Effects of systemic capsaicin treatment on TRPV1 and Tachykinin NK(1) receptor distribution and function in the nucleus of the solitary tract of the adult rat

Abstract

Vanilloids including capsaicin and resiniferatoxin (RTX) have been identified as potential novel anti-inflammatory and analgesic compounds. We have previously shown that systemic capsaicin administration to neonatal rats evokes profound long-term alterations in transient receptor potential vanilloid 1 (TRPV1)- and neurokinin 1 (NK(1)) receptor-mediated respiratory responses in the commissural nucleus of the solitary tract (cNTS). Whether this effect of capsaicin is unique to developmentally immature animals is unknown. Therefore, in the present study, we investigated the effects of systemic capsaicin administration to adult rats on NK(1) receptor binding sites, TRPV1 and NK(1) immunoreactivity and function in the cNTS. Microinjection of capsaicin (1 nmol) or RTX (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 NK(1) receptor agonists [Sar(9), Met(O(2))(11)]substance P (SP; 66 pmol) and septide (20 pmol) decreased respiratory frequency and increased VT. Thirteen to 18 days after systemic administration of capsaicin (125 mg·kg(-1) s.c.), the bradypnoeic responses to both capsaicin and RTX were absent (p < 0.05), indicative of sensory neuron ablation/desensitisation. Systemic capsaicin pretreatment significantly (p < 0.05) reduced the density of both [(125)I]Bolton-Hunter SP binding sites (NK(1) receptors) and NK(1) receptor immunoreactivity in the cNTS, but did not alter the respiratory responses evoked by microinjection of [Sar(9), Met(O(2))(11)]SP and septide into this region. These studies show that systemic capsaicin administration reduces NK(1) receptor density in the cNTS without adversely affecting NK(1) 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.