Axonal thermosensitivity and mechanosensitivity of cutaneous afferent neurons

We hypothesized that cutaneous afferent myelinated fibers (A-fibers) and afferent unmyelinated fibers (C-fibers) respond to the same natural stimuli applied to their axons as to their terminals in the skin. In anesthetized rats, activity was recorded from afferent axons in strands isolated proximally from the sural nerve. Mechanical, cold or heat stimuli were applied to the skin or along a 15-mm length of the distal sural nerve. One-hundred and eighteen A-fibers and 109 C-fibers were characterized by their conduction velocity and/or shape of their action potentials, and by their responses to natural stimulation of the skin. Then, these fibers were tested for their responses to the same stimuli applied to the nerve. In some cases, the nerve was crushed distally after the nerve fibers had been characterized by their responses to physiological stimulation of the skin, and the responses to stimuli applied to the nerve proximal to the lesion were tested again. Almost all non-nociceptive cold-sensitive (type 1) C-fibers (97%) could be activated by cold stimuli applied to the nerve. Of nociceptive cold-sensitive (type 2) C-fibers, 39% were activated by cold stimuli applied to the nerve. Furthermore, 34% of heat-sensitive C-fibers could be activated by heating the nerve. In contrast, only 2-4% of mechanosensitive A-fibers and C-fibers responded to mechanical stimuli applied to the nerve. In conclusion, cold and heat sensitivity of cutaneous afferent neurons is not restricted to their terminals in the skin, but often extends along the axons in the nerve. Mechanosensitivity is restricted to the afferent endings in the skin.