Duration of desensitization and ultrastructural changes in dorsal root ganglia in rats treated with resiniferatoxin, an ultrapotent capsaicin analog.
We have previously demonstrated resiniferatoxin (RTX) to be an ultrapotent analog of capsaicin. Like capsaicin, RTX initially induces neurogenic inflammation, pain, and hypothermia and then causes desensitization of these responses. We examine here the duration of desensitization following acute treatment with the maximal tolerated dose of RTX. Desensitization to neurogenic inflammation began to diminish by 7 days, whereas desensitization to pain and to induction of hypothermia persisted for several weeks. Interestingly, a partial hypothermic response returned within 24 h if challenge was with RTX at 500-fold its ED50 for control animals; the animals, moreover, maintained their ability to thermoregulate in a hot environment. The time course of the morphological changes--ultrastructure and calcium staining--of dorsal root ganglion neurons was examined in parallel. The ultrastructural changes were evident by 4 h and persisted for the duration of the experiments. Limited calcium staining was visible at 12 and 24 h after treatment but then diminished. In comparison with capsaicin treatment, RTX caused more long-lasting desensitization as well as a distinct spectrum of response.
Szallasi
A
A
Molecular Mechanisms of Tumor Promotion Section, National Cancer Institute Bethesda, MD 20892.
Joo
F
F
Blumberg
P M
PM
D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D002211:Capsaicin / Q000031:analogs & derivatives*; D004224:Diterpenes / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005727:Ganglia, Spinal / Q000502:physiology* / Q000648:ultrastructure; D007035:Hypothermia / Q000139:chemically induced; D008928:Mitochondria / Q000187:drug effects / Q000648:ultrastructure; D009475:Neurons, Afferent / Q000502:physiology* / Q000648:ultrastructure; D051381:Rats
D004224:Diterpenes; C024353:resiniferatoxin; D002211:Capsaicin