Different mechanical transduction mechanisms for the immediate and delayed responses of rat C-fiber nociceptors.

1. In this electrophysiological study, action potentials from single C-fibers were recorded in fine filaments teased from the rat saphenous nerve. We evaluated the effect of pharmacological agents on the responses of C-fiber mechanoheat nociceptors (C-MH; n = 53) after sustained suprathreshold and subthreshold stimuli. 2. Sustained suprathreshold mechanical stimuli elicit an immediate burst of activity that quickly adapts to a low-level firing that is maintained during the stimulus. Sustained subthreshold stimuli activate C-MHs after a delay and elicit a constant, low-level firing. 3. Gentamicin, a known suppressor of mechanosensory cell activity, blocked the initial rapid burst response to suprathreshold stimuli (n = 11) but had no effect on the adaptive low-level firing. The latency of the delayed activation of C-MHs induced by sustained subthreshold stimuli was not affected by gentamicin. 4. Sphingosine, a protein kinase inhibitor, increased the latency of the delayed activation of C-MHs (n = 7) to sustained subthreshold stimuli; phorbol 12-myristate 13-acetate (TPA), a protein kinase C activator, decreased the latency of the delayed activation of C-MHs (n = 9); and 4 alpha-phorbol, an inactive isomer of TPA, had no effect on the latency of the delayed activation (n = 7). Sphingosine, TPA, and 4 alpha-phorbol had no affect on the initial burst response induced by suprathreshold stimuli. 5. K+ channel blockers, 4-aminopyridine (n = 9) and noxiustoxin (n = 5), decreased the latency of the delayed activation of C-MHs to sustained subthreshold stimuli but had no effect on the initial burst response of C-MHs to suprathreshold stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)