or right forelimb did not significantly change SBF in either hindlimb compared with the control group. These results indicate that unilateral forelimb ES causes a differential SBF response in the hindlimb via a specific somatosympathetic reflex, and ES-induced SBF improvements in the ischemic hindlimb are frequency-dependent.
Article
Zusammenfassung Einleitung Physiologische Wirkungen der Akupunktur in der Behandlung von Schmerzen sind Gegenstand von über drei Jahrzehnten Forschung. Zielsetzung Aktuelle Übersicht über die Wirkmechanismen der Akupunktur-induzierten Analgesie Methodik Es wurde eine ausführliche Recherche auf der Basis relevanter Übersichtsarbeiten der letzten Jahre, deren Sekundärliteratur („Schneeballrecherche”) und MEDLINE-Recherchen zu den einzelnen Unterpunkten mithilfe gängiger Suchwörter durchgeführt. Die Studienergebnisse wurden entsprechend der folgenden Teilbereiche zusammengefasst: 1 Bedeutung der Endorphine und Aktivierung der absteigenden Schmerzhemmung 2 Wirkung auf das autonome Nervensystem 3 Veränderte zerebrale Schmerzverarbeitung 4 Segmentale Inhibition 5 Lokale Mechanismen Ergebnisse Die Endorphinfreisetzung als anti-nozizeptiver Mechanismus der Akupunktur ist gut belegt. Es bestehen Hinweise auf einen Einfluss der Stimulationsfrequenz im Rahmen der Elektrostimulationsakupunktur (ESA). Belege für die Beteiligung verschiedener Neuromodulatoren – v. a. Serotonin und Noradrenalin – bei der Aktivierung der absteigenden Schmerzhemmung liegen vielfach vor. Wirkungen der Akupunktur auf das autonome Nervensystem scheinen möglich, aber sind noch weitgehend ungeklärt. Die Beeinflussung der zerebralen Schmerzverarbeitung durch Akupunktur ist dagegen gut untersucht, ebenso wie die Aktivierung der segmentalen Hemmung. Gut beschrieben ist die periphere Ausschüttung verschiedenster Neurotransmitter als potenzieller Wirkmechanismus der Akupunkturanalgesie. Schlussfolgerungen Die Akupunktur-induzierte Analgesie beruht auf einem komplexen Zusammenspiel peripherer, spinaler und zerebraler Effekte. Dies ist durch eine große Anzahl an Grundlagenstudien belegt. Offen bleibt, zu welchen Anteilen die einzelnen Mechanismen zur schmerzlindernden Wirkung der Akupunktur beitragen, und auf welche Weise sie zusammenwirken. Erforderlich sind Studien zur Punktspezifität, zum Einfluss verschiedener Stimulationsarten und -intensitäten, sowie insbesondere human-experimentelle Grundlagenstudien, um die Übertragbarkeit der Ergebnisse aus tierexperimentellen Studien zu überprüfen.
Chapter
Anesthesia, sedation and analgesia in small mammals is a rapidly advancing field, which plays a key role in ensuring animal welfare in these species. Anesthesia in small mammals is generally more challenging compared to dogs and cats, due to the small size of the animals, limited intravascular and airway access options and the tendency of many small mammals to hide clinical signs related to underlying diseases. Sedation is increasingly used in small mammals to decrease the stress response secondary to manual restraint and to facilitate a variety of clinical procedures, such as diagnostic imaging. Sedation can frequently be used instead of general anesthesia. Assessing pain can be challenging in small mammal prey species, such as rabbits and rodents. In addition, for many potentially analgesic drugs the efficacy and safety has not been demonstrated in even more common small mammal species.
Article
Background Acupuncture and related techniques are used worldwide to alleviate pain; however, their mechanisms of action are still not fully understood. In the present study, we investigated the effect of transcutaneous electrical acupuncture point stimulation (TEAS) at different frequencies in a chronic constriction injury (CCI) model of neuropathic pain in rats. Methods CCI was induced by ligating the common sciatic nerve, which produced neuropathic pain. 18 male Sprague–Dawley rats with CCI were randomly divided into three groups (n=6 each) that remained untreated (CCI group) or received TEAS at high frequency (CCI+TEAS-H group) or TEAS at low frequency (CCI+TEAS-L group). Rats in the CCI+TEAS-H group received high frequency stimulation (6–9 mA, 100 Hz) at GB34/GV26/ST36; those in the CCI+TEAS-L group received low frequency stimulation (6–9 mA, 2 Hz) at the same points. Rats in the control group had the same electrodes applied but received no stimulation. All three groups were subjected to behavioural studies after treatment. Expression of μ opioid receptors (MORs) in the L3–L5 dorsal root ganglion (DRG) was determined by immunofluorescence staining and Western blotting after treatment. Results Compared with the untreated CCI group, both mechanical allodynia and thermal hypergesia were significantly attenuated, and MOR expression in the DRG was significantly increased by low frequency TEAS treatment at GB34/GV26/ST36 (p<0.05). In contrast, no significant differences were observed between the CCI and CCI+TEAS-H groups. Conclusions The use of low frequency TEAS significantly mitigated neuropathic pain in this rat model, and its analgesic effect is likely mediated by upregulation of MOR expression in the DRG.
Article
Although acupuncture analgesia has been reported in clinical trials, its mechanisms have been unclear. It was recently reported that spinal astrocytes-produced interleukin-17A (IL-17A) facilitates inflammatory pain. Hypothesizing that electroacupuncture (EA) would suppress inflammation-enhanced IL-17A synthesis to inhibit pain, we induced hyperalgesia, as measured by decreased paw withdrawal latency (PWL) to a noxious thermal stimulus, by subcutaneously injecting complete Freund's adjuvant (CFA, 0.08 ml, 40 μg Mycobacterium tuberculosis) into the hind paws of rats, or intrathecal (i.t.) IL-17A (400 ng in 10 μl) into the lumbar spinal cord. We then gave EA at acupoint GB30 for two 20-min periods, once immediately after CFA or IL-17A administration and again 2 h post-injection. For sham control, EA needles were inserted into GB30 without stimulation. PWL was measured before and 2.5 and 24 h after injection. Spinal IL-17A, IL-17 receptor A (IL-17RA), and phosphorylated NR1, an essential subunit of the N-methyl D-aspartate receptor (NMDAR), were determined 24 h post-CFA or -IL-17A using immunohistochemistry and western blot. Compared to sham control, EA inhibited CFA-caused thermal hyperalgesia 2.5 and 24 h post-CFA and concurrently suppressed inflammation-enhanced IL-17A and IL-17RA synthesis and NR1 phosphorylation in the ipsilateral spinal cord. EA inhibited IL-17A-produced thermal hyperalgesia, IL-17RA synthesis and NR1 phosphorylation. Our data suggest that EA inhibits inflammatory pain by blocking spinal IL-17A synthesis. Since previous study shows that IL-17A is located in astrocytes and IL-17RA and NR1 are in neurons, the data suggest that EA alleviates pain by modulating glia-neuronal interactions that involve IL-17A, IL-17RA, and NR1 phosphorylation.
Article
Full-text available
Transient receptor potential vanilloid 1 (TRPV1) and associated signaling pathways have been reported to be increased in inflammatory pain signaling. There are accumulating evidences surrounding the therapeutic effect of electroacupuncture (EA). EA can reliably attenuate the increase of TRPV1 in mouse inflammatory pain models with unclear signaling mechanisms. Moreover, the difference in the clinical therapeutic effects between using the contralateral and ipsilateral acupoints has been rarely studied. We found that inflammatory pain, which was induced by injecting the complete Freund’s adjuvant (CFA), (2.14 ± 0.1, p < 0.05, n = 8) can be alleviated after EA treatment at either ipsilateral (3.91 ± 0.21, p < 0.05, n = 8) or contralateral acupoints (3.79 ± 0.25, p < 0.05, n = 8). EA may also reduce nociceptive Nav sodium currents in dorsal root ganglion (DRG) neurons. The expression of TRPV1 and associated signaling pathways notably increased after the CFA injection; this expression can be further attenuated significantly in EA treatment. TRPV1 and associated signaling pathways can be prevented in TRPV1 knockout mice, suggesting that TRPV1 knockout mice are resistant to inflammatory pain. Through this study, we have increased the understanding of the mechanism that both ipsilateral and contralateral EA might alter TRPV1 and associated signaling pathways to reduce inflammatory pain.
Article
Full-text available
This paper summarizes the scientific session and round-table discussion on acupuncture research held during the North American Research Conference on Complementary and Integrative Medicine, sponsored by the Consortium of Academic Health Centers for Integrative Medicine (CAHCIM), at Edmonton, Alberta, Canada, May 24-27, 2006. The session. panelists, co-sponsored by the Society for Acupuncture Research, focused on two main challenges in the design of acupuncture clinical trials: selection of appropriate controls and outcome measures. What follows are highlights of each presentation, as provided by the panelist, as well as an edited transcript of the discussion.
Chapter
Pathological conditions producing pain in humans lead to the perception of damaged tissue (nociception) from multiple sites within the body, are evoked by multiple different types of stimuli and produce behavioral, reflex and neurophysiological responses. Models of pain in nonhuman animals have allowed for an improved understanding of the mechanisms of pain and serve as predictors of the potential clinical efficacy of analgesic manipulations. Nonhumans are not able to report pain in the sophisticated way of humans and so experimental paradigms need to be assessed regarding their validity as models of pain. Ideal models use an easily controlled, reproducible stimulus which is pain-producing in humans to produce aversive behaviors in the species being tested. Ideally, responses to this stimulus are quantifiable, reliable, reproducible and are altered by modifiers known to affect a particular clinical pain such as known analgesics or conditions producing hypersensitivity (i.e., inflammation). Using a site-stimulus-response-modifier descriptive nomenclature, the present chapter will describe currently employed models of pain.
Article
Objectives : The objectives of this study is to compare the effects of electroacupuncture(EA), warm needling(WN) and Radio Frequency warm needling(RFWN) stimulations on the acupoints at the artificially damaged ankles of Sprague-Dawley rats, which could be classified as the Grade 3. Methods : The foot weight bearing force ratio(FWBFR) of ankle sprain was measured first at 24 hours after without any other stimulations. Pain Recovery Index(PRI) represents the analgesic level, and modified Pain Recovery Index(mPRI) shows the accumulated recovery level. PRI was measured at 2 hours after each stimulus on GB34, GB39 and GB42, and mPRI was during 7 days. Results : EA stimulation of GB34 and GB39 acupoint in grade 3 ankle sprain showed a marked analgesic and recovery effect. RFWN of GB42 exhibited significant analgesic and pain recovery effect. RFWN of GB34 resulted in pain recovery effect but not analgesic effects, and RFWN of GB39 resulted in analgesic effect 2 hours after but not pain recovery. However, WN did not affect the pain recovery among three acupoints at all. Conclusions : In the Grade 3 ankle sprain model, the difference of analgesic effects were explained by the acupoints and the stimulation methods according to the accumulated recovery effects during 7 days. It is insufficient to determine that a certain acupoint has a specific analgesic effect depending on the stimulation method by the results of this study. Therefore, the effects of each stimulation on the acupoints in any other meridians at the sprained ankle should be compared and analyzed.
Article
Full-text available
A prior national survey documented the high prevalence and costs of alternative medicine use in the United States in 1990. To document trends in alternative medicine use in the United States between 1990 and 1997. Nationally representative random household telephone surveys using comparable key questions were conducted in 1991 and 1997 measuring utilization in 1990 and 1997, respectively. A total of 1539 adults in 1991 and 2055 in 1997. Prevalence, estimated costs, and disclosure of alternative therapies to physicians. Use of at least 1 of 16 alternative therapies during the previous year increased from 33.8% in 1990 to 42.1% in 1997 (P < or = .001). The therapies increasing the most included herbal medicine, massage, megavitamins, self-help groups, folk remedies, energy healing, and homeopathy. The probability of users visiting an alternative medicine practitioner increased from 36.3% to 46.3% (P = .002). In both surveys alternative therapies were used most frequently for chronic conditions, including back problems, anxiety, depression, and headaches. There was no significant change in disclosure rates between the 2 survey years; 39.8% of alternative therapies were disclosed to physicians in 1990 vs 38.5% in 1997. The percentage of users paying entirely out-of-pocket for services provided by alternative medicine practitioners did not change significantly between 1990 (64.0%) and 1997 (58.3%) (P=.36). Extrapolations to the US population suggest a 47.3% increase in total visits to alternative medicine practitioners, from 427 million in 1990 to 629 million in 1997, thereby exceeding total visits to all US primary care physicians. An estimated 15 million adults in 1997 took prescription medications concurrently with herbal remedies and/or high-dose vitamins (18.4% of all prescription users). Estimated expenditures for alternative medicine professional services increased 45.2% between 1990 and 1997 and were conservatively estimated at $21.2 billion in 1997, with at least $12.2 billion paid out-of-pocket. This exceeds the 1997 out-of-pocket expenditures for all US hospitalizations. Total 1997 out-of-pocket expenditures relating to alternative therapies were conservatively estimated at $27.0 billion, which is comparable with the projected 1997 out-of-pocket expenditures for all US physician services. Alternative medicine use and expenditures increased substantially between 1990 and 1997, attributable primarily to an increase in the proportion of the population seeking alternative therapies, rather than increased visits per patient.
Article
Full-text available
In the present study 123 patients with chronic pain, consecutively referred for symptomatic pain treatment, were given peripheral conditioning stimulation as an analgesic measure and were followed for 2 years or till they terminated the treatment. The stimulation was either conventional transcutaneous nerve stimulation (TNS) [35] of mainly cutaneous afferents with high frequency (10-100 Hz) or acupuncture-like TNS [11] where muscle nerves are activated at a low repetition rate (1-4 Hz) with small trains of stimuli. The follow-up showed that 55, 41 and 31% of the patients continued the treatment after 3, 12 and 24 months, respectively. About 30% of the patients had to use acupuncture-like TNS to get useful analgesia, defined as a desire of the patient to continue stimulation treatment. Three-quarters of the successfully relieved patients reported more than 50% pain relief as measured from visual analogue scales and half of these reported an increased social activity and a decrease of analgesic drug intake by more than 50%. Psychogenic and visceral pains were less suitable for TNS treatment. It is concluded that peripheral conditioning stimulation is a valuable therapy in cases of chronic pain and that both conventional and acupuncture-like TNS should be tried before considering implantable devices or destructive surgery.
Article
Full-text available
Little is known about the characteristics of American physicians who currently practice acupuncture. We asked: (1) Do the demographics of physicians practicing acupuncture differ from the general physician population? (2) Do these physicians use or endorse other alternative therapies? (3) For which conditions is acupuncture most commonly used? (4) For which conditions is acupuncture perceived to be most efficacious? Mailed survey of physicians who incorporate acupuncture into their practice. Membership of the American Academy of Medical Acupuncture (AAMA). Demographic information regarding physicians and practice characteristics; specific illnesses treated, and perceived efficacy; use of other complementary modalities; personal reasons for practicing acupuncture. Compared with national data, respondents were more likely to be nonspecialists, in private practice, and age 35 to 54. There was an equal proportion of men and women. Most had been doing acupuncture for < 5 years; most use it on < 25% of their patients. Endorsement or use of other complementary methods (spinal manipulation, herbal medicine, supplements, homeopathy) was common. Acupuncture was more commonly used for pain conditions than general medical problems or addiction management. Reasons for use included: efficacy of the technique, an alternative in cases of inadequacy of standard medical approach, and a multidimensional approach to health care. Physicians surveyed in this study who incorporate acupuncture into their practice do so mainly to treat pain problems. They are more likely to be in the 35 to 54 age group, nonspecialists, and in private practice when compared with national averages. These physicians are also more likely to use or endorse other complementary modalities.
Article
Full-text available
This work was designed to elucidate the possible involvement of endogenous endomorphin-I (EM1) in analgesia induced by electroacupuncture of low or high frequencies. Taking radiant heat tail flick latency (TFL) as an indication of nociception, rats were subjected to intrathecal (i.t.) injection of 10 microl antiserum against EM1 (EM1-AS) or normal rabbit serum (NRS, as control) and then followed by 2 or 100 Hz electroacupuncture stimulation for 30 min. The analgesia induced by 2 Hz electroacupuncture was attenuated by i.t. injection of EM1-AS at 1:10 and 1:100 but not at 1:1000 dilution. No such suppressive effect was observed for 100 Hz EA analgesia when EM1-AS was injected i.t. at any dilutions. These results indicate that EM1 is involved in 2 Hz but not 100 Hz electroacupuncture analgesia at spinal level.
Chapter
The most frequent injury of the musculoskeletal system is the lateral ankle sprain. One would suppose that, for such a common injury, a uniform assessment and treatment scheme would be available and accepted. However, this is not the case. Treatment recommendations range from almost neglect to early surgical repair.
Chapter
Acupuncture was commonly performed in China to achieve pain relief before it attracted special interest in the late 1950s as a result of its use for anesthetic purposes in surgical operations. In the excitement aroused by this unexpected new application of the ancient healing technique, numerous scientists were recruited to undertake scientific exploration of its basic mechanisms. At the first “All-China Conference on Acupuncture Anesthesia” held in Shanghai in 1965 more than 100 papers were presented; due consideration was given to the basic phenomenon of acupuncture analgesia (AA) in humans (Research Group of AA, Peking Medical College 1973), attention being drawn to its slow onset (an induction period of 20–30min) and slow decay (half-life of 16min).
Article
Pain is the major complaint of the estimated one million U.S. consumers who use acupuncture each year. Although acupuncture is widely available in chronic pain clinics, the effectiveness of acupuncture for chronic pain remains in question. Our aim was to assess the effectiveness of acupuncture as a treatment for chronic pain within the context of the methodological quality of the studies. MEDLINE (1966-99), two complementary medicine databases, 69 conference proceedings, and the bibliographies of other articles and reviews were searched. Trials were included if they were randomized, had populations with pain longer than three months, used needles rather than surface electrodes, and were in English. Data were extracted by two independent reviewers using a validated instrument. Interrater disagreements were resolved by discussion. Fifty one studies met inclusion criteria. Clinical heterogeneity precluded statistical pooling. Results were positive in 21 studies, negative in 3 and neutral in 27. Three fourths of the studies received a low-quality score and low-quality trials were significantly associated with positive results (p = 0.05). High-quality studies clustered in designs using sham acupuncture as the control group, where the risk of false negative (type II) errors is high due to large sample size requirements. Six or more acupuncture treatments were significantly associated with positive outcomes (p = 0.03) even after adjusting for study quality. We conclude there is limited evidence that acupuncture is more effective than no treatment for chronic pain; and inconclusive evidence that acupuncture is more effective than placebo, sham acupuncture or standard care. However, we have found an important relationship between the methodology of the studies and their results that should guide future research.
Article
This chapter begins by briefly placing modem acupuncture in an historical context. This leads, in the following section, to a discussion of some technical difficulties and limitations of experimental paradigms for the study of the clinical efficacy of acupuncture. Then, in order to provide a background for understanding the biological underpinnings of the clinical effects of acupuncture, it undertakes a brief review of selected aspects of the literature concerned with the evaluation of the clinical efficacy of acupuncture as a treatment modality for various medical ailments. The discussion of biological mechanisms involved in acupuncture discusses on the analgesic effects of acupuncture, because little is known about the biological foundation of other acupuncture effects. The analysis of acupuncture analgesia examines the data from both man and other animals. The data from man is restricted primarily to evidence indicating a role for endogenous opioids, and these data are assessed in detail. There is also extensive evidence for a role of endogenous opioids in animal models of acupuncture analgesia. These data are discussed as well as data indicating a role for additional neural mechanisms.
Article
Objective.— To provide clinicians, patients, and the general public with a responsible assessment of the use and effectiveness of acupuncture to treat a variety of conditions.Participants.— A nonfederal, nonadvocate, 12-member panel representing the fields of acupuncture, pain, psychology, psychiatry, physical medicine and rehabilitation, drug abuse, family practice, internal medicine, health policy, epidemiology, statistics, physiology, biophysics, and the representatives of the public. In addition, 25 experts from these same fields presented data to the panel and a conference audience of 1200. Presentations and discussions were divided into 3 phases over 212 days: (1) presentations by investigators working in areas relevant to the consensus questions during a 2-day public session; (2) questions and statements from conference attendees during open discussion periods that were part of the public session; and (3) closed deliberations by the panel during the remainder of the second day and morning of the third. The conference was organized and supported by the Office of Alternative Medicine and the Office of Medical Applications of Research, National Institutes of Health, Bethesda, Md.Evidence.— The literature, produced from January 1970 to October 1997, was searched through MEDLINE, Allied and Alternative Medicine, EMBASE, and MANTIS, as well as through a hand search of 9 journals that were not indexed by the National Library of Medicine. An extensive bibliography of 2302 references was provided to the panel and the conference audience. Expert speakers prepared abstracts of their own conference presentations with relevant citations from the literature. Scientific evidence was given precedence over clinical anecdotal experience.Consensus Process.— The panel, answering predefined questions, developed their conclusions based on the scientific evidence presented in the open forum and scientific literature. The panel composed a draft statement, which was read in its entirety and circulated to the experts and the audience for comment. Thereafter, the panel resolved conflicting recommendations and released a revised statement at the end of the conference. The panel finalized the revisions within a few weeks after the conference. The draft statement was made available on the World Wide Web immediately following its release at the conference and was updated with the panel's final revisions within a few weeks of the conference. The statement is available at http://consensus.nih.gov.Conclusions.— Acupuncture as a therapeutic intervention is widely practiced in the United States. Although there have been many studies of its potential usefulness, many of these studies provide equivocal results because of design, sample size, and other factors. The issue is further complicated by inherent difficulties in the use of appropriate controls, such as placebos and sham acupuncture groups. However, promising results have emerged, for example, showing efficacy of acupuncture in adult postoperative and chemotherapy nausea and vomiting and in postoperative dental pain. There are other situations, such as addiction, stroke rehabilitation, headache, menstrual cramps, tennis elbow, fibromyalgia, myofascial pain, osteoarthritis, low back pain, carpal tunnel syndrome, and asthma, in which acupuncture may be useful as an adjunct treatment or an acceptable alternative or be included in a comprehensive management program. Further research is likely to uncover additional areas where acupuncture interventions will be useful.
Article
Rabbits have been used for the study of the mechanisms of acupuncture analgesia in several laboratories over the world. Its feasibility was, however, questioned by Galeano et al. in two recent papers published in this journal. In the present study experimental details are presented for the induction of analgesia by electroacupuncture (EA) in the rabbit. A total of 219 experiments were performed in 47 adult rabbits. Latency of avoidance response (ARL) elicited by radiant heat exposure on the skin over the snout or the tail was taken as the index of nociception, the efficacy of which was verified by the constancy of the ARL over the period of observation and the dose-dependent increase of ARL after morphine injection. EA stimulation of the Zusanli and Quenlun points in one hind leg for 10 min brought about an intensity-dependent increase of ARL by 127, 155 and 170% on the snout and a comparable increase on the tail in groups of rabbits receiving 0.5, 1 and 2 V EA stimulation respectively. The increased ARL faded away exponentially after the cessation of EA with half-lives of 10, 11 and 13 min in the aforementioned 3 groups of animals. The effects were found to be partially blocked by intracerebroventricular injections of naloxone. It is concluded that under optimal conditions intensity-dependent and reproducible EA analgesia can be elicited in rabbits without visible agitation or frightened responses.
Article
We studied the effect of NAN-190 (5-HT1A antagonist), ketanserin (5-HT2 antagonist) and ICS 205-930 (5-HT3 antagonist) on tooth pulp stimulation (TPS)-induced 5-HT release and substance P (SP) release in the superficial layers of the trigeminal nucleus caudalis (SpVc-I,II) in the presence or absence of electro-acupuncture (EAP). TPS slightly increased 5-HT release and significantly increased SP release. In combination with EAP, TPS-induced 5-HT release was remarkably enhanced, whereas SP release was significantly suppressed. Pretreatment with NAN-190 (3.5 mg/kg, i.v.) significantly enhanced the increase in TPS-induced 5-HT release in the presence of EAP. On the other hand, the increase of 5-HT release induced following TPS in the presence of EAP was inhibited by pretreatment with ketanserin (2.5 mg/kg, i.v.) and ICS 205-930 (1 mg/kg, i.v.). When NAN-190 was pre-treated in the animals combined TPS and EAP, the amount of SP release was significantly reduced compared with the absence of this drug. On the other hand, pretreatment with ketanserin and ICS 205-930 reversed the inhibitory effect of EAP on the TPS-generated SP release, especially ICS 205-930, which remarkably enhanced TPS-induced SP release compared with the absence of this drug. On the basis of the obtained results, we concluded that NAN-190 and ICS 205-930 act on EAP-induced analgesia positively and suppressively, respectively, by regulation of TPS-generated SP release through activation of their subtype receptors. On the other hand, ketanserin does not affect TPS-induced 5-HT release and SP release in the presence of EAP.
Article
(1) The characteristics of an analgesia which can be elicited in rabbits by electrically activated acupuncture needles are described. (2) The analgesia can be reversed by systemic administration of the inhibitory amino acid antagonists bicuculline or strychnine. (3) Pharmacological procedures which interfere with tryptaminergic mechanisms, or destruction of the dorsal raphe nuclei, prevent the development of analgesia. (4) It is concluded that the production of analgesia probably depends upon postsynaptic inhibition of the transmission of afferent information from nociceptors, and at more than one site in the central nervous system.
Article
This present paper shows different levels of electroacupuncture analgesia (antinociceptive effect) induced by three different frequencies of stimulation (i.e. 0.2, 4 and 200 Hz); highest analgesia is induced at 200 Hz and lowest at 0.2 Hz. Naloxone (1 mg/kg) completely reverses the electroacupuncture effects at low frequency stimulation (4 Hz) but produces no inhibition at high frequency stimulation (200 Hz). Conversely, parachlorophenylalanine (320 mg/kg) partially blocks the high-frequency (200 Hz) analgesia but produces no effect on the low-frequency (4 Hz) electroacupuncture analgesia. This suggests that electroacupuncture analgesia induced by low frequency stimulation may be mediated by endorphins while high frequency stimulation is not endorphinergic but may be partly due to serotonin.
Article
Electroacupuncture in awake mice produced analgesia to noxious heat stimuli causing a 54% increase in latency to squeak. Subcutaneous naloxone completely abolished this acupuncture analgesia implicating endorphin. Naloxone injections in control mice caused a 17% hyperalgesia suggesting that “normal” mice also release endorphin. These results imply that endorphin is released at a low basal rate in “normal” mice, and at a much higher rate during acupuncture.
Article
Conditioning electrical stimulation of peripheral nerves is presently routinely employed for alleviation of chronic pain in humans. Most commonly, high frequency stimulation of probably mainly coarse myelinated afferents from the skin is used as proposed in the gate theory of Melzack and Wall25. However, only a limited number of patients benefit from such stimulation. To improve the results of such treatment we have developed a kind of acupuncture-like electrical stimulation where mixed nerves are stimulated with short trains of stimuli given at a slow repetition rate via surface electrodes to elicit muscle contractions. The compiled results of conditioning stimulation for analgesia were then markedly improved.To see whether the analgesia experienced by the chronic pain patients is mediated via links utilizing endorphins, the opiate antagonist naloxone was administered to these patients under double-blind conditions, saline being used as a placebo. We then found that 6 out of 10 patients receiving acupuncture-like stimulation but none out of 10 patients receiving high frequency stimulation of skin nerves, reported an inhibition of the stimulation-produced analgesia by naloxone. This indicates that the analgesia produced by acupuncture-like stimulation is mediated via mechanisms utilizing endorphins whereas the analgesia produced from high frequency stimulation of coarse cutaneous afferents is mediated via some other mechanism.
Article
The analgesic effect induced by 2/15 Hz electroacupuncture as shown by the increase in tail flick latency decreased steadily as electroacupuncture stimulation was given continuously for 6 h, showing the development of tolerance to electroacupuncture analgesia. These rats were then given an intrathecal (i.t.) injection of one of the following opioid agonists: the mu agonist, ohmefentanyl 7.5, 15 and 30 pmol, 10 min apart; the delta agonist, [D-Pen2,D-Pen5]enkephalin (DPDPE) 5, 10 and 20 nmol, 10 min apart and the kappa agonist, dynorphin-(1-13) 2.5, 5 and 10 nmol, 10 min apart, respectively. The analgesic effect induced by ohmefentanyl, DPDPE or dynorphin was dramatically reduced in rats rendered tolerant to 2/15 Hz electroacupuncture analgesia. Rats were injected i.t. with one of the three specific opioid antagonists: the mu antagonist, beta-funaltrexamine (beta-FNA) (5, 10 and 20 nmol), the delta antagonist, ICI174,864 (1, 2 and 4 nmol) and the kappa antagonist, nor-binaltorphimine (nor-BNI) (3.125, 6.25 and 12.5 nmol). It was found that analgesia induced by 2/15 Hz electroacupuncture stimulation was significantly and almost totally blocked by any one of the three opioid antagonists. These results suggest that all three types of opioid receptors, the mu, delta and kappa receptors in the spinal cord of the rat play important roles in mediating analgesia induced by electroacupuncture of 2/15 Hz.
Article
The cross-tolerance technique was used to analyze the receptor mechanisms of analgesia induced by electroacupuncture (EA) of 2 Hz, 100 Hz, or 2-15 Hz. (1) Rats were given EA stimulation of 2 Hz, 100 Hz and 2-15 Hz for 30 min with 30 min intervals successively. The percentage increase in tail-flick latency (TFL) was taken to indicate the intensity of EA analgesia. Rats made tolerant to repeated intrathecal injection of the mu-opioid agonist ohmefentanyl (OMF, 15 pmol, Q2h x 5) or the delta-opioid agonist DPDPE (10 nmol, Q2h x 5) showed a cross tolerance to both 2 Hz- and 2-15 Hz-, but not to 100 Hz-EA analgesia; and rats made tolerant to kappa-opioid agonist dynorphin-(1-13) (5 nmol, Q2h x 5) showed a cross-tolerance to 100 Hz- and 2-15 Hz-, but not to 2 Hz-EA analgesia; (2) Rats made tolerant to 2-15 Hz EA showed cross-tolerance to either 2 Hz- or 100 Hz-EA analgesia; (3) Rats made tolerant to either 2 Hz- or 100 Hz-EA were still reactive to 2-15 Hz-EA. The results indicate that 2 Hz-EA analgesia is mediated by mu- and delta-receptors, 100 Hz-EA analgesia by kappa-receptor, and 2-15 Hz-EA analgesia by combined action of mu-, delta- and kappa-receptors in the spinal cord of the rats.
Article
Increases in neuronal activity in response to tissue injury lead to changes in gene expression and prolonged changes in the nervous system. These functional changes appear to contribute to the hyperalgesia and spontaneous pain associated with tissue injury. This activity-dependent plasticity involves neuropeptides, such as dynorphin, substance P and calcitonin gene-related peptide, and excitatory amino acids, such as NMDA, which are chemical mediators involved in nociceptive processing. Unilateral inflammation in the hindpaw of the rat results in an increase in the expression of preprodynorphin and preproenkephalin mRNA in the spinal cord, which parallels the behavioral hyperalgesia associated with the inflammation. Cellular intermediate-early genes, such as c-fos, are also expressed in spinal cord neurons following inflammation and activation of nociceptors. Peripheral inflammation results in an enlargement of the receptive fields of many of these neurons. Dynorphin applied to the spinal cord also induces an enlargement of receptive fields. NMDA antagonists block the hyperexcitability produced by inflammation. A model has been proposed in which dynorphin, substance P and calcitonin gene-related peptide enhance excitability at NMDA receptor sites, leading first to dorsal horn hyperexcitability and then to excessive depolarization and excitotoxicity.
Article
The descending pain inhibitory system (DPIS) associated with acupuncture analgesia (AA), caused by low frequency stimulation of an acupuncture point, was identified by the results of lesion and stimulation procedures previously determined to differentiate the afferent and efferent paths in rats. The DPIS starts in the posterior arcuate nucleus and descends to the hypothalamic ventromedian nucleus (HVM) from whence it divides into two pathways: one path, the serotonin mediated path, descends through the ventral periaqueductal central gray (V-PAG) and then to the raphe magnus (RM). The other, the noradrenaline mediated path, descends through the reticuloparagigantocellular nucleus (NRPG) and part of the reticulogigantocellular nucleus (NRGC). The afferent and efferent paths are both present in the RM and NRGC, and were separately identified by means of the analgesia (SPA) produced by stimulation of the separate regions in AA responders and nonresponders, because SPA of these regions in nonresponders produced only efferent pathway mediated analgesia.
Article
Low frequency electroacupuncture (EA) analgesia has been thought to be mediated by endogenous opioids. Among other lines of evidence, it has been reported that EA stimulation delivered at 2 and 2-15 Hz in rats could be blocked or partially antagonized by naloxone (NAL) and naltrexone (NTX). In contrast, experiments in one of our laboratories (D.J.M.) showed that NAL did not inhibit 2 Hz, and even potentiated 125 Hz EA analgesia. In an attempt to resolve these discrepancies, we conducted joint experiments in the U.S.A. and in China using the methods which previously yielded NAL reversibility of EA analgesia. In no experiment did opiate antagonists block or reduce EA analgesia. On the contrary, we found that, in most experiments, NAL and NTX potentiated 2 and 2-15 Hz EA analgesia respectively. The potentiation occurred independently of laboratory methods, geographic location of the experiment, strain (Chinese or American), tail temperature, sex, and weight of rats. This potentiation suggests the existence of an opioid anti-analgesic system or that NAL and NTX acquired analgesic properties following EA. These results indicate that EA analgesia in rats is a variable phenomenon even when laboratory methods are rigorously replicated. The EA stimulation may activate multiple conflicting neural circuits which interact and ultimately modulate the analgesic outcome.
Article
Arthritis was induced in ether anesthetised rats by injecting 1.25 mg of sodium urate crystals into the ankle joint. Twenty-four hr after the injection the ankle is swollen and the animal does not place full weight on the affected foot. The ankle is more sensitive than normal to movement and pressure. Responses to stimulation of the foot and toes on the arthritic limb are reduced due to a reluctance to move the affected limb. These measures, which reflect ongoing pain, hyperalgesia or tenderness and guarding, are attenuated in animals treated with dexamethasone, phenylbutazone, and morphine, as well as in animals whose nerves to the ankle had been pretreated with capsaicin. Guanethidine and colchicine failed to influence the behavioural responses to the urate injection. Ankle joint urate arthritis has advantages over other models of arthritis for therapeutic testing in that in a short time it affects a single joint in rats, and it produces responses which can be assessed by simple, sensitive measures.
Article
An animal model for tonic pain has been produced by means of injecting monosodium urate crystals into a knee joint of rat hind paws in order to evaluate the analgesic effects of various drugs and analgesic methods and to elucidate the physiology of tonic pain. This model allows for stable and long-term behavioural changes due to tonic pain followed by complete recovery without tissue damages. It is advantageous in allowing for objective and quantitative evaluation of the effects of analgesics and should prove useful in research on pain and the development of pain therapy techniques. Using this model, the analgesic effects of capsaicin was evaluated when administered to the neonatal rat or locally to peripheral nerves. In both cases, significant analgesic effects were obtained.
Article
We studied the effects of systemic injections of monoamine depletors, enhancers or receptor blockers on electroacupuncture analgesia (EAA) in mice. The following results emerged. (i) EAA is reduced by depletors of monoamines (tetrabenazine, TBZ depletes all monoamines; para-chlorophenylalanine, PCPA depletes serotonin; alpha-methyl-para-tyrosine, AMPT depletes catecholamines). However, depletion of noradrenaline and increase of serotonin by disulfiram enhances EAA. (ii) Replacement of depleted monoamines after TBZ treatment by their precursors (5-HTP or L-DOPA) restores EAA. (iii) EAA is enhanced by potentiating serotonin and dopamine by probenecid. EAA is also enhanced by the administration of monoamine precursors (L-DOPA for dopamine, 5-HTP for serotonin). The dopamine receptor stimulator, apomorphine, reduces EAA. (iv) EAA is also reduced by receptor blockade of catecholamines (by haloperidol), or blockade of noradrenaline (by yohimbine) or serotonin (by cinanserin). However, blockade of dopamine by pimozide has no significant effect on EAA. There are two main conclusions: (i) EAA results are similar to those previously reported for SPA for all drugs except apomorphine and pimozide; and (ii) EAA shows consistent results only with manipulations of serotonin: the data indicating that EAA (at 200 Hz) is mediated by serotonin. Since previous studies show that raphe or DLF (dorsolateral fasciculus) lesions abolish EAA, we postulate that descending axons from raphe release serotonin to inhibit trigeminal or spinal cord nociception during EAA.
Article
Electroacupuncture (EA), a form of transcutaneous electrical stimulation, produces opiate-like antinociception and catalepsy in rats. This effect of EA cannot be produced in hypophysectomised rats, whereas adrenalectomised rats show increased sensitivity. In intact rats, adrenocorticotrophic hormone and dexamethasone have been found to be effective to sensitise the animals to the analgesic effect of EA. Deoxycorticosterone, on the contrary, attenuates this effect. Spironolactone is also effective to potentiate EA response, which is accompanied with severe respiratory depression. Drugs that are known to affect adrenal aldosterone secretion also modulate the effect of EA. Naloxone administration, 15 min prior to the initiation of EA stimulation, potentiates the effect of EA, whereas it counteracts the effect of EA if administered after initiation of EA stimulation. Moreover, this counteracting ability of naloxone increases with the increase in time interval between initiation of stimulation and naloxone challenge. Pretreatment with drugs that impair adrenal mineralocorticoid response to physiological stimuli inhibits the counteracting effect of naloxone. On the contrary, mineralocorticoid supplemented rats show greater sensitivity to naloxone counteraction.
Article
The basis for using narcotic antagonists for the treatment of opiate addiction is discussed briefly, and the chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of naltrexone hydrochloride, an opiate antagonist drug, are reviewed. Naltrexone is rapidly and completely absorbed after oral administration but undergoes substantial first-pass extraction and metabolism by the liver. Naltrexone has a half-life of 3.9-10.3 hours and a slow terminal elimination-phase half-life of 96 hours. The major metabolite of naltrexone is 6-beta-naltrexol, which is present in plasma in greater concentrations than the parent drug. Problems in study design and patient adherence to treatment have made assessment of naltrexone's clinical efficacy difficult; however, studies have consistently demonstrated that patients who remained off opiates longer were those who took naltrexone longer. Factors associated with successful treatment outcomes include sustained therapy with naltrexone, participation in multidisciplinary programs of behavioral therapy and psychotherapy, and good family and social support systems. Gastrointestinal irritation and, in some studies, clinically insignificant increases in blood pressure, have been the most common adverse effects. Currently available data suggest that naltrexone is a very safe drug. The usual dosage of naltrexone hydrochloride is 50 mg orally once daily or 350 mg orally per week in three divided doses. Patients should be detoxified and opiate free for two to five days before initiation of naltrexone therapy. Naltrexone appears to be a useful adjunct to therapy in opiate addicts who are well motivated and who have strong psychological support systems.
Article
We were unable to demonstrate the reversal of dental acupunctural analgesia following the injection of 0.4 mg naloxone using evoked potential methodology. Since our findings differed from those of Mayer, Price and Rafii who used pain threshold methods, we attempted to replicate their study. Subjects who demonstrated acupunctural analgesia during electrical stimulation of the LI-4 point on the hands received either 1.2 mg naloxone or normal saline under double blind conditions. Pain thresholds elevated by acupuncture failed to reverse when naloxone was given. Review of experimental design issues, other related human subjects research, and animal studies on acupunctural analgesia provided little convincing evidence that endorphins play a significant role in acupunctural analgesia. Because endorphins can be released in response to a stressor, endorphin presence sometimes correlates with acupunctural treatment in animal studies and some human studies, especially those involving pain patients. The primary analgesia elicited by acupunctural stimulation seems to involve other mechanisms.
Article
The effects of electrical acupunctural stimulation (2 Hz) on pain judgments and evoked potentials are reported for two experiments using dental dolorimetry. In the first experiment subjects received acupuncture at points located in the same neurologic segment as the test tooth. In the second experiment subjects received acupuncture at points on the hands located on acupuncture meridians. In both instances acupuncture resulted in a reduction in pain intensity and smaller evoked potential amplitudes, but naloxone neither reversed the analgesia nor did it affect the evoked potentials. A pilot study was carried out to determine whether manual rather than electrical stimulation would produce an analgesia reversible by naloxone, but it failed to do so. These findings contribute to the growing evidence that acupunctural stimulation significantly reduces pain sensibility in volunteers undergoing dolorimetric testing, but they do not support the hypothesis that endorphin release is a mechanism by which acupuncture exerts analgesia.
Article
Chronic pain is characterized by abnormal sensitivity, which is due to the generation of pain in response to the activation of the low-threshold mechanoreceptive A beta fibres that normally generate innocuous sensations. Three different processes in the spinal cord can account for this dramatic alteration in sensory processing in the somatosensory system: increased excitability, decreased inhibition and structural reorganization. All have been shown to occur and each may contribute separately or together to the wide range of chronic inflammatory and neuropathic pain disorders. The unravelling of the cellular mechanisms involved both offers the potential for developing novel therapeutic strategies, which reduce functional synaptic plasticity and prevent central atrophic and regenerative responses in injured neurones, and illustrates the capacity of the adult nervous system for maladaptive modification.
This study compares two methods for evaluating pain-related behavior in an animal model with carrageenan-induced monoarthritis. Rats injected with lambda-carrageenan into the right tibio-tarsal joint were videofilmed at various times after injection and later scored regarding their stance. Immediately after each videorecording session the animals were tested in a box constructed to register the weight load exerted by the hindpaws by means of force plates inserted in the floor. Following carrageenan injection (300 micrograms in 50 microL) the load on the injected paw fell from a control value of 39.3% +/- 0.4% of the body weight (mean +/- SEM, n = 6) to a minimum of 5.1% +/- 1.8% at 6 hr and then slowly increased to approach control levels at 72 hr. The weight load on the contralateral paw increased from a control value of 38.9% +/- 0.6% to 52.4% +/- 1.4% at 6 hr, whereafter it gradually decreased. The video-based stance scores also showed a maximal impairment at 4-6 hr, with a gradual return towards control values at 72 hr. However, the results based on the force plate measurements were less variable and more graded. Morphine inhibited the carrageenan-induced effect in a dose-dependent manner in both paradigms. In conclusion, the present results indicate that measurement of weight bearing as described in the present paper is a practical, useful, and objective method to assess the degree of arthritic pain in the rat.
Article
Many people use unconventional therapies for health problems, but the extent of this use and the costs are not known. We conducted a national survey to determine the prevalence, costs, and patterns of use of unconventional therapies, such as acupuncture and chiropractic. We limited the therapies studied to 16 commonly used interventions neither taught widely in U.S. medical schools nor generally available in U.S. hospitals. We completed telephone interviews with 1539 adults (response rate, 67 percent) in a national sample of adults 18 years of age or older in 1990. We asked respondents to report any serious or bothersome medical conditions and details of their use of conventional medical services; we then inquired about their use of unconventional therapy. One in three respondents (34 percent) reported using at least one unconventional therapy in the past year, and a third of these saw providers for unconventional therapy. The latter group had made an average of 19 visits to such providers during the preceding year, with an average charge per visit of $27.60. The frequency of use of unconventional therapy varied somewhat among socio-demographic groups, with the highest use reported by nonblack persons from 25 to 49 years of age who had relatively more education and higher incomes. The majority used unconventional therapy for chronic, as opposed to life-threatening, medical conditions. Among those who used unconventional therapy for serious medical conditions, the vast majority (83 percent) also sought treatment for the same condition from a medical doctor; however, 72 percent of the respondents who used unconventional therapy did not inform their medical doctor that they had done so. Extrapolation to the U.S. population suggests that in 1990 Americans made an estimated 425 million visits to providers of unconventional therapy. This number exceeds the number of visits to all U.S. primary care physicians (388 million). Expenditures associated with use of unconventional therapy in 1990 amounted to approximately $13.7 billion, three quarters of which ($10.3 billion) was paid out of pocket. This figure is comparable to the $12.8 billion spent out of pocket annually for all hospitalizations in the United States. The frequency of use of unconventional therapy in the United States is far higher than previously reported. Medical doctors should ask about their patients' use of unconventional therapy whenever they obtain a medical history.
Article
Previous studies in rats measuring latency to tail flick with radiant heat have shown that the antinociceptive effect induced by electrical stimulation of different frequencies at traditional acupuncture sites is mediated via different opioid receptors in the spinal cord. The present study was designed to observe (1) whether electrical stimulation at such sites could produce antinociceptive effects in the cold water tail-flick (CWT) test; (2) whether the antinociceptive effects could be blocked by s.c. injection of the opioid receptor antagonist naloxone and (3) whether i.c.v. injection of selective antagonists for mu (cyclic D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2, CTAP), delta (naltrindole) or kappa (nor-binaltorphimine) opioid receptors would block the antinociceptive effect produced by electrical stimulation. Sprague-Dawley rats were stimulated at frequencies of 2, 30 or 100 Hz with acupuncture needles inserted into acupoints Zusanli and Sanyinjiao in the hind leg for 30 min. Antinociception was assayed in the CWT. The results showed that (1) a significant, frequency-related increase in threshold in the CWT was observed in all electrical stimulation groups as compared with the placebo group and the antinociceptive effect lasted about 30 min poststimulation; (2) naloxone (s.c.) antagonized the antinociceptive effect induced by 2 Hz, 30 Hz or 100 Hz electrical stimulation and (3) either CTAP or naltrindole (i.c.v.) almost completely blocked the antinociceptive effect induced by 2 Hz or 30 Hz electrical stimulation, but was less effective in blocking antinociception induced by 100 Hz electrical stimulation; nor-binaltorphimine (i.c.v.) greatly reduced antinociception induced by 30 Hz or 100 Hz electrical stimulation, but not by 2 Hz electrical stimulation. These results indicate that the antinociception induced by 2 Hz electrical stimulation is mediated by both mu and delta opioid receptors; the antinociception induced by 100 Hz electrical stimulation is mediated primarily by the kappa receptor; and the antinociception induced by 30 Hz electrical stimulation is mediated by all three opioid receptor types. Thus, the antinociceptive effect induced by peripheral electrical stimulation, as measured by the CWT, involves opioid receptors in the rat brain.
Article
Acupuncture is an ancient Chinese method to treat diseases and relieve pain. We have conducted a series of studies to examine the mechanisms of this ancient method for pain relief. This article reviews some of our major findings. Our studies showed that acupuncture produces analgesic effect and that electroacupuncture (EA) is more effective than manual acupuncture. Furthermore, electrical stimulation via skin patch electrodes is as effective as EA. The induction and recovering profiles of acupuncture analgesia suggest the involvement of humoral factors. This notion was supported by cross-perfusion experiments in which acupuncture-induced analgesic effect was transferred from the donor rabbit to the recipient rabbit when the cerebrospinal fluid (CSF) was transferred. The prevention of EA-induced analgesia by naloxone and by antiserum against endorphins suggests that endorphins are involved. More recent work demonstrated the release of endorphins into CSF following EA. In addition, low frequency (2 Hz) and high frequency (100 Hz) of EA selectively induces the release of enkephalins and dynorphins in both experimental animals and humans. Clinical studies suggesting its effectiveness for the treatment of various types of pain, depression, anxiety, spinally induced muscle spasm, stroke, gastrointestinal disorders, and drug addiction were also discussed.
Article
This article reports the results of a survey of acupuncture practice in chronic pain clinics in the United Kingdom. The survey reveals that acupuncture is widely used in the treatment of chronic pain with 84% of those responding stating that is was available at their clinics. The majority of practitioners had attended a course at one of the 'acupuncture schools' but in about one fifth of the clinics the practitioner had not received any formal training.
Article
Pain is the major complaint of the estimated one million U.S. consumers who use acupuncture each year. Although acupuncture is widely available in chronic pain clinics, the effectiveness of acupuncture for chronic pain remains in question. Our aim was to assess the effectiveness of acupuncture as a treatment for chronic pain within the context of the methodological quality of the studies. MEDLINE (1966-99), two complementary medicine databases, 69 conference proceedings, and the bibliographies of other articles and reviews were searched. Trials were included if they were randomized, had populations with pain longer than three months, used needles rather than surface electrodes, and were in English. Data were extracted by two independent reviewers using a validated instrument. Inter-rater disagreements were resolved by discussion. Fifty one studies met inclusion criteria. Clinical heterogeneity precluded statistical pooling. Results were positive in 21 studies, negative in 3 and neutral in 27. Three fourths of the studies received a low-quality score and low-quality trials were significantly associated with positive results (P=0.05). High-quality studies clustered in designs using sham acupuncture as the control group, where the risk of false negative (type II) errors is high due to large sample size requirements. Six or more acupuncture treatments were significantly associated with positive outcomes (P=0.03) even after adjusting for study quality. We conclude there is limited evidence that acupuncture is more effective than no treatment for chronic pain; and inconclusive evidence that acupuncture is more effective than placebo, sham acupuncture or standard care. However, we have found an important relationship between the methodology of the studies and their results that should guide future research.
Article
Endomorphin-1 is a novel endogenous mu-opioid peptide. In this study, we examined the effects of 2 Hz electroacupuncture in the rat tail flick test and the formalin test (a persistent noxious model). Moreover, we investigated if the electroacupuncture potentiated the effect of intrathecal endomorphin-1. The results demonstrated that electroacupuncture alone produced a significant antinociception in the tail flick test, but not in the formalin test, and that intrathecal endomorphin-1 dose-dependently suppressed the biphasic nociceptive behavior in the formalin test. Electroacupuncture enhanced the antinociceptive effect of intrathecal endomorphin-1 in the formalin test, resulting in a significant leftward shift in the dose-response curves for intrathecal endomorphin-1 antinociception. The enhanced effect was antagonized by intraperitoneal naltrexone. The study suggests that electroacupuncture may potentiate the intrathecal endomorphin-1 antinociception partially mediated by opioid receptors.
Article
Since pain is an important symptom in arthritis, useful behavioral indices for pain in experimental arthritis animal models are important tools for investigative work on arthritis. The purpose of this study was to develop simple and quantifiable behavioral tests, which would represent the level of arthritic pain that develops after induction of inflammation in the knee. Two models of knee joint arthritis were produced: (1) KC model-injection of kaolin and carrageenan into the synovial cavity of the knee, and (2) CFA model-injection of complete Freund's adjuvant into the synovial cavity of the knee. The following three variables were measured before and at various times after the induction of arthritis. As an estimate of the degree of edema, the circumference of the knee was measured. As pain indices, (1) the vocalization threshold of compression force applied to the knee joint was measured to represent tenderness of the joint, and (2) the struggle threshold of the knee extension angle was measured to represent a reduction in range of motion in the arthritic joint. A time course study showed that behavioral changes last for at least 1 week for the KC model and at least 2 weeks for the CFA model. Correlation studies showed that all three variables significantly correlated with each other in both the KC and CFA arthritic models. Systemically injected morphine produced a partial reversal of these indices with the expected time course and dose response of a morphine-induced analgesic. It is concluded that two variables, the struggle threshold for knee extension and the vocalization threshold for knee compression, could be used as simple and useful pain indices in experimental models of arthritis.
NIH Consensus Development Panel. Acupuncture
NIH Consensus Development Panel. Acupuncture. J Am Med Assoc 1998P;280:1518–1524.
Acupuncture and stimulation produced analgesia Handbook of experimental pharmacology , 104-Opioids I
  • Js Han
Han JS. Acupuncture and stimulation produced analgesia. In: Born GVR, Cuatrecasas P, Herken H, editors. Handbook of experimental pharmacology, 104-Opioids I, Berlin: Springer, 1993. pp. 105–125.
Primary care orthopedics
  • S R Brier
Brier SR. Primary care orthopedics,. St. Louis, MO: Mosby, 1999 p. 380-6.