Evidence that substance P selectively modulates C-fiber-evoked discharges of dorsal horn nociceptive neurons.
Previous studies suggest that the undecapeptide substance P (SP) functions as a primary afferent neurotransmitter or neuromodulator of nociception which may mediate the slow temporal summation ('windup') of discharges of dorsal horn nociceptive neurons elicited by repetitive stimulation of C-afferents. The present study tested this hypothesis by investigating the effects of local spinal application of SP and an SP antagonist. [D-Pro2,D-Trp7,9]-SP (DPDT), on A- and C-fiber-evoked firing of dorsal horn neurons in an intact, urethane-anesthetized rat preparation. Extracellular single unit recordings from both wide dynamic range and nociceptive specific neurons during controlled repetitive electrical stimulation of the ipsilateral hind paw indicated that SP enhanced C-evoked firing in an apparent dose-related manner (100 greater than 20 = 4 nmol), whereas DPDT inhibited C-evoked discharges with an apparent bell-shaped dose-response (20 greater than 100 = 4 nmol). Neither agent significantly altered either A-evoked or spontaneous activity. In agreement with previous investigators, morphine sulfate also selectively inhibited C-fiber-evoked firing without altering A-fiber-mediated activity, validating the selectivity of our system. These findings provide additional evidence that SP functions as a neuromodulator of primary afferent nociception, and further suggest that the effects of SP are selective to nociceptive transmission mediated by C-fibers.
Department of Physiology, Medical College of Virginia, Virginia Commonwealth University, Richmond.
D E
DE
Kellstein
D D
DD
Price
R L
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Hayes
D J
DJ
Mayer
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009412:Nerve Fibers / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*
D013373:Substance P; D009020:Morphine; C032132:substance P, prolyl(2)-tryptophan(7,9)-