Upregulation of the hypothalamo-neurohypophysial system and activation of vasopressin neurones attenuates hyperalgesia in a neuropathic pain model rat

Abstract

Arginine vasopressin (AVP) is a hypothalamic neurosecretory hormone well known as an antidiuretic, and recently reported to be involved in pain modulation. The expression kinetics of AVP and its potential involvement in the descending pain modulation system (DPMS) in neuropathic pain (NP) remains unclear. We investigated AVP expression and its effects on mechanical and thermal nociceptive thresholds using a unilateral spinal nerve ligation (SNL) model. All rats with SNL developed NP. Intensities of enhanced green fluorescent protein (eGFP) in the supraoptic and paraventricular nuclei, median eminence, and posterior pituitary were significantly increased at 7 and 14 days post-SNL in AVP-eGFP rats. In situ hybridisation histochemistry revealed significantly increased AVP mRNA expression at 14 days post-SNL compared with the sham control group. The chemogenetic activation of AVP neurones significantly attenuated mechanical and thermal hyperalgesia with elevated plasma AVP concentration. These analgesic effects were suppressed by pre-administration with V1a receptor antagonist. AVP neurones increased the neuronal activity of serotonergic dorsal raphe, noradrenergic locus coeruleus, and inhibitory interneurones in the spinal dorsal horn. These results suggest that the hypothalamo-neurohypophysial system of AVP is upregulated in NP and activated endogenous AVP exerts analgesic effects via the V1a receptors. AVP neurones may activate the DPMS.

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“…AVP is produced in two distinct populations of neuroendocrine neurons in the PVH of the human hypothalamus: magnocellular AVP neurons and parvocellular corticotropin-releasing factor (CRF)/AVP co-expressing neurons (18). Chronic pain increases AVP secretion in the PVH of rodents, in addition to chronic restraint stress and glucocorticoid deficiency (19,20). Baba et al reported that neuropathic pain increases the mRNA levels of AVP not only in the magnocellular PVH and SON but also in the parvocellular PVH (19).…”

“…Chronic pain increases AVP secretion in the PVH of rodents, in addition to chronic restraint stress and glucocorticoid deficiency (19,20). Baba et al reported that neuropathic pain increases the mRNA levels of AVP not only in the magnocellular PVH and SON but also in the parvocellular PVH (19). AVP in the parvocellular PVH is involved in the impairment of water diuresis and hyponatremia via regulation of renal aquaporin-2 protein levels and localization in epithelial cells of the renal collecting ducts in glucocorticoid deficiency (21).…”