RESUMEN
Neuropeptides play important modulatory roles throughout the nervous system, functioning as direct effectors or as interacting partners with other neuropeptide and neurotransmitter systems. Limbic brain areas involved in learning, memory and emotions are particularly rich in neuropeptides. This review will focus on the amygdala, a limbic region that plays a key role in emotional-affective behaviors and pain modulation. The amygdala is comprised of different nuclei; the basolateral (BLA) and central (CeA) nuclei and in between, the intercalated cells (ITC), have been linked to pain-related functions. A wide range of neuropeptides are found in the amygdala, particularly in the CeA, but this review will discuss those neuropeptides that have been explored for their role in pain modulation. Calcitonin gene-related peptide (CGRP) is a key peptide in the afferent nociceptive pathway from the parabrachial area and mediates excitatory drive of CeA neurons. CeA neurons containing corticotropin releasing factor (CRF) and/or somatostatin (SOM) are a source of long-range projections and serve major output functions, but CRF also acts locally to excite neurons in the CeA and BLA. Neuropeptide S (NPS) is associated with inhibitory ITC neurons that gate amygdala output. Oxytocin and vasopressin exert opposite (inhibitory and excitatory, respectively) effects on amygdala output. The opioid system of mu, delta and kappa receptors (MOR, DOR, KOR) and their peptide ligands (ß-endorphin, enkephalin, dynorphin) have complex and partially opposing effects on amygdala function. Neuropeptides therefore serve as valuable targets to regulate amygdala function in pain conditions. This article is part of the special issue on Neuropeptides.
Asunto(s)
Afecto/fisiología , Amígdala del Cerebelo/metabolismo , Dolor Crónico/metabolismo , Dolor Crónico/psicología , Neuropéptidos/metabolismo , Animales , Hormona Liberadora de Corticotropina/metabolismo , Emociones/fisiología , Humanos , Neurofisinas/metabolismo , Oxitocina/metabolismo , Precursores de Proteínas/metabolismo , Vasopresinas/metabolismoRESUMEN
Neuroplastic changes in the amygdala account for emotional-affective aspects of pain and involve neuropeptides such as calcitonin gene-related peptide and corticotropin-releasing factor. Another neuropeptide system, central arginine vasopressin, has been implicated in neuropsychiatric disorders, but its role in pain-related emotional expression and neuroplasticity remains to be determined. Here, we tested the hypothesis that arginine vasopressin in the amygdala contributes to pain-related emotional-affective responses, using stereotaxic applications of arginine vasopressin and antagonists for G-protein coupled vasopressin V1A and oxytocin receptors in adult male Sprague-Dawley rats. In normal animals, arginine vasopressin increased audible and ultrasonic vocalizations and anxiety-like behavior (decreased open-arm preference in the elevated plus maze). The facilitatory effects were blocked by a selective V1A antagonist (SR 49059, Relcovaptan) but not by an oxytocin receptor antagonist (L-371,257). L-371,257 had some facilitatory effects on vocalizations. Arginine vasopressin had no effect in arthritic rats (kaolin/carrageenan knee joint pain model). SR 49059 inhibited vocalizations and anxiety-like behavior (elevated plus maze) in arthritic, but not normal, rats and conveyed anxiolytic properties to arginine vasopressin. Arginine vasopressin, SR 49059, and L-371,257 had no significant effects on spinal reflexes. We interpret the data to suggest that arginine vasopressin through V1A in the amygdala contributes to emotional-affective aspects of pain (arthritis model), whereas oxytocin receptors may mediate some inhibitory effects of the vasopressin system.