Peripheral bee venom's anti-inflammatory effect involves activation of the coeruleospinal pathway and sympathetic preganglionic neurons

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 (α2-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.