Analgesic Effects of Orexins

Abstract

Orexin A and B (hypocretin 1 and 2) are novel hypothalamic peptides and two receptor subtypes, OX 1 R and OX 2 R, were identified. Orexins are implicated in hyperphagia, arousal, and neuroendocrine and autonomic regulations. Recently, orexins were found to be antinociceptive supraspinally and spinally but sympathetically stimulating. This review summarizes the analgesic effects of orexins reported in acute, inflammatory, and neuropathic pain animal models. The antinociceptive effects of orexins are mediated by OX 1 R, but not opioid receptors. Purinergic P 2X and glycine receptors are supported to be involved in the intrathecal orexin-induced antiallodynia. Endogenous orexins may play a protective role after nociceptive stimulation.A novel family of hypothalamic peptides was identified by de Lecea et al. 1 and named as hypocretins for their structural homology to the gut hormone, secretin. Two peptides, hypocretin 1 and hypocretin 2, derived from a common precursor, prepro-hypocretin, were identified. 1 Six weeks later, Sakurai et al. 2 isolated the same hypothalamic neuropeptides in an independent study that searched for the effective ligands from brain extract acting at a panel of orphan G-protein-coupled receptors. These two peptides were named orexin A and orexin B for their orexigenic (appetite-stimulating) activity when given intracerebroventricularly (i.c.v.). Orexin A and orexin B, consisting of 33 and 28 amino acids, respectively, were matched with hypocretin 1 and hypocretin 2. 3