Analgesic Effects of Diluted Bee Venom Acupuncture Mediated by δ-Opioid and α2-Adrenergic Receptors in Osteoarthritic Rats.

Context • Pain from osteoarthritis is associated with peripheral nociception and central pain processing. Given the unmet need for innovative, effective, and well-tolerated therapies, many patients, after looking for more satisfactory alternatives, decide to use complementary and alternative modalities. The analgesic mechanism of subcutaneous injections of diluted bee venom into an acupoint is thought to be part of an anti-inflammatory effect and the central modulation of pain processing. Objectives • Using the rat model of collagenase-induced osteoarthritis (CIOA), the study intended to investigate the analgesic effects of bee venom acupuncture (BVA) as they are related to the acupuncture points and dosage used and to determine whether the analgesic mechanisms of BVA for pain were mediated by opioid or adrenergic receptors. Design • Male Sprague-Dawley rats were randomly assigned to one of 19 groups, with n = 10 for each group. Setting • The study was conducted at the East-West Bone and Joint Research Institute at Kyung Hee University (Seoul, South Korea). Intervention • All rats were intra-articularly injected with collagenase solution in the left knee, followed by a booster injection performed 4 d after the first injection. For the groups receiving BVA treatments, the treatment was administered into the ST-36 acupoint, except for 1 group that received the treatment into a nonacupoint. Three BVA intervention groups received no pretreatment with agonists or antagonists; 1 of them received a dose of 1 mg/kg of bee venom into acupoint ST-36, 1 received a dose of 2 mg/kg into acupoint ST-36, and 1 received a dose of 1 mg/kg into a nonacupoint location. For the intervention groups receiving pretreatments, the opioid-receptor or adrenergic-receptor agonists or antagonists were injected 20 min before the 1-mg/kg BVA treatments. Outcome Measures • Changes in the rats' pain thresholds were assessed by evaluation of pain-related behavior, using a tail flick latency unit. Results • The pain reached its maximum value after 4 wk of CIOA induction. The 1-mg/kg ST-36 BVA treatment resulted in a more significant analgesic effect than nonacupoint BVA. Pain-related behavior was more effectively improved by treatment with 1 mg/kg of BVA than with 2 mg/kg of BVA. The analgesic effects of the BVA were not synergistic with the agonist pretreatments with the μ-, δ-, or κ-opioid receptors or with the α1-, α2-, and β-adrenergic receptors. The analgesic effects of the BVA were not decreased by the antagonist pretreatments for the μ- or κ-opioid receptors or for the α1- or β-adrenergic receptors. The ST-36-BVA-induced analgesia was inhibited by the antagonist pretreatments for the δ-opioid receptor and the α2-adrenergic receptor. Conclusion • The ST-36 BVA treatment exerted an analgesic effect on CIOA-induced pain through the partial involvement of the δ-opioid and α2-adrenergic receptors.