The Role Of The Peripheral Acid-sensing Ion Channels In Bee Venom-induced Spontaneous Pain, Hyperalgesia, And Inflammation In Rats

ObjectiveTo observe the effects of intraplantar injection of amiloride, an inhibitor of the acid-sensing ion channels (ASIC), on bee venom-induced spontaneous pain, hyperalgesia, and inflammatory response, and investigate the role of ASIC in the underlying mechanism of inflammatory pain.Methods100male SD adult rats were randomly divided into ten groups (n=10/group). The drug or vehicle was intraplantarly administrated following measuring rat paw withdrawal mechanical threshold (PWMT) and paw volume (PV). Twenty minutes later, bee venom (0.2mg/50ul) was intraplantarly injected into left hind paw, and spontaneous flinching reflexes were observed for1hour. Two hour later, PWMT and PV were measured again. In capsaicin group, the sciatic nerve was exposed in one of the hind limbs, and a piece of cotton soaked with0.15%capsaicin solution or vehicle was gently wrapped around1cm of the target nerve for30min.1day later, The drug or vehicle was intraplantarly administrated following measuring PWMT and PV. Twenty minutes later, bee venom (0.2mg/50ul) was intraplantarly injected into left hind paw, and spontaneous flinching reflexes were observed for1hour. Two hour later, PWMT and PV were measured again.Results1. Intraplantar injection of bee venom into one hind paw in rats can induce persistent spontaneous flinching reflexes (PSFR) lasting for1hour, decrease in PWMT and increase in PV of the injected paw.2. Compared with control group, pretreatment with Intraplantar injection of amiloride produced a significant inhibition of bee venom-induced PSFR and decrease in PWMT in a dose-related manner, but had no effect on bee venom-induced paw edema. Intraplantar injection of amiloride into contralateral hind paw had no effect on bee venom-induced PSFR and decrease in PWMT, ruling out the systemic effect.3. Compared with capsaicin group, amiloride adminstration following capsaicin treatment had no further inhibitory effect on bee venom-induced PSFR.Conclusions1.The peripheral acid-sensing ion channels activation may contribute to bee venom-induced spontaneous pain and mechanical hyperalgesia, but not inflammatory response.2. The peripheral acid-sensing ion channels located in capsaicin sensitive primary afferent fibers participate in the development of bee venom-induced inflammatory pain.