Hypocretin/orexin and nociceptin/orphanin FQ coordinately regulate analgesia in a mouse model of stress-induced analgesia

Knock-In Mice with NOP-eGFP Receptors Identify Receptor Cellular and Regional Localization

“…2C), as has been demonstrated in DRG neurons and other neuronal cells prepared from wild-type mice (Xie et al, 2008;Murali et al, 2012). Patch-clamp electrophysiology was also conducted on hippocampal slices.…”

“…Studies are underway to identify the NOP-containing cells in the VTA to determine the mechanism by which NOP and -receptor activation have such different outcomes. N/OFQ also blocks a cocaine-induced increase in extracellular dopamine in the NAc when reverse dialized into the NAc (Vazquez-DeRose et al, 2013), blocks release of hypocretin/orexin from hypocretin-containing cells in the lateral hypothalamus (Xie et al, 2008), and acts in opposition to CRF in the amygdala (Ciccocioppo et al, 2004). All of these actions can attenuate drug reward, and it might be the presence of NOP receptors in so many regions involved in drug abuse and stressinduced relapse that renders N/OFQ and small molecule NOP receptor agonists so effective in blocking CPP of so many abused drugs (Kotlinska et al, 2003;Kuzmin et al, 2003;Sakoori and Murphy, 2004).…”

Orexin/Hypocretin: A Neuropeptide at the Interface of Sleep, Energy Homeostasis, and Reward System

“…Orexin neurons were hyperpolarized by nociceptin/orphanin FQ (N/OFQ), which is a neuropeptide implicated in blocking SIA (Xie et al, 2008). Coadministration of orexin A overcame N/OFQ inhibition of SIA in mice (Xie et al, 2008). These results suggest that the orexin neurons regulate SIA and its effects might be modulated by N/OFQ.…”

“…Orexin knockout mice presented less SIA than wild-type mice . Orexin neurons were hyperpolarized by nociceptin/orphanin FQ (N/OFQ), which is a neuropeptide implicated in blocking SIA (Xie et al, 2008). Coadministration of orexin A overcame N/OFQ inhibition of SIA in mice (Xie et al, 2008).…”

Overview of orexin/hypocretin system

“…Furthermore, the orexin system has been also implicated in analgesia. Especially, the corticotropin-releasing factor (CRF) and nociceptin/orphanin FQ (N/OFQ) systems modulate orexin neurons in a coordinated manner to regulate stress-induced analgesia, a key component of the defensive behavioral "fight or flight" response (Xie et al, 2008).…”