Role Of Vanilloid Receptor 1 In The Development Of Rats Inflammatory Pain

Objective Vanilloid receptor 1(VR1) is thought to play an important role in inflammatory thermal hyperalgesia,but the underlying mechanisms are not fully explored.Here,the contribution of peripheral VR1 receptor to the nociceptive transduction in rats with unilaterally intraplantar carrageenan-induced inflammation was studied.Methods 1%carrageenan was injected into the plantar region of the right hind paw of rats to produce acute peripheral inflammation;the contralateral was given saline.Animals were transcardially perfused with 0.1 M phosphate-buffer(pH 7.4) under chloral hydrate(300 mg/kg, i.p.) anesthesia.Then,dorsal root ganglia(DRG) neurons at the level of lumbar 4 to lumbar 6 were pooled.As for the plantar skin,after being excised,they were well minced with scissors,and then put into liquid nitrogen.VR1 protein expression were investigated with Western blot. Under chloral hydrate(300 mg/kg,i.p.) anesthesia,the tibineal nerve was exposed,Compound action potentials were extracellularly recorded with bipolar hook electrodes.A period of 30 min was left to allow the preparation to be stable before the intraplantar injection of reagent. Following stabilization,the VR1 receptor sensitivity of the nerve was detected by intraplantaral injection of capsaicin into the receptive field at doses of 1 and 10μg/10μl.The effect of each concentration of capsaicin was monitored for up to 10min.Subsequently,the effect of pretreatment(10 min before i.pl.capsaicin) with intraplantar capsazepine,a competitive VR1 receptor antagonist,into the same receptive field was studied.Results Western blotting analysis revealed that there was no significant difference of the VR1 protein expression in the L4-L6 DRGs and plantar skin between the inflamed and non-inflamed side 6h following carrageenan injection.When the non-inflamed paw was given 1μg of capsaicin,the activity of the tibineal nerve slightly and transiently increased;the increased activity lasted about 20s.By contrast, in the inflamed paw,capsaicin(1μg)-evoked activity lasted about 60 s and the number of peak firing was 2.9 times more than that of the non-inflamed paw.Capsaicin at a higher dose of 10μg produced firing with 4.7-min duration in the non-inflamed paw,and the number of peak firing was similar to that of capsaicin(1μg) action on the carrageenan -treated paw.In the inflamed paw,capsaicin(10μg)-evoked activity lasted 4.5 min,but the number of peak firing was 3.1 times more than that of non-inflamed paw.Capsaicin(1μg)-evoked activity in the inflamed paw was almost completely abolished by local pretreatment with a VR1 receptor antagonist capsazepine(10μg)Conclusion These results suggest that VR1 receptors are involved in the inflammation-induced thermal hyperalgesia,and these results also present the hint that increase in VR1 sensitivity but not VR1 protein expression in the periphery may chiefly contribute to this hyperalgesia.