Capsaicin-induced local effector responses, autonomic reflexes and sensory neuropeptide depletion in the pig.
Systemic capsaicin pretreatment (total cumulative dose 50 mg/kg administered s.c. over 2h) was performed in pigs under pentobarbitone anaesthesia and the effects on sensory and sympatho-adrenal mechanisms were examined acutely and 2 days after treatment. During pretreatment with capsaicin, pronounced sensory and sympatho-adrenal activation were noticed. This resulted in a several-fold increase in the systemic arterial plasma levels of calcitonin gene-related peptide (CGRP), neurokinin A (NKA), noradrenaline (NA), adrenaline (Adr) and neuropeptide Y (NPY), and a slight increase (39%) in plasma cortisol. Simultaneously, there was marked tachycardia, an increase in blood pressure, total skin erythema and some bronchoconstriction, all lasting for about 30 min. Upon repeated injections tachyphylaxis was observed. 2 days after capsaicin pretreatment, basal plasma levels of the neuropeptides, catecholamines and cortisol as well as basal cardiovascular and pulmonary parameters were similar in control and capsaicin-treated pigs. The tissue content of CGRP and NKA was reduced by 50-65% in the airways and by 80-90% in the skin 2 days after capsaicin pretreatment. In contrast, the CGRP content was unchanged or increased (by 195%) in the nodose and spinal ganglia, respectively. The corresponding tissue levels of vasoactive intestinal polypeptide (VIP) and NPY were basically unchanged in capsaicin-treated pigs. A bolus injection of capsaicin (1 mg/kg i.v.) in control animals resulted in a marked increase in plasma catecholamines and NPY, concomitant with elevation in blood pressure and heart rate. These effects were preceded by an initial bradycardia and decrease in blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Alving
K
K
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Matran
R
R
Lundberg
J M
JM
D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D001798:Blood Proteins / Q000378:metabolism; D016084:Bronchoconstriction / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000097:blood / Q000378:metabolism; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology*; D002395:Catecholamines / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006854:Hydrocortisone / Q000097:blood; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D015288:Neurokinin A / Q000097:blood / Q000378:metabolism; D009478:Neuropeptide Y / Q000097:blood / Q000378:metabolism; D009479:Neuropeptides / Q000097:blood / Q000378:metabolism*; D012018:Reflex / Q000187:drug effects* / Q000502:physiology; D013552:Swine; D013997:Time Factors; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects
D001798:Blood Proteins; D002395:Catecholamines; D009478:Neuropeptide Y; D009479:Neuropeptides; D014660:Vasoactive Intestinal Peptide; D015288:Neurokinin A; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D006854:Hydrocortisone