CHARACTERIZATION AND BIOCHEMICAL MECHANISMS OF THE NEUROTOXIC ACTIONS OF CAPSAICIN
AuthorMILLER, MATTHEW STEVEN.
KeywordsCapsaicin -- Toxicology.
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PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractCapsaicin, the primary pungent component of hot peppers, produced chemogenic and thermal antinociception within two hours after administration to adult guinea pigs (2-8 mg/kg). Antinociception lasted in excess of 10 days. In addition, in somewhat higher doses (4-25 mg/kg s.c.) capsaicin also depleted the putative peptide neurotransmitter, substance P, from primary afferent neurons. Depletion of substance P by capsaicin did not occur until at least one day after capsaicin treatment and the onset of antinociception. Antinociception produced by capsaicin appeared to be a result of bioactivation and covalent binding of capsaicin to the distal ends of sensory neurons. Capsaicin depleted substance P from sensory nerves by inhibiting the rate of substance P synthesis by 48 percent. Inhibition of substance P synthesis by capsaicin occurred with some degree of specificity as the rate at which total protein was synthesized was unchanged. The biochemical mechanism by which capsaicin altered substance P synthesis involved alterations in the retrograde axoplasmic transport of nerve growth factor. Doses of capsaicin which depleted substance P also inhibited the retrograde axoplasmic transport of nerve growth factor. Inhibition of the retrograde transport of nerve growth factor by capsaicin preceded substance P depletion. Supplementation of guinea pigs with mouse nerve growth factor completely prevented capsaicin-induced substance P depletion. It is concluded that capsaicin depletes substance P from primary afferent neurons of the adult guinea pig by altering the availability of NGF. The data support a role for NGF in the normal maintenance of neuropeptide levels in some sensory neurons in the adult animal.
Degree ProgramPharmacology & Toxicology