Yudin Y. Algogenic effect of RFa-related peptides on the peripheral sensory fibers: evidence in vitro and in vivo

This work is devoted to investigation of peripheral action of RFa peptides. Here we demonstrate that RFa-related peptides powerfully excite the majority of C-fibres: 82 % of 60 tested fibres with the conduction velocity below 2 m/s responded with long-lasting discharges to the application of peptides (20 mM). Amiloride reversibly inhibited the excitatory effects of RFa peptides in 21 out of 38 fibers, in another 17 cases it was uneffective. Thus, powerful excitatory action of RFa-related peptides cannot be interpreted solely in terms of their interaction with ASICs. Subcutaneous injections of the NPSF into the n.saphenous innervation area result in a nociceptive behavior in ASIC3-/- and wild-type C57BL/6J mice. There is no significant difference in the total time of licking of injected paw in the ASIC3-/- (194±22 s) and C57BL/6J (227±25 s) animals. Thus peripheral algogenic effects of NPSF cannot be explained only in terms of their action on the ASIC3 channels.