Abstract

Cold allodynia is an important distinctive feature of neuropathic pain. The present study examined whether single or repetitive treatment of diluted bee venom (DBV) reduced cold allodynia in sciatic nerve chronic constriction injury (CCI) rats and whether these effects were mediated by spinal adrenergic receptors. Single injection of DBV (0.25 or 2.5 mg/kg) was performed into Zusanli acupoint 2 weeks post CCI, and repetitive DBV (0.25 mg/kg) was injected for 2 weeks beginning on day 15 after CCI surgery. Single treatment of DBV at a low dose (0.25 mg/kg) did not produce any anticold allodynic effect, while a high dose of DBV (2.5 mg/kg) significantly reduced cold allodynia. Moreover, this effect of high-dose DBV was completely blocked by intrathecal pretreatment of idazoxan (α2-adrenoceptor antagonist), but not prazosin (α1-adrenoceptor antagonist) or propranolol (nonselective β-adrenoceptor antagonist). In addition, coadministration of low-dose DBV (0.25 mg/kg) and intrathecal clonidine (α2-adrenoceptor agonist) synergically reduced cold allodynia. On the other hand, repetitive treatments of low-dose DBV showing no motor deficit remarkably suppressed cold allodynia from 7 days after DBV treatment. This effect was also reversed by intrathecal idazoxan injection. These findings demonstrated that single or repetitive stimulation of DBV could alleviate CCI-induced cold allodynia via activation of spinal α2-adrenoceptor.

Highlights

  • IntroductionNeuropathic pain, which is related to the development of hyperalgesia (an increased response to a stimulus that is normally painful) and allodynia (pain as a result of a stimulus that does not provoke pain), is one of several forms of chronic pain in humans and animals [1]

  • Neuropathic pain, which is related to the development of hyperalgesia and allodynia, is one of several forms of chronic pain in humans and animals [1]

  • The results from the present study show that the repetitive diluted bee venom (DBV) treatment in constriction injury (CCI) animals (R-DBV: 0.25 mg) had no effect on duration of time spent on the rotarod after daily treatments compared with the repetitive saline-treated CCI rats (R-Saline, Table 2)

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Summary

Introduction

Neuropathic pain, which is related to the development of hyperalgesia (an increased response to a stimulus that is normally painful) and allodynia (pain as a result of a stimulus that does not provoke pain), is one of several forms of chronic pain in humans and animals [1]. Numerous studies on neuropathic pain treatment have attempted to elucidate pathophysiological mechanisms in humans and experimental animals, the presence of several side effects, such as motor dysfunction, sedation, dependence, and tolerance, have limited their application for the treatment of this chronic pain condition [2, 3]. Despite the importance of cold allodynia in neuropathic pain patients, the distinct effects of various treatments are still unclear. Previous experimental studies in our laboratory provide support for this alternative medicine approach by demonstrating that a prominent antinociceptive and antihyperalgesic effect is produced by apipuncture in several animal models of pain including the formalin test, the writhing test, the carrageenan-induced inflammatory pain test, and models of arthritis [9,10,11,12]

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