title: Substantial role of locus coeruleus-noradrenergic activation and capsaicin-insensitive primary afferent fibers in bee venom's anti-inflammatory effect.
abstract: Several lines of evidence indicate significant interactions between the immune and nervous systems. Our recent study reveals that 'bee venom (BV) induced anti-inflammatory effect' (BVAI) was produced by sympathetic preganglionic neuronal activation and subsequent adrenomedullary catecholamine release in a zymosan-induced inflammation model. However, the specific peripheral input and the supraspinal neuronal systems that are involved in this BVAI remain to be defined. Here we show that subcutaneous BV injection into left hind limb significantly reduces zymosan-induced leukocyte migration and that this effect is completely inhibited by denervation of the left sciatic nerve. This BVAI was not affected by the destruction of capsaicin-sensitive primary afferent fibers using either neonatal capsaicin or resiniferatoxin (RTX) pretreatment. BV injection into the left hind limb significantly increased Fos expression in the contralateral locus coeruleus (LC) in non-inflamed mice. In zymosan-inflamed mice, BV injection produced a further increase in LC Fos expression as compared with non-inflamed mice. This BV-induced Fos increase in the LC was not affected by RTX pretreatment. Pharmacological blockage of central noradrenergic activity by either central chemical sympathectomy (i.c.v. 6-hydroxydopamine) or alpha2 adrenoceptor antagonism (i.c.v. idazoxan) completely blocked BVAI. Taken together, these results suggest that BVAI is mediated by peripheral activation of capsaicin-insensitive primary afferent fibers and subsequent central noradrenergic activation including the LC.
authors.affiliation: Department of Pharmacology, Institute for Medical Science, Chonbuk National University Medical School, Jeonju, South Korea.
authors.forename: Young Bae
authors.initials: YB
authors.lastname: Kwon
authors.forename: Seo Yeon
authors.initials: SY
authors.lastname: Yoon
authors.forename: Hyun Woo
authors.initials: HW
authors.lastname: Kim
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Roh
authors.forename: Seuk Yun
authors.initials: SY
authors.lastname: Kang
authors.forename: Yeon Hee
authors.initials: YH
authors.lastname: Ryu
authors.forename: Sun Mi
authors.initials: SM
authors.lastname: Choi
authors.forename: Ho Jae
authors.initials: HJ
authors.lastname: Han
authors.forename: Hye Jung
authors.initials: HJ
authors.lastname: Lee
authors.forename: Kee Won
authors.initials: KW
authors.lastname: Kim
authors.forename: Alvin J
authors.initials: AJ
authors.lastname: Beitz
authors.forename: Jang Hern
authors.initials: JH
authors.lastname: Lee
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001514:Bee Venoms / Q000627:therapeutic use*; D002211:Capsaicin / Q000494:pharmacology; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology; D004347:Drug Interactions; D007839:Functional Laterality; D015870:Gene Expression / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008125:Locus Coeruleus / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D009638:Norepinephrine / Q000378:metabolism*; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology; D020426:Sciatic Neuropathy / Q000178:diet therapy / Q000473:pathology / Q000503:physiopathology; D015054:Zymosan
chemical_list: D018663:Adrenergic Agents; D000893:Anti-Inflammatory Agents; D001514:Bee Venoms; D004224:Diterpenes; D016761:Oncogene Proteins v-fos; D016627:Oxidopamine; D015054:Zymosan; C024353:resiniferatoxin; D002211:Capsaicin; D009638:Norepinephrine