Characterization of the peptide and sensory neurotoxic effects of capsaicin in the guinea pig.
The effects of capsaicin, the major pungent ingredient of hot peppers, were assessed on sensory neuron neuropeptide levels and on sensory function in the adult guinea pig. Systemic doses of capsaicin as low as 2.5 mg/kg depleted substance P (SP) in dorsal roots plus ganglia (DRG) whereas a 10-mg/kg dose depleted the peptide maximally in DRG and in the dorsal spinal cord. High doses of capsaicin had no consistent effects on levels of cholecystokinin (CCK), vasoactive intestinal polypeptide, or somatostatin, although a transient decrease in CCK levels was observed 4 days after dosing. 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 10 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. 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 effect of the agent on SP-containing primary afferent neurons.
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology* / Q000633:toxicity; D002766:Cholecystokinin / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D009020:Morphine / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009422:Nervous System Diseases / Q000139:chemically induced; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects; D010525:Peripheral Nerves / Q000187:drug effects* / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
D009419:Nerve Tissue Proteins; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D013004:Somatostatin; D009020:Morphine; D002766:Cholecystokinin; D002211:Capsaicin