Acupoint Stimulation With Diluted Bee Venom (Apipuncture) Potentiates the Analgesic Effect of Intrathecal Clonidine in the Rodent Formalin Test and in a Neuropathic Pain Model

Seo Yeon Yoon, Dae Hyun Roh, Young Bae Kwon, Hyun Woo Kim, Hyoung Sig Seo, Ho Jae Han, Hye Jung Lee, Alvin J. Beitz, Jang Hern Lee

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39 Scopus citations


Although intrathecal (i.t.) administration of the α2-adrenoceptor agonist clonidine has a pronounced analgesic effect, the clinical use of clonidine is limited by its side effects. Previously, our laboratory has demonstrated that the subcutaneous injection of diluted bee venom (DBV) into an acupoint (termed apipuncture) produces significant analgesic effect in various pain animal models. The present study was designed to examine whether DBV injection into the Zusanli acupoint (ST-36) could enhance lower-dose clonidine-induced analgesic effects without the development of hypotension, bradycardia, or sedation. In the mouse formalin test, DBV injection produced a dramatic leftward shift in the dose-response curve for clonidine-induced analgesia. In a rat neuropathic pain model i.t. clonidine dose dependently suppressed chronic constriction injury (CCI)-induced mechanical allodynia and thermal hyperalgesia, and this clonidine-induced analgesic effect was significantly potentiated by apipuncture pretreatment. DBV apipuncture alone or in combination with a low dose of i.t. clonidine produced an analgesic effect similar to that of the high dose of clonidine, but without significant side effects. The analgesic effect produced by the combination of i.t. clonidine and apipuncture was completely blocked by pretreatment with an α2-adrenoceptor antagonist. These data show that DBV-apipuncture significantly enhances clonidine-induced analgesia and suggest that a combination of low dose clonidine with acupuncture therapy represents a novel strategy for pain management that could eliminates clonidine's side effects. Perspective: This study demonstrated that intrathecal clonidine-induced analgesia is significantly enhanced when it is combined with chemical acupuncture treatment. The administration of low-dose clonidine in combination with acupuncture produced a potent analgesic effect without significant side effects and thus represents a potential novel strategy for the management of chronic pain.

Original languageEnglish (US)
Pages (from-to)253-263
Number of pages11
JournalJournal of Pain
Issue number3
StatePublished - Mar 2009

Bibliographical note

Funding Information:
Supported by a grant (M103KV010015-08K2201-01510) from Brain Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, the Republic of Korea. This work was also supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) (R11-2005-014).


  • Clonidine
  • diluted bee venom
  • formalin test
  • neuropathic pain
  • α-adrenoceptor


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