Differential contributions of vasopressin V1A and oxytocin receptors in the amygdala to pain-related behaviors in rats

Abstract

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.

Kappa opioid receptors in the central amygdala modulate spinal nociceptive processing through an action on amygdala CRF neurons

“…The contribution of the amygdala to sensory aspects of pain such as hypersensitivity in pain models is less clear. Manipulations of amygdala activity provided evidence for dual pro-and anti-nociceptive effects [4,[17][18][19][20][21][22][23][24][25][26] but others had little, if any effect on hypersensitivity [15,16,[27][28][29][30][31][32]. The current view is that distinct amygdala circuits and cell types serve different functions related to different aspects of pain.…”

Small conductance calcium activated potassium (SK) channel dependent and independent effects of riluzole on neuropathic pain-related amygdala activity and behaviors in rats

“…Vocalizations were measured as described previously (see (Cragg et al, 2016; Han et al, 2005; Kiritoshi et al, 2016; Medina et al, 2014; Neugebauer et al, 2007; Thompson et al, 2015). Rats were briefly anesthetized with isoflurane (2–4%) and lightly restrained in a custom designed recording chamber (US Patent 7,213,538) placed at a fixed distance from the detectors.…”

“…Reverse microdialysis for drug application into specific brain regions is a well-established technique in our laboratory, and experiments were conducted as described previously (for recent publications, see (Cragg et al, 2016; Kiritoshi et al, 2016; Thompson et al, 2015)). This approach was used instead of drug injection because it does not result in a volume effect and allows for drug concentration to be maintained throughout drug administration (Stiller et al, 2003).…”

Oxytocin Signaling in Pain: Cellular, Circuit, System, and Behavioral Levels

“…Accordingly, Han and Yu demonstrated an analgesic effect of intra-CeA infusion of oxytocin (Han and Yu 2009). In the same supportive line of evidence, Neugebauer's lab recently published interesting results suggesting that the CeA OTR mediates some analgesic tone in an arthrisis pain model (Cragg et al 2016).…”