Title:The Orexinergic (Hypocretin) System and Nociception: An Update to Supraspinal Mechanisms
Volume: 25
Issue: 32
Author(s): Ali Roohbakhsh, Mohaddeseh Sadat Alavi and Hassan Azhdari-Zarmehri*
Affiliation:
- Neuroscience Research Center, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh,Iran
Keywords:
Neuropeptides, orexin, hypocretin, pain, orexin receptors, neuropathic pain.
Abstract: Chronic pain is a multifaceted and complex condition that is divided into somatic,
visceral, and neuropathic pain. Although opioids and nonsteroidal anti-inflammatory drugs
cause analgesia and are effective in the treatment of chronic pain, their utility is hampered by
side effects, abuse potential, and development of tolerance to their pain-relieving effects. So,
finding alternative analgesics with good efficacy and low side effects is of great interest and
the orexinergic system is a potential candidate. Orexin-A and -B are exclusively expressed in
the lateral hypothalamus and are involved in the feeding, sleep/wake cycle, cardiovascular
function, hormone secretion, seizure, and pain modulation. Orexin peptides and their receptors
have been proposed as opportunities for developing analgesic drugs. In experimental studies,
orexin peptides induce analgesia that is comparable to morphine. Furthermore, there is
evidence that orexin receptors 1 and 2 participate in responsiveness to both stressful stimuli
and pain. Thus, direct and indirect activation of the orexinergic system is a new therapeutic
approach to pain control. This article will review the most recent and important studies describing
the role of orexins in pain modulation.
