Permanent effects of neonatally administered resiniferatoxin in the rat.
We have previously demonstrated that resiniferatoxin functions in adult rats as an ultrapotent analog of capsaicin. In adults, capsaicin excites and then desensitizes a specific population of sensory neurons; when administered to neonates capsaicin causes degeneration of these neurons. We report here that treatment of newborn rats with resiniferatoxin caused a substantial (47%) loss of dorsal root ganglia neurons in adults and an almost complete loss of calcitonin gene related peptide-like immunoreactivity in both dorsal root ganglia and gasserian ganglia. The animals were unresponsive to noxious chemical stimuli and showed marked diminution (88%) of their neurogenic inflammatory response. Resiniferatoxin was at least 2 orders of magnitude more potent than capsaicin for inducing neurodegeneration in the neonates. Specific resiniferatoxin binding, thought to represent capsaicin receptors, decreased 80-90% in membranes from dorsal root ganglia and 50-70% in membranes from gasserian ganglia of adult rats treated neonatally with resiniferatoxin. The affinity for the residual binding decreased. We speculate that subpopulations of sensory neurons differ in susceptibility to neonatal resiniferatoxin treatment. Resiniferatoxin promises to be a useful probe to explore mechanisms of sensorotoxin-induced degeneration for subpopulations of capsaicin-sensitive sensory neurons.
Szallasi
A
A
Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892.
Szallasi
Z
Z
Blumberg
P M
PM
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D002211:Capsaicin / Q000494:pharmacology; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D009479:Neuropeptides; D002211:Capsaicin