ALTERATIONS OF SUBSTANCE P-CONTAINING NEURONS AS CLUES TO THE ROLE OF THE PEPTIDE IN THE MAMMALIAN PERIPHERAL NERVOUS SYSTEM.
AuthorBUCK, STEPHEN HENDERSON.
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PublisherThe University of Arizona.
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AbstractThe effects of capsaicin, the major pungent component of hot peppers, were assessed on neuropeptide levels and on sensory function in neonatal and adult rats and in adult guinea pigs. Systemic doses of capsaicin in rats treated while neonates or while adults produced marked depletion of substance P (SP) in dorsal roots plus ganglia (DRG) and in dorsal spinal cord without altering tail-flick latencies in the treated animals. Guinea pigs had several-fold higher levels of SP than did rats in DRG and dorsal cord. In adult guinea pigs, systemic doses of capsaicin as low as 2.5 mg/kg depleted SP in DRG while a 10 mg/kg dose depleted the peptide maximally in DRG (85% decrease) and in the dorsal cord (35% decrease). High doses of capsaicin in guinea pigs had no consistent effects on levels of radioimmunoassayable cholecystokinin (CCK), vasoactive intestinal polypeptide, or somatostatin although a transient decrease in CCK levels was observed four days after dosing in DRG and in ventral cord. A single 5 mg/kg dose of capsaicin rendered animals completely insensitive to chemical irritation of the cornea without affecting sensitivity to noxious heat. Higher doses of capsaicin produced a marked insensitivity to nociceptive and non-nociceptive heat as well as to chemical irritation without affecting other sensory modalities. The SP depletion and sensory deficits produced by a single 50 mg/kg dose of capsaicin were still evident ten weeks later. The pattern of selectivity of the sensory deficits produced by capsaicin differed from that produced by morphine which was active against all forms of nociceptive stimuli. High doses of capsaicin also induced skin lesions and corneal opacities in guinea pigs. The syndrome of sensory effects produced by capsaicin in guinea pigs closely resembles the pattern of sensory deficits in familial dysautonomia, an autosomal recessive disorder in which there is a disappearance of SP from the substantia gelatinosa of the spinal cord. The results indicate that in the guinea pig capsaicin is potent at producing a unique, long-lasting syndrome of peripheral sensory deficits that may result from an action of the compound on SP-containing primary afferent neurons. Capsaicin is a valuable pharmacological tool for investigation of the neurochemistry and neurophysiology of primary afferent neurons and animals treated with the agent may be useful laboratory models of some forms of peripheral neuropathy.
Degree ProgramPharmacology and Toxicology