title: Bee venom injection significantly reduces nociceptive behavior in the mouse formalin test via capsaicin-insensitive afferents.
abstract: 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 microg 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 alpha2-adrenoceptors, which ultimately reduces formalin-evoked nociceptive behaviors.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine and School of Agricultural Biotechnology, Seoul National University, Seoul, South Korea.
authors.forename: Dae-Hyun
authors.initials: DH
authors.lastname: Roh
authors.forename: Hyun-Woo
authors.initials: HW
authors.lastname: Kim
authors.forename: Seo-Yeon
authors.initials: SY
authors.lastname: Yoon
authors.forename: Seuk-Yun
authors.initials: SY
authors.lastname: Kang
authors.forename: Young-Bae
authors.initials: YB
authors.lastname: Kwon
authors.forename: Kwang-Hyun
authors.initials: KH
authors.lastname: Cho
authors.forename: Ho-Jae
authors.initials: HJ
authors.lastname: Han
authors.forename: Yeon-Hee
authors.initials: YH
authors.lastname: Ryu
authors.forename: Sun-Mi
authors.initials: SM
authors.lastname: Choi
authors.forename: Hye-Jung
authors.initials: HJ
authors.lastname: Lee
authors.forename: Alvin J
authors.initials: AJ
authors.lastname: Beitz
authors.forename: Jang-Hern
authors.initials: JH
authors.lastname: Lee
mesh_terms: D015667:Acupuncture Analgesia / Q000379:methods* / Q000592:standards; D015669:Acupuncture Points; D000344:Afferent Pathways / Q000187:drug effects* / Q000502:physiology; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001514:Bee Venoms / Q000494:pharmacology* / Q000627:therapeutic use; D002211:Capsaicin / Q000494:pharmacology; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology; D004351:Drug Resistance / Q000187:drug effects / Q000502:physiology; D008125:Locus Coeruleus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D009498:Neurotoxins / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000096:biosynthesis; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000700:Analgesics; D001514:Bee Venoms; D004224:Diterpenes; D009498:Neurotoxins; D016760:Proto-Oncogene Proteins c-fos; D018341:Receptors, Adrenergic, alpha-2; C024353:resiniferatoxin; D014446:Tyrosine 3-Monooxygenase; D002211:Capsaicin; D009638:Norepinephrine