Bee Venom Injection Significantly Reduces Nociceptive Behavior in the Mouse Formalin Test via Capsaicin-Insensitive Afferents

Dae Hyun Roh, Hyun Woo Kim, Seo Yeon Yoon, Seuk Yun Kang, Young Bae Kwon, Kwang Hyun Cho, Ho Jae Han, Yeon Hee Ryu, Sun Mi Choi, Hye Jung Lee, Alvin J. Beitz, Jang Hern Lee

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


Peripheral bee venom (BV) administration produces 2 contrasting effects, nociception and antinociception. This study was designed to evaluate whether the initial nociceptive effect induced by BV injection into the Zusanli acupoint is involved in producing the more prolonged antinociceptive effect observed in the mouse formalin test, and whether capsaicin-sensitive primary afferents are involved in these effects. BV injection into the Zusanli point increased spinal Fos expression but not spontaneous nociceptive behavior. BV pretreatment 10 minutes before intraplantar formalin injection dose-dependently attenuated nociceptive behavior associated with the second phase of the formalin test. The destruction of capsaicin-sensitive primary afferents by resiniferatoxin (RTX) pretreatment selectively decreased BV-induced spinal Fos expression but did not affect BV-induced antinociception. Furthermore, BV injection increased Fos expression in tyrosine hydroxylase immunoreactive neurons in the locus caeruleus, and this expression was unaltered by RTX pretreatment. Finally, BV's antinociception was blocked by intrathecal injection of 10 μg idazoxan, and this effect was not modified by RTX pretreatment. These findings suggest that subcutaneous BV stimulation of the Zusanli point activates central catecholaminergic neurons via capsaicin-insensitive afferent fibers without induction of nociceptive behavior. This in turn leads to the activation of spinal α2-adrenoceptors, which ultimately reduces formalin-evoked nociceptive behaviors. Perspective: This study demonstrates that BV acupuncture produces a significant antinociception without nociceptive behavior in rodents, which is mediated by capsaicin-insensitive afferents and involves activation of central adrenergic circuits. These results further suggest that BV stimulation into this acupuncture point might be a valuable alternative to traditional electrical or mechanical acupoint stimulation.

Original languageEnglish (US)
Pages (from-to)500-512
Number of pages13
JournalJournal of Pain
Issue number7
StatePublished - Jul 2006

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 and by SRC program of KOSEF (R11-2005-014) as well as the Brain Korea 21 project.


  • Bee venom
  • capsaicin-sensitive primary afferents
  • formalin test
  • fos
  • resiniferatoxin


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