Electroacupuncture-induced analgesia in a rat model of ankle sprain pain is mediated by spinal α-adrenoceptors

Department of Medical Research, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea.
Pain (Impact Factor: 5.21). 04/2008; 135(1-2):11-9. DOI: 10.1016/j.pain.2007.04.034
Source: PubMed


In a previous study, we showed that electroacupuncture (EA) applied to the SI-6 point on the contralateral forelimb produces long-lasting and powerful analgesia in pain caused by ankle sprain in a rat model. To investigate the underlying mechanism of EA analgesia, the present study tested the effects of various antagonists on known endogenous analgesic systems in this model. Ankle sprain was induced in anesthetized rats by overextending their right ankle with repeated forceful plantar flexion and inversion of the foot. When rats developed pain behaviors (a reduction in weight-bearing of the affected hind limb), EA was applied to the SI-6 point on the contralateral forelimb for 30 min under halothane anesthesia. EA significantly improved the weight-bearing capacity of the affected hind limb for 2h, suggesting an analgesic effect. The alpha-adrenoceptor antagonist phentolamine (2mg/kg, i.p. or 30 microg, i.t.) completely blocked the EA-induced analgesia, whereas naloxone (1mg/kg, i.p.) failed to block the effect. These results suggest that EA-induced analgesia is mediated by alpha-adrenoceptor mechanisms. Further experiments showed that intrathecal administration of yohimbine, an alpha(2)-adrenergic antagonist, reduced the EA-induced analgesia in a dose-dependent manner, whereas terazosin, an alpha(1)-adrenergic antagonist, did not produce any effect. These data suggest that the analgesic effect of EA in ankle sprain pain is, at least in part, mediated by spinal alpha(2)-adrenoceptor mechanisms.

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    • "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; 2008) and based on our results mice could also be used to successfully induce and follow after an ankle sprain. "
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    ABSTRACT: 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.
    Full-text · Article · Sep 2015 · Journal of sports science & medicine
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    • "In recent years, it has received attention as an alternative method of medicine in Western countries [36, 37]. For decades ago, it has been demonstrated in many clinical and animal studies that acupuncture or EA analgesia is mediated by the endogenous analgesic systems, especially opioid [13, 16, 18, 38] and noradrenergic inhibitory systems [14, 15, 17, 39, 40]. Our previous studies using a rat model of peripheral nerve injury suggested that both of the opioid and noradrenergic systems equally contributed to the anti-allodynic effects of EA [41–43]. "
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    ABSTRACT: Oxaliplatin, a chemotherapy drug, often leads to neuropathic cold allodynia after a single administration. Bee venom acupuncture (BVA) has been used in Korea to relieve various pain symptoms and is shown to have a potent antiallodynic effect in nerve-injured rats. We examined whether BVA relieves oxaliplatin-induced cold allodynia and which endogenous analgesic system is implicated. The cold allodynia induced by an oxaliplatin injection (6 mg/kg, i.p.) was evaluated by immersing the rat's tail into cold water (4°C) and measuring the withdrawal latency. BVA (1.0 mg/kg, s.c.) at Yaoyangguan (GV3), Quchi (LI11), or Zusanli (ST36) acupoints significantly reduced cold allodynia with the longest effect being shown in the GV3 group. Conversely, a high dose of BVA (2.5 mg/kg) at GV3 did not show a significant antiallodynic effect. Phentolamine ( α -adrenergic antagonist, 2 mg/kg, i.p.) partially blocked the relieving effect of BVA on allodynia, whereas naloxone (opioid antagonist, 2 mg/kg, i.p.) did not. We further confirmed that an intrathecal administration of idazoxan ( α 2-adrenergic antagonist, 50 μ g) blocked the BVA-induced anti-allodynic effect. These results indicate that BVA alleviates oxaliplatin-induced cold allodynia in rats, at least partly, through activation of the noradrenergic system. Thus, BVA might be a potential therapeutic option in oxaliplatin-induced neuropathy.
    Full-text · Article · Aug 2013 · Evidence-based Complementary and Alternative Medicine
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    • "In 2009, approximately 2.8 million Korean people were diagnosed with an ankle injury, making ankle injury the fifth most common reason for visits to Korean Medicine clinics, and of them 1.2 million sought acupuncture treatment [12]. Clinical experience and some animal studies indicate that ankle sprain responds rapidly to acupuncture, which alleviates the intensity and duration of pain, contributing to a prompt return to pre-injury activity [13,14]. Given its popular use and claimed effectiveness, however, the evidence in support of acupuncture for treating ankle sprain remains unclear. "
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    ABSTRACT: Background Ankle sprain is one of the most frequently encountered musculoskeletal injuries; however, the efficacy of acupuncture in treating ankle sprains remains uncertain. We therefore performed a systematic review to evaluate the evidence regarding acupuncture for ankle sprains. Methods We searched 15 data sources and two trial registries up to February 2012. Randomized controlled trials of acupuncture were included if they involved patients with ankle sprains and reported outcomes of symptom improvement, including pain. A Cochrane risk of bias assessment tool was used. Risk ratio (RR) or mean difference (MD) was calculated with 95% confidence intervals (CIs) in a random effects model. Subgroup analyses were performed based on acupuncture type, grade of sprain, and control type. Sensitivity analyses were also performed with respect to risk of bias, sample size, and outcomes reported. Results Seventeen trials involving 1820 participants were included. Trial quality was generally poor, with just three reporting adequate methods of randomization and only one a method of allocation concealment. Significantly more participants in acupuncture groups reported global symptom improvement compared with no acupuncture groups (RR of symptoms persisting with acupuncture = 0.56, 95% CI 0.42–0.77). However, this is probably an overestimate due to the heterogeneity (I2 = 51%) and high risk of bias of the included studies. Acupuncture as an add-on treatment also improved global symptoms compared with other treatments only, without significant variability (RR 0.61, 95% CI 0.51–0.73, I2 = 1%). The benefit of acupuncture remained significant when the analysis was limited to two studies with a low risk of bias. Acupuncture was more effective than various controls in relieving pain, facilitating return to normal activity, and promoting quality of life, but these analyses were based on only a small number of studies. Acupuncture did not appear to be associated with adverse events. Conclusions Given methodological shortcomings and the small number of high-quality primary studies, the available evidence is insufficient to recommend acupuncture as an evidence-based treatment option. This calls for further rigorous investigations.
    Full-text · Article · Mar 2013 · BMC Complementary and Alternative Medicine
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