title: Peripheral bee venom's anti-inflammatory effect involves activation of the coeruleospinal pathway and sympathetic preganglionic neurons.
abstract: There are several reports indicating that the locus coeruleus (LC) is capable of altering immune responses. Moreover, it is well established that the LC is the major source of descending noradrenergic system. Recently we have demonstrated that subcutaneous bee venom (BV) injection dramatically suppressed peripheral inflammation through activation of sympathetic preganglionic neurons (SPNs) leading to release of adreno-medullary catecholamines. Importantly, this 'BV-induced anti-inflammatory effect' (BVAI) is also associated with an increase of the activity of LC. Based on these data, present study examined whether BV-induced LC activation increased the activity of SPNs and this pathway played a role in BVAI using a zymosan-induced inflammatory air pouch model in mice. Unilateral BV injection into left hind limb produced anti-inflammation and specifically increased Fos expression in SPNs of the T7-T11 (which mainly project to adrenal medulla), but not those of the T1-T6 or T12-L2 spinal cord. 6-Hydroxydopamine-induced unilateral lesion of the contralateral, but not ipsilateral (to the BV injection site) LC significantly blocked BVAI and BV-induced Fos expression in SPNs. Additionally, intrathecal administration of idazoxan (alpha2-adrenoceptor antagonist), blocked BVAI. These results indicate that BV-induced activation of the contralateral LC-descending noradrenergic pathway increased the activity of SPNs that project to the adrenal medulla and this pathway is necessary for BVAI.
authors.affiliation: Biotherapy Human Resources Center, College of Veterinary Medicine, Chonnam National University, Gwang-ju, South Korea.
authors.forename: Seo-Yeon
authors.initials: SY
authors.lastname: Yoon
authors.forename: Young-Bae
authors.initials: YB
authors.lastname: Kwon
authors.forename: Hyun-Woo
authors.initials: HW
authors.lastname: Kim
authors.forename: Dae-Hyun
authors.initials: DH
authors.lastname: Roh
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: Sun-Wook
authors.initials: SW
authors.lastname: Hwang
authors.forename: Jang-Hern
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D001514:Bee Venoms / Q000008:administration & dosage*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007839:Functional Laterality; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D007278:Injections, Spinal / Q000379:methods; D008125:Locus Coeruleus / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology*; D017779:Sympathetic Fibers, Postganglionic / Q000473:pathology*; D013565:Sympatholytics / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001514:Bee Venoms; D016761:Oncogene Proteins v-fos; D013565:Sympatholytics; D016627:Oxidopamine; D002795:Choline O-Acetyltransferase