Serotonin-gated inward currents are three times more frequent in rat hairy skin sensory afferents than in those innervating the skeletal muscle

Tight whole-cell patch clamp was performed in 191 DiI (1,1′-dioctadecyl-3,3,3′3′-tetramethylindocarbocyanine perchlorate) retrogradely labeled rat sensory afferents from skin shoulders (n = 93) and biceps femoris muscles (n = 98). 5-HT-gated inward currents were evoked with 50-µM serotonin (5-HT; 5-hydroxytryptamine), and their frequency and current densities were compared between skin and skeletal muscle sensory afferents. To evaluate if 5-HT-gated inward currents coexist with other ligand-gated currents, the skin and skeletal muscle sensory afferents were also sequentially exposed to external solution at pH 6.8, ATP (50 µM), and capsaicin (1 µM). 5-HT evoked inward currents in 72% (67 of 93) of hairy skin sensory afferents and in only 24% (24 of 98) of skeletal muscle sensory afferents, and this difference was statistically significant (p < 0.0000, chi-square test). The current densities obtained in hairy skin and skeletal muscle sensory afferents were not significantly different. They were −45.8 ± 7.7 and −32.4 ± 10.5 pA/pF, respectively (mean ± SEM, p < 0.30734). These results indicate that 5-HT-gated inward currents are three times more frequently evoked in small- to medium-sized sensory afferents (25–40 µm) innervating the hairy skin than on those innervating the skeletal muscle. When cells were gathered in two clusters, the difference was four times larger in the small-sized cluster (25–32 µm) and two times larger in the medium-sized cluster (33–40 µm). The results can be explained if the superficial somatic (cutaneous) nociceptive system is more exposed than the deep somatic nociceptive system (musculoskeletal) to physical and chemical stimuli inducing 5-HT-mediated inflammatory pain.