Vanilloid receptor loss in rat sensory ganglia associated with long term desensitization to resiniferatoxin.
A dose-dependent loss of vanilloid receptors (specific [3H]resiniferatoxin binding sites) was found in sensory ganglia of rats 24 h after s.c. administration of resiniferatoxin (RTX), an ultrapotent capsaicin analog. This receptor loss displayed an ED50 of 30 micrograms/kg both in dorsal root and trigeminal ganglia; the ED50 was 6-fold higher than the ED50 for loss of the neurogenic inflammatory response and 30-60-fold higher than the ED50 for desensitization in the standard eye-wiping (chemogenic pain) response. The receptor loss appeared later (24 h) than the loss of the physiological responses (6 h) and showed modest recovery (to 20-30% of control levels) over the following 4 weeks. This vanilloid receptor loss may represent a novel, specific mechanism for vanilloid-induced chronic desensitization.
Szallasi
A
A
Laboratory of Cellular Carcinogenesis and Tumor Promotion, National Cancer Institute, Bethesda, MD 20892.
Blumberg
P M
PM
D000818:Animals; D001665:Binding Sites; D004224:Diterpenes / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007249:Inflammation; D007700:Kinetics; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
D004224:Diterpenes; D011955:Receptors, Drug; C024353:resiniferatoxin