Substantial role of locus coeruleus-noradrenergic activation and capsaicin-insensitive primary afferent fibers in bee venom's anti-inflammatory effect.
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.
Kwon
Young Bae
YB
Department of Pharmacology, Institute for Medical Science, Chonbuk National University Medical School, Jeonju, South Korea.
Yoon
Seo Yeon
SY
Kim
Hyun Woo
HW
Roh
Dae Hyun
DH
Kang
Seuk Yun
SY
Ryu
Yeon Hee
YH
Choi
Sun Mi
SM
Han
Ho Jae
HJ
Lee
Hye Jung
HJ
Kim
Kee Won
KW
Beitz
Alvin J
AJ
Lee
Jang Hern
JH
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
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