Substantial role of locus coeruleus-noradrenergic activation and capsaicin-insensitive primary afferent fibers in bee venom's anti-inflammatory effect

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

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)197-203
Number of pages7
JournalNeuroscience Research
Volume55
Issue number2
DOIs
StatePublished - Jun 2006

Keywords

  • Bee venom
  • Capsaicin-sensitive primary afferent fibers
  • Fos
  • Inflammation
  • Locus coeruleus

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