Involvement of a chemokine, MCP-1, has been demonstrated in the mechanical hyperalgesia after peripheral nerve injury or inflammation. Increase of calcium influx in cultured dorsal root ganglion (DRG) neurons and IB4 (+) neuron mediated decrease in nocifensive mechanical withdrawal threshold by MCP-1 (Bogen et al., 2009) have been reported so far. However, there has been no study about the effects of MCP-1 on the peripheral afferent terminals. The present study aimed to examine the effect of MCP-1 on the responses of the mechanosensitive C-afferents using in vitro single fiber recordings from skin-saphenous nerve preparations excised from euthanized rats. Effects of MCP-1 were examined with respect to sensitivity to α, β-methylene ATP (metATP), which is considered to be an indicator of IB4 (+) neurons. A total of 53 cutaneous C-fiber afferents were recorded. Thirty minutes application of MCP-1 100 ng/ml (n = 18) to the receptive field elicited excitation in 50% of recorded fibers in MCP-1 group, whereas 11% in PBS group (p < 0.01, Fisher's exact probability test). MCP-1 significantly increased the response magnitude to mechanical stimulation in metATP insensitive fibers (p < 0.01, repeated measured ANOVA), but not in metATP sensitive fibers. The incidence of the heat sensitive fibers was decreased with lowered response threshold in the MCP-1 treated group. To investigate the cellular mechanisms we examined mechanical sensitization by MCP-1 in cultured DRG neurons by measuring mechanically activated currents using patch clamp method, but could not observe increase of the currents. These results may suggest a possibility that some cells other than neurons are necessary for sensitization by MCP-1.
In summary, the present results demonstrated MCP-1 excites and sensitizes to mechanical stimulation mechanosensitive C-fiber afferents in the rat skin, but did not support an involvement of IB4 (+) afferents in MCP-1 effects.
Present address of A.K. is Dept. Physiol., Nihon Univ. Sch. Dent., Tokyo, Japan.