title: Chemical stimulation of the ST36 acupoint reduces both formalin-induced nociceptive behaviors and spinal astrocyte activation via spinal alpha-2 adrenoceptors.
abstract: Spinal astrocytes have emerged as important mechanistic contributors to pathological and chronic pain. Recently, we have demonstrated that injection of diluted bee venom (DBV) into the Zusanli (ST36) acupoint produces a potent anti-nociceptive effect via the activation of spinal alpha-2 adrenoceptors. However, it is unclear if this anti-nociceptive effect is associated with alterations in spinal astrocytes. Thus, the present study was designed to determine: (1) whether DBV's anti-nociceptive effect in the formalin test involves suppression of spinal astrocyte activation; (2) whether DBV-induced astrocyte inhibition is mediated by spinal alpha-2 adrenoceptors; and (3) whether this glial modulation is potentiated by intrathecal administration of the glial metabolic inhibitor, fluorocitrate (FC) in combination with DBV injection. DBV was injected directly into the ST36 acupoint, and spinal expression of the astrocytic marker, glial fibrillary acidic protein (GFAP), was assessed together with effects on formalin-induced nociception. DBV treatment reduced pain responses in the late phase of the formalin test and significantly blocked the formalin-evoked increase in spinal GFAP expression. These effects of DBV were prevented by intrathecal pretreatment with selective alpha-2A and alpha-2C adrenoceptor antagonists. Moreover, low dose intrathecal injection of FC in conjunction with low dose DBV injection into the ST36 acupoint synergistically suppressed pain responses and GFAP expression. These results demonstrate that DBV stimulation of the ST36 acupoint inhibits the formalin-induced activation of spinal astrocytes and nociceptive behaviors in this inflammatory pain model and this inhibition is associated with the activation of spinal alpha-2 adrenoceptors.
authors: Department of Veterinary Physiology, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 151-742, Republic of Korea.
authors: Suk-Yun
authors: SY
authors: Kang
authors: Chi-Young
authors: CY
authors: Kim
authors: Dae-Hyun
authors: DH
authors: Roh
authors: Seo-Yeon
authors: SY
authors: Yoon
authors: Ji-Ho
authors: JH
authors: Park
authors: Hye-Jung
authors: HJ
authors: Lee
authors: Alvin J
authors: AJ
authors: Beitz
authors: Jang-Hern
authors: JH
authors: Lee
mesh_terms: D015669:Acupuncture Points; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001514:Bee Venoms / Q000008:administration & dosage / Q000494:pharmacology; D002951:Citrates / Q000008:administration & dosage / Q000494:pharmacology; D005557:Formaldehyde / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D019329:Idazoxan / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007278:Injections, Spinal; D054833:Isoindoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010146:Pain / Q000139:chemically induced* / Q000188:drug therapy; D059408:Pain Management / Q000379:methods; D010147:Pain Measurement / Q000379:methods; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology*; D013268:Stimulation, Chemical
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D000700:Analgesics; D001514:Bee Venoms; D002951:Citrates; D005904:Glial Fibrillary Acidic Protein; D007093:Imidazoles; D054833:Isoindoles; D018341:Receptors, Adrenergic, alpha-2; D005557:Formaldehyde; C007744:fluorocitrate; D019329:Idazoxan; C072125:BRL 44408