Involvement of the Nociceptin/Orphanin FQ-NOP receptor system in the ventrolateral periaqueductal gray following mechanical allodynia in chronic pain

AimsIt has been well documented that ventrolateral periaqueductal gray (vlPAG) matter is a crucial component of the descending pain modulatory system in the chronic pain condition. The aim of the present study was to identify the role of the vlPAG Nociceptin/Orphanin FQ/NOP receptor system in allodynia, a nociceptive behavioral response associated with chronic pain.Main methodsWe used two animal models of persistent pain: chronic constriction injury (CCI) and inflammation induced by carrageenan. In each, Nociceptin/Orphanin FQ transmission was abolished using UFP-101, a selective NOP receptor antagonist, which was injected into the vlPAG at a dose of 18 µg/1 µl/rat.Key findingsWe found that treatment with the NOP antagonist reversed the decrease in allodynic threshold in CCI rats fourteen days after the ligature, which was the timepoint of the greatest reduction in threshold. Moreover, UFP-101 administered immediately prior to or 2 h after intra plantar (i.pl.) carrageenan injection prevented or reversed, respectively, allodynic behavior in rats with inflammation.SignificanceOur findings support the hypothesis that the endogenous Nociceptin/Orphanin FQ/NOP receptor system is tonically active at the vlPAG level during neuropathic states or carrageenan inflammation.