Effects of Systemic Capsaicin Treatment on TRPV1 and Tachykinin NK1 Receptor Distribution and Function in the Nucleus of the Solitary Tract of the Adult Rat

Vanilloids, including capsaicin and resiniferatoxin, have been identified as potential novel anti-inflammatory and analgesic compounds. We have previously shown that systemic capsaicin administration in neonatal rats evokes profound long term alterations in transient receptor potential vanilloid 1 (TRPV1)- and neurokinin 1 receptor (NK1)-mediated respiratory responses in the commissural nucleus of the solitary tract (cNTS). Whether this is effect of capsaicin is unique to developmentally immature animals is unknown. Therefore, in the present study, we investigated the effects of systemic capsaicin administration in adult rats on NK1 receptor binding sites, TRPV1- and NK1-immunoreactivity and function in the cNTS. Microinjection of capsaicin (1 nmol) or resiniferatoxin (75 pmol) into the cNTS of vehicle-pretreated rats produced a profound bradypnoea (maximum change, -45 breaths min-1) and a small increase in tidal volume (VT). Similarly, microinjection of the selective NK1 receptor agonists, [Sar9,Met(O2)11]-substance P (66 pmol) and septide (20 pmol), decreased respiratory frequency and increased VT. Thirteen-18 days after systemic administration of capsaicin (125 mg kg-1 s.c.), the bradypnoeic responses to both capsaicin and resiniferatoxin were absent (p<0.05), indicative of sensory neuron ablation/ desensitisation. Systemic capsaicin pre-treatment significantly (p<0.05) reduced the density of both [125I]-Bolton Hunter substance P binding sites (NK1 receptors) and NK1 receptor immunoreactivity in the cNTS, but but did not alter the respiratory responses evoked by microinjection of [Sar9,Met(O2)11]-substance P and septide into this region. These studies show that systemic capsaicin administration reduces NK1 receptor density in the cNTS, without adversely affecting NK1 receptor function at this site. We speculate that adult rats may be more resistant than neonatal rats to the neuroplastic effects of systemic capsaicin administration.