Intraventricular capsaicin: alterations in analgesic responsivity without depletion of substance P.
Both systemic and intrathecal capsaicin release and deplete substance P from primary sensory afferents and induce prolonged chemical and thermal analgesia. Given the existence of efferents containing substance P together with a pain-inhibitory serotoninergic pathway, the present study investigated the effects of intraventricular capsaicin upon basal nociception, analgesic responsivity to opiates and substance P immunoreactivity. Following treatment with capsaicin at doses of 25, 50 and 100 micrograms or with vehicle, alterations in basal rodent flinch-jump thresholds as well as analgesic responses to 5 and 2.5 mg/kg of morphine were measured over a post-injection time course. Tissues were then processed for immunocytochemistry for substance P according to the unlabelled antibody peroxidase antiperoxidase procedure. Decreases were noted in jump thresholds only at 72 h following capsaicin. Moreover, morphine analgesia at both doses was attenuated in dose-dependent fashion following capsaicin with the highest dose (100 micrograms) producing a significant decrease in analgesic efficacy. Substance P-like immunoreactivity in capsaicin-treated rats was not appreciably depleted compared with vehicle controls in the substantia gelatinosa of the spinal cord and V cranial nerve, the raphe magnus and periaqueductal gray, the medullary, pontine and mesencephalic reticular formation, the substantia nigra, the corpus striatum and the central nucleus of the amygdala. By contrast, substance P-like immunoreactivity appeared to increase in the medial nucleus of the amygdala. In the absence of depletion of substance P immunoreactivity by the intraventricular capsaicin, the observed alterations in opiate analgesic responses may possibly be due to alterations in other transmitters or peptide systems.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D012684:Sensory Thresholds; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013373:Substance P / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects*
D005231:Fatty Acids, Unsaturated; D013373:Substance P; D009020:Morphine; D002211:Capsaicin