title: 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.
abstract: Although intrathecal (i.t.) administration of the alpha(2)-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 alpha(2)-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine and BK21 Program for Veterinary Science, Seoul National University, Seoul, South Korea.
authors.forename: Seo-Yeon
authors.initials: SY
authors.lastname: Yoon
authors.forename: Dae-Hyun
authors.initials: DH
authors.lastname: Roh
authors.forename: Young-Bae
authors.initials: YB
authors.lastname: Kwon
authors.forename: Hyun-Woo
authors.initials: HW
authors.lastname: Kim
authors.forename: Hyoung-Sig
authors.initials: HS
authors.lastname: Seo
authors.forename: Ho-Jae
authors.initials: HJ
authors.lastname: Han
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: D015669:Acupuncture Points; D000700:Analgesics / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D001514:Bee Venoms / Q000008:administration & dosage / Q000627:therapeutic use*; D003000:Clonidine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy*; D007278:Injections, Spinal; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000700:Analgesics; D001514:Bee Venoms; D003000:Clonidine