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ABSTRACT: BACKGROUND: Aim of the current meta-analysis was to assess the effects of intraoperative dexmedetomidine on postoperative pain, analgesic consumption, and adverse events in comparison with placebo or opioids in children undergoing surgery. METHODS: This meta-analysis was performed according to the recommendations of the PRISMA statement and the Cochrane collaboration. For dichotomous and continuous outcomes of efficacy and adverse events, the Revman(®) (The Nordic Cochrane Centre, Copenhagen, Denmark) statistical software was used to calculate relative risk (RR), mean difference (MD), and 95% confidence intervals (CI). RESULTS: We included 11 randomized controlled trials - 434 children received dexmedetomidine, 440 received control. In comparison with placebo, children receiving dexmedetomidine showed a reduced RR for postoperative opioids (0.4; 95% CI: 0.26-0.62; P < 0.00001) and postoperative pain (0.51; 95% CI: 0.32-0.81; P = 0.004). Similar results were obtained for the comparison with intraoperative opioids: reduced RR for postoperative pain (0.49; 95% CI: 0.25-0.94; P = 0.03) and the need for postoperative opioids (0.77; 95% CI: 0.60-1.09; P = 0.05). CONCLUSIONS: This meta-analysis revealed a lower risk for postoperative pain and the need for postoperative opioids following intraoperative dexmedeto-midine in comparison with placebo or opioids in children undergoing surgery; however, the influence of dexmedetomidine on postoperative opioid consumption is less clear. Although there were only a limited number of adverse events, further studies focusing on procedure specific dexmedetomidine dosing and adverse events are urgently needed.
Pediatric Anesthesia 10/2012; · 2.10 Impact Factor
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ABSTRACT: Postoperative pain treatment is an important healthcare issue. However, the management of pain in patients after surgery remains insufficient. In the present review, several key areas important for postoperative pain management are discussed. New findings about efficacy and side effects of nonopioid analgesics, such as paracetamol, NSAIDs and COX-2 inhibitors, are presented and discussed in light of acute, short-term application in the perioperative period. Second, new findings about postoperative pain management in patients with preoperative pain and chronic opioid consumption are reported. Third, feasibility of the transversus abdominal plane block as a new and promising regional anesthesia technique is discussed. Finally, potential predictors, mechanisms and preventive treatment strategies of persistent chronic pain after surgery are presented.
Expert Review of Neurotherapeutics 05/2012; 12(5):587-600.
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ABSTRACT: Clonidine is still the most popular additive for caudal regional anesthesia. Aim of the present quantitative systematic review was to assess the efficacy and safety of the combined use of clonidine and local anesthetics in comparison with caudal local anesthetics alone.
The systematic search, data extraction, critical appraisal and pooled analysis were performed according to the PRISMA statement. The systematic search included the Central register of controlled trials of the Cochrane Library (to present), MEDLINE (1966 to present), EMBASE (1980 to present) and CINAHL (1981 to present). Relative risk (RR), mean difference (MD) and the corresponding 95% confidence intervals (CI) were calculated using the Revman(®) statistical software for dichotomous and continuous outcomes.
Twenty randomized controlled trials (published between 1994 and 2010) including 993 patients met the inclusion criteria. There was a longer duration of postoperative analgesia in children receiving clonidine in addition to local anesthetic (MD: 3.98 h; 95% CI: 2.84-5.13; P < 0.00001). Furthermore, there was a lower number of patients requiring rescue analgesics in the clonidine group (RR: 0.72; 95% CI: 0.57-0.90; P = 0.003). The incidence of complications (e.g., respiratory depression) remained very low and was not different to caudal local anesthetics alone.
There is considerable evidence that caudally administered clonidine in addition to local anesthetics provides extended duration of analgesia with a decreased incidence for analgesic rescue requirement and little adverse effects compared to caudal local anesthetics alone.
Pediatric Anesthesia 12/2011; 21(12):1219-30. · 2.10 Impact Factor
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ABSTRACT: Gender differences in pain modulation are evident but data are rare with regard to perioperative regional analgesia. The aim of the present analysis was to assess gender-related differences in pain ratings, analgesic consumption, and adverse events in a large group of patients treated with patient-controlled epidural analgesia (PCEA) after major surgery. Data from 14,988 adult patients (6506 women; 8482 men) receiving a PCEA between January 1998 and December 2009 were examined. Demographic data and postoperative measurements assessed by the Acute Pain Service, including total PCEA consumption, pain scores, and complications, were analyzed by using PASW Statistics (18.0; SPSS Inc, Chicago, IL, USA). Beyond standard descriptive analyses, gender-related differences were investigated using a stepwise multivariate analysis of variances. Postoperative pain scores during rest and movement were almost equal between men and women. However, women showed lower total PCEA consumption consistently throughout the 5-day observation period (relative reduction by 1.7%-10.2% compared to men; P=0.00). Total PCEA consumption did not interact with surgical site (abdomen, thorax, extremity) (P=0.379) or age (<50, 50-75, >75 years; P=0.330), but was influenced by body mass index (P=0.017) and vomiting (P=0.011). Furthermore, motor blockade was greater in females compared to males (P=0.000). In patients treated with PCEA, gender differences in numeric rating scale scores exist but are not clinically relevant. However, reduced total PCEA consumption in women might be a consequence of an increased incidence of motor blockade and vomiting; the latter point towards an opioid-free PCEA solution in female patients at high risk for vomiting.
Pain 11/2011; 153(1):238-44. · 5.78 Impact Factor
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ABSTRACT: Impairment of spinal GABAergic inhibition is demonstrated to contribute to pathologic chronic pain states. We investigated spinal and peripheral GABAergic regulation of incisional pain in rats. We found that intrathecal but not peripheral administration of muscimol (GABA-A receptor agonist) and baclofen (GABA-B receptor agonist) reduced mechanical and thermal hyperalgesia after plantar incision in rats. Nonevoked pain behavior after incision was unaffected by these agonists. Similarly, nociception in unincised rats was not reduced by the same dose of agonists. Thus, GABA-A and GABA-B receptors are involved in mediating incision-induced hyperalgesia (but not nonevoked pain). Intrathecal and systemic application of L-838,417, a subtype-selective benzodiazepine site agonist (α2, α3, α5), reduced mechanical and heat hyperalgesia after incision, indicating a role of these subunits in mediating incision-induced hyperalgesia. Interestingly, the effects of all agonists were more intense and prolonged on the day after surgery than on the day of incision. Similarly, spinally administered GABA-A and GABA-B antagonists increased pain behavior, again with a greater effect 1 day after incision. One possible explanation for this finding might be that an incision modulates GABA-mediated inhibition 1 day after incision. However, expression of GABA-A receptor subunits α2 and α3 and GABA-B receptor subunits within the dorsal horn of the spinal cord were unchanged after incision, indicating that receptor expression cannot explain a possible modulation of GABAergic inhibition after incision. Thus, other mechanisms need to be considered. In conclusion, GABA-A and GABA-B receptors are promising targets for postoperative, incisional pain in humans.
Pain 11/2011; 153(1):129-41. · 5.78 Impact Factor
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Pediatric Anesthesia 10/2011; 21(10):1080-1; author reply 1081-2. · 2.10 Impact Factor
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ABSTRACT: Postoperative pain remains a challenging problem in part because the underlying mechanisms are still not well understood. There is a compelling need for translational studies in human models of postoperative pain to bridge the gap between animal models und human clinical studies.
Somatosensory changes using Quantitative Sensory Testing for up to 72 h after an experimental 4-mm incision were characterized in 20 male volunteers.
During incision, perceived pain was 29 on a 100-point numeric rating scale and declined rapidly over the next 60 min. After incision, thresholds at the site of incision were lowered to painful heat (primary heat hyperalgesia; P < 0.01, effect size: 0.68) but not to painful cold (P > 0.05, effect size: 0.00). Remote to the incision, mechanical pain thresholds were lowered, pain ratings were increased, and an area of hyperalgesia occurred (P < 0.05, effect size: 0.56; P < 0.01, effect size: 0.70; P < 0.01, respectively; secondary mechanical hyperalgesia). All signs of heat and mechanical hyperalgesia declined until full resolution at 27-72 h after incision. Increased mechanical pain ratings remote to the incision (r = 0.47; P < 0.01) but not the area of hyperalgesia (r = 0.28) or heat hyperalgesia (r = 0.12) correlated with incision-induced pain.
Ongoing activity of nociceptors underlying nonevoked pain after incision in humans may not be explained by sensitization of nociceptors to heat but triggers the increased painfulness of mechanical stimuli in the area of secondary hyperalgesia. However, the spatial expansion of hyperalgesia seems to rely on at least partly different mechanisms. These findings may contribute to the understanding of pain and hyperalgesia after surgery.
Anesthesiology 08/2011; 115(2):387-97. · 5.36 Impact Factor
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ABSTRACT: Electrical high-frequency stimulation (HFS) of skin afferents elicits long-term potentiation (LTP)-like hyperalgesia in humans. Time courses were evaluated in the facilitating (homotopic) or facilitated (heterotopic) pathways to delineate the relative contributions of early or late LTP-like pain plasticity. HFS in healthy subjects (n=55) elicited highly significant pain increases to electrical stimuli via the conditioning electrode (to 145% of control, homotopic pain LTP) and to pinprick stimuli in adjacent skin (to 190% of control, secondary hyperalgesia). Individual time courses in subjects expressing a sufficient magnitude of hyperalgesia (>20% pain increase, n=28) revealed similar half-lives of homotopic pain LTP and secondary hyperalgesia of 6.9 h and 4.9 h (log(10) mean 0.839±0.395 and 0.687±0.306) and times to full recovery of 48 h and 24 h (log(10) mean 1.679±0.790 and 1.373±0.611). Time course and peak magnitudes were not correlated between (r=-0.19to+0.21, NS), nor within both readout (r=0.29 and 0.31, NS). In most subjects, time courses were consistent with early LTP1. Notably, in some subjects (10 of 28), estimated times to full recovery were much longer (>10 days), possibly indicating development of late LTP2-like pain plasticity. Dynamic mechanical allodynia (only present in 16 of 55 subjects) lasted for a shorter time than secondary hyperalgesia. Three different readouts of nociceptive central sensitization suggest that brief intense nociceptive input elicits early LTP1 of pain sensation (based on posttranslational modifications), but susceptible subjects may already develop longer-lasting late LTP2 (based on transcriptional modifications). These findings support the hypothesis that LTP may contribute to the development of persistent pain disorders.
Pain 03/2011; 152(7):1532-9. · 5.78 Impact Factor
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ABSTRACT: In this study, the activation of different brain areas after an experimental surgical incision was assessed by functional magnetic resonance imaging, and the pathophysiological role of distinct brain activation patterns for pain perception after incision was analyzed.
Thirty male volunteers (mean age +/-SD, 25+/- 5 yr) received an experimental incision (4 mm) within the volar aspect of the right forearm using a ceramic scalper blade, and 14 volunteers (mean age +/- SD, 25 +/- 4 yr) received a sham procedure. Magnetic resonance images were taken before, during (0-2 min), and after incision or sham procedure (2-4.5, 4.5-10, 24-29, and 44-49 min) at a 3T scanner using a block design. Subjective pain ratings by a numerical pain scale were performed between the scans.
Functional magnetic resonance imaging analysis showed a distinct temporal profile of activity within specific brain regions during and after the injury. Lateralization (predominantly contralateral to the incision) and increased brain activity of the somatosensory cortex, frontal cortex, and limbic system were observed in subjects after incision, when compared with individuals receiving sham procedure. Peak brain activation occurred about 2 min after incision and decreased subsequently. A distinct correlation between evoked pain ratings and brain activity was observed for the anterior cingulate cortex, insular cortex, thalamus, frontal cortex, and somatosensory cortex.
These findings show different and distinct cortical and subcortical activation patterns over a relevant time period after incision. Pain sensitivity hereby has an influence on the activity profile. This may have important implications for encoding ongoing pain after a tissue injury, for example, resting pain in postoperative patients.
Anesthesiology 02/2010; 112(2):406-17. · 5.36 Impact Factor
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ABSTRACT: Different classes of unmyelinated nerve fibers appear to exhibit distinct conductive properties. We sought a criterion based on conduction properties for distinguishing sympathetic efferents and unmyelinated, primary afferents in peripheral nerves.
In anesthetized monkey, centrifugal or centripetal recordings were made from single unmyelinated nerve fibers in the peroneal or sural nerve, and electrical stimuli were applied to either the sciatic nerve or the cutaneous nerve endings, respectively. In centrifugal recordings, electrical stimulation at the sympathetic chain and dorsal root was used to determine the fiber's origin. In centrifugal recordings, sympathetic fibers exhibited absolute speeding of conduction to a single pair of electrical stimuli separated by 50 ms; the second action potential was conducted faster (0.61 0.16%) than the first unconditioned action potential. This was never observed in primary afferents. Following 2 Hz stimulation (3 min), activity-dependent slowing of conduction in the sympathetics (8.6 0.5%) was greater than in one afferent group (6.7 0.5%) but substantially less than in a second afferent group (29.4 1.9%). In centripetal recordings, most mechanically-insensitive fibers also exhibited absolute speeding to twin pulse stimulation. The subset that did not show this absolute speeding was responsive to chemical stimuli (histamine, capsaicin) and likely consists of mechanically-insensitive afferents. During repetitive twin pulse stimulation, mechanosensitive afferents developed speeding, and speeding in sympathetic fibers increased.
The presence of absolute speeding provides a criterion by which sympathetic efferents can be differentiated from primary afferents. The differences in conduction properties between sympathetics and afferents likely reflect differential expression of voltage-sensitive ion channels.
PLoS ONE 01/2010; 5(2):e9076. · 4.09 Impact Factor
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European Journal of Pain Supplements 01/2010; 4(1):111-111.
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ABSTRACT: Although cold hypersensitivity is a well-documented phenomenon in animals and humans with inflammatory and neuropathic pain, little is known about the presence of cold hyperalgesia after surgery. Therefore, we studied primary cold hyperalgesia after a surgical incision in mice.
Before and after plantar incision, inflammation with complete Freund adjuvant, and spared nerve ligation, unrestrained male animals were placed on a Peltier-cooled cold plate with a surface temperature of 0 degrees C and withdrawal latencies were measured. Additionally, incision-induced cold hyperalgesia was also assessed in female animals. Furthermore, skin temperature before and after plantar incision and inflammation were assessed by using infrared thermography (Varioscan LW 3011; Infratec, Dresden, Germany).
Cold hyperalgesia to a noxious cold stimulus was observed after inflammation and nerve injury but not after a surgical incision. Similar results were demonstrated for female animals after incision. Furthermore, a significant increase in skin temperature was recorded after inflammation but not after incision, indicating that a surgery evokes only minor inflammatory effects.
The present data give strong evidence that a surgical incision does not cause cold hyperalgesia. Furthermore, a lack of cold hyperalgesia in unrestrained male and female mice after incision was not due to increased skin temperature after incision. Finally, we demonstrated that in contrast to a surgical incision, inflammation and nerve injury generate intense cold hyperalgesia and an increase in skin temperature, suggesting that different mechanisms are involved in surgical and inflammatory or neuropathic pain.
Anesthesia and analgesia 11/2009; 110(1):222-7. · 3.08 Impact Factor
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ABSTRACT: Peripheral nerve injury may lead to the formation of a painful neuroma. In patients, palpating the tissue overlying a neuroma evokes paraesthesias/dysaesthesias in the distribution of the injured nerve. Previous animal models of neuropathic pain have focused on the mechanical hyperalgesia and allodynia that develops at a location distant from the site of injury and not on the pain from direct stimulation of the neuroma. We describe a new animal model of neuroma pain in which the neuroma was located in a position that is accessible to mechanical testing and outside of the innervation territory of the injured nerve. This allowed testing of pain in response to mechanical stimulation of the neuroma (which we call neuroma tenderness) independent of pain due to mechanical hyperalgesia. In the tibial neuroma transposition (TNT) model, the posterior tibial nerve was ligated and transected in the foot just proximal to the plantar bifurcation. Using a subcutaneous tunnel, the end of the ligated nerve was positioned just superior to the lateral malleolus. Mechanical stimulation of the neuroma produced a profound withdrawal behavior that could be distinguished from the hyperalgesia that developed on the hind paw. The neuroma tenderness (but not the hyperalgesia) was reversed by local lidocaine injection and by proximal transection of the tibial nerve. Afferents originating from the neuroma exhibited spontaneous activity and responses to mechanical stimulation of the neuroma. The TNT model provides a useful tool to investigate the differential mechanisms underlying the neuroma tenderness and mechanical hyperalgesia associated with neuropathic pain.
Pain 03/2008; 134(3):320-34. · 5.78 Impact Factor
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ABSTRACT: Activation of A1 adenosine receptors (A1Rs) causes antinociception after nerve injury and inflammation. However, the role of A2a adenosine receptors (A2aRs) for pain processing is less clear. In the current study, the authors investigated the role of spinal adenosine A1Rs and A2aRs for the maintenance of mechanical hyperalgesia in an animal model for postoperative pain.
Rats with intrathecal catheters were anesthetized and underwent plantar incision. Spontaneous pain behavior and withdrawal threshold to punctuate stimulation were measured before and after administration of intrathecal R-phenylisopropyl-adenosine (R-PIA; A1R agonist), 2-w p-2-carbonyl-ethyl-phenylethylaminox-5X-N-ethylcarboxami-doadenosine (CGS21680; A2aR agonist), or vehicle. In separate groups of animals, the effects of pertussis toxin, forskolin, glibenclamide, 4-aminopyridine, tetraethylammonium, apamin, charybdotoxin, or margatoxin on R-PIA-induced antinociception were examined.
Intrathecal administration of 5 nmol R-PIA but not 10 nmol CGS21680 decreased nonevoked spontaneous pain behavior. Furthermore, intrathecal administration of R-PIA but not of CGS21680 increased withdrawal thresholds after incision. Pretreatment with pertussis toxin and administration of forskolin, glibenclamide, 4-aminopyridine, and tetraethylammonium inhibited R-PIA-induced antinociception. In addition, intrathecal administration of apamin, charybdotoxin, or margatoxin did not modify mechanical hypoalgesia mediated by R-PIA.
Spinal A1Rs but not A2aRs play an important role in the maintenance of nonevoked and evoked pain behaviors after an incision. Furthermore, A1R-induced spinal antinociception is mediated by interactions with pertussis toxin-sensitive G proteins. In addition, the opening of adenosine triphosphate-sensitive K channels but not of calcium-activated potassium channels and voltage-gated Kv1.3 or Kv1.6 channels contribute to the antinociceptive effect of A1R agonists.
Anesthesiology 12/2007; 107(5):797-806. · 5.36 Impact Factor
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ABSTRACT: Postoperative incisional pain is a unique and common form of acute pain. Although ample evidence indicates that an efficeous postoperative pain treatment reduces patient morbidity and patient outcome, recent studies demonstrate that about 50-70% of patients experience moderate to severe pain after surgery indicating that postoperative pain remains poorly treated. Perhaps important reasons for this quandary are distinct mechanisms of incisional nociception compared to other pain conditions limiting our regimen to drugs designed for other clinical pain problems. Another reason might be the lack of an in depth knowledge about the pathophysiology and neuropharmacology of postoperative pain. Basic research offers important insights in the mechanisms of postsurgical incisional pain and the translation of experimental results into clinical practice will have important implications on the improvement of new multimodal treatment regimens based postoperative pain mechanisms. In the present review, recent developments in experimental postsurgical incisional pain research will be described and their possible relevance for clinical practice discussed.
Baillière' s Best Practice and Research in Clinical Anaesthesiology 04/2007; 21(1):3-13.
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ABSTRACT: Neuroaxial anesthesia has become an integral part of perioperative pain therapy and provides several advantages over systemic opioids. Despite these benefits, rare but serious complications occur with epidural analgesia including epidural haematoma, spinal-epidural infections and local anesthetic cardiac toxicity. Epidural haematoma and epidural abscess after catheter placement may cause irreversible neurological complications and an immediate diagnostic and therapeutic approach is crucial to assure complete recovery. Furthermore, local anesthetic-induced cardiac toxicity is another rare but potentially lethal complication during regional anesthesia. Based on lipophilic and hydrophilic properties, local anesthetics can interfere with ion channels such as sodium, potassium and calcium channels of the CNS and the heart leading to severe neuronal and cardiac (arrhythmia and contractile depression) adverse effects. In this review we take an in-depth look at severe complications associated with regional anesthesia, describe their symptoms and discuss appropriate diagnostic and therapeutical approaches.
ains · Anästhesiologie · Intensivmedizin 02/2007; 42(1):42-52. · 0.41 Impact Factor
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ABSTRACT: Postoperative pain is now a critical focus of perioperative patient care. The current perioperative analgesic strategy is a "balanced-multimodal analgesia". Cornerstones of this treatment approach are patient controlled neuraxial administration of local anesthetics and opioids or patient controlled intravenous administration of opioids. However, systemic opioids are limited by side effects. Thus, adjuvants like anticonvulsants, NMDA receptor antagonists, alpha-2 adrenergic agonists and other non-Opioid analgesics are considered to reduce pain and opioid requirements in the perioperative period. In the present review we discuss recent findings about the effectiveness of different systemic administered adjuvants including ketamine, lidocaine, gabapentin, pregabalin and corticosteroids for postoperative pain treatment. Furthermore a nurse based oral analgesic concept using controlled released Oxycodon for all postoperative patients without a patient controlled analgesia device will be introduced.
ains · Anästhesiologie · Intensivmedizin 02/2007; 42(1):22-31. · 0.41 Impact Factor
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ABSTRACT: Much effort has been taken to prove that a treatment initiated before surgery is more effective in reducing postoperative pain compared with the same intervention started after surgery. Clinical studies failed to demonstrate major clinical benefits of preemptive analgesia, however, and the results of recent systemic reviews are equivocal. The present review will discuss recent clinical as well as experimental evidence of preemptive analgesia and examine the implications of a preventive postoperative pain treatment.
Recent preclinical and clinical studies give strong evidence that neuronal hypersensitivity and nociception after incision is mainly maintained by the afferent barrage of sensitized nociceptors across the perioperative period. This is in contrast to pain states of other origin in which prolonged hypersensitivity is initiated during the injury. Therefore, not timing but duration and efficacy of an analgesic and antihyperalgesic intervention are most important for treating pain and hyperalgesia after surgery.
Extending a multimodal analgesic treatment into the postoperative period to prevent postoperative pain may be superior compared with preemptive analgesia. In the future, appropriate drug combinations, drug concentrations and duration of preventive strategies need to be determined to be most beneficial for the management of acute and chronic pain after surgery.
Current Opinion in Anaesthesiology 11/2006; 19(5):551-5. · 2.21 Impact Factor
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ABSTRACT: Non-N-methyl-D-aspartate (non-NMDA) glutamate receptor antagonists modify multiple pain transmission pathways and are of particular interest in analgesic development because of their capacity to interfere with evoked pain. Evoked pain is a problem for postoperative patients and is characteristic of the plantar incision model for postoperative pain. The purpose of this study was to assess the efficacy of a non-NMDA receptor antagonist LY293558 on mechanical hyperalgesia after plantar incision in the rat. Parenteral, intrathecal, or intraplantar administration of LY293558 was tested against the mechanical hyperalgesia that characterizes the model. Sprague-Dawley rats were assigned to 1 of 3 groups. LY293558 or vehicle was administered intraperitoneally, intrathecally, or intraplantarly. The hind paw withdrawal threshold to punctate stimulation by using von Frey filaments and response frequency to a nonpunctate stimulus directly to the wound were measured. Motor tests after administration of LY293558 were also examined in rats that did not undergo incision. The greatest dose of parenterally administered LY293558 (34 micromol/kg) decreased the responses to mechanical stimuli after plantar incision. Rotorod performance was decreased at these same times. Intrathecal injection of LY293558 (0.5 and 2.0 nmol) produced inhibition of mechanical sensitivity and produced lower extremity motor side effects. Repeated intrathecal administration produced sustained anesthesia for 24 hours but had no analgesic effect the next day. Local administration did not decrease response after incision. LY293558 was most effective for evoked pain when administered intrathecally. PERSPECTIVE: Control of evoked pain after surgery is inadequate but is linked to perioperative outcome. These data suggest that non-NMDA receptor antagonists like LY293558 will be most effective for evoked pain in postoperative patients if administered spinally.
Journal of Pain 11/2006; 7(10):768-77. · 4.93 Impact Factor
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ABSTRACT: Postoperative pain significantly impacts patient recovery. However, postoperative pain management remains suboptimal, perhaps because treatment strategies are based mainly on studies using inflammatory pain models. We used a recently developed mouse model of incisional pain to investigate peripheral and spinal mechanisms contributing to heat hyperalgesia after incision. Behavioral experiments involving TRPV1 KO mice demonstrate that, as previously observed in inflammatory models, TRPV1 is necessary for heat (but not mechanical) hyperalgesia after incision. However, in WT mice, neither the proportion of TRPV1 immunoreactive neurons in the DRG nor the intensity of TRPV1 staining in the sciatic nerve was different from that in controls up to 4 days after incision. This result was corroborated by immunoblot analysis of sciatic nerve in rats subjected to an incision, and is distinct from that following inflammation of the rat hind paw, a situation in which TRPV1 expression levels in sciatic nerve increases. In the absence of heat exposure, spinal c-Fos staining was similar between incised TRPV1 KO and WT mice. However, differences in c-Fos staining between heat exposed TRPV1 KO and WT mice after incision suggest that the incision-mediated enhancement of heat-evoked signaling to the spinal cord involves a TRPV1-dependent mechanism. Finally, heat hyperalgesia after incision was reversed by antagonism of spinal non-NMDA receptors, unlike inflammatory hyperalgesia, which is mediated via NMDA receptors . Thus, TRPV1 is important for the generation of thermal hyperalgesia after incision. Our observations suggest that all experimental pain models may not be equally appropriate to guide the development of postoperative pain therapies.
Pain 07/2005; 115(3):296-307. · 5.78 Impact Factor
