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)
White
D M
DM
Department of Medicine, University of California, San Francisco 94143.
Levine
J D
JD
D015761:4-Aminopyridine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D005839:Gentamicins / Q000494:pharmacology; D006614:Hindlimb / Q000294:innervation; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010525:Peripheral Nerves / Q000502:physiology*; D010812:Physical Stimulation; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012604:Scorpion Venoms / Q000494:pharmacology; D013110:Sphingosine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D005839:Gentamicins; D009498:Neurotoxins; D015221:Potassium Channels; D012604:Scorpion Venoms; C052567:noxiustoxin; D015761:4-Aminopyridine; D013110:Sphingosine; D013755:Tetradecanoylphorbol Acetate