Acupoint stimulation with diluted bee venom (apipuncture) alleviates thermal hyperalgesia in a rodent neuropathic pain model: Involvement of spinal alpha2-adrenoceptors

Dae Hyun Roh, Young Bae Kwon, Hyun Woo Kim, Tae Won Ham, Seo Yeon Yoon, Seuk Yun Kang, Ho Jae Han, Hye Jung Lee, Alvin J. Beitz, Jang Hern Lee

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70 Scopus citations


Chemical acupuncture with diluted bee venom (DBV), termed apipuncture, has been traditionally used in oriental medicine to treat several inflammatory diseases and chronic pain conditions. In the present study we investigated the potential antihyperalgesic and antiallodynic effects of apipuncture in a rat neuropathic pain model. DBV (0.25 mg/kg, subcutaneous) was injected into the Zusanli acupoint 2 weeks after chronic constrictive injury (CCI) of the sciatic nerve. Between 5 and 45 minutes after DBV injection, we observed a significant reduction in the thermal hyperalgesia induced by CCI, but apipuncture failed to reduce CCI-induced mechanical allodynia. We subsequently examined whether this antihyperalgesic effect of apipuncture was related to the activation of spinal opioid receptors and/or alpha2-adrenoceptors. Intrathecal pretreatment with naloxone (10 μg/rat), an opioid receptor antagonist, did not reverse the antihyperalgesic effect of apipuncture, whereas pretreatment with idazoxan (40 μg/rat), an alpha2-adrenoceptor antagonist, completely blocked the effect of apipuncture. These results indicate that DBV-induced apipuncture significantly reduces the thermal hyperalgesia generated by CCI and also suggest that this antihyperalgesic effect is dependent on the activation of alpha2-adrenoceptors, but not opioid receptors, in the spinal cord. Perspective The antinociceptive effect of apipuncture was evaluated in a rodent neuropathic pain model. The relieving effect of apipuncture on thermal hyperalgesia was found to be mediated by spinal alpha 2-adrenoceptors, but not opioid receptors. These data suggest that apipuncture might be an effective alternative therapy for patients with painful peripheral neuropathy, especially for those who are poorly responsive to opioid analgesics.

Original languageEnglish (US)
Pages (from-to)297-303
Number of pages7
JournalJournal of Pain
Issue number6
StatePublished - Aug 2004

Bibliographical note

Funding Information:
Supported by a grant (M103KV010009 03K2201 00940) from the Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology of the Republic of Korea. The publication of this manuscript was also supported by a Research Fund from the Research Institute for Veterinary Science (RIVS) in the College of Veterinary Medicine, Seoul National University, as well as funds from the Brain Korea 21 project.


  • Neuropathic pain
  • acupuncture
  • alpha 2-adrenoceptor
  • bee venom
  • hyperalgesia


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