Nociceptin and its receptor in rat dorsal root ganglion neurons in neuropathic and inflammatory pain models: implications on pain processing

Nociceptin (NC), by activating its receptor, the opioid receptor-like 1 (ORL1) receptor, exerts an effect on a number of functions in the nervous system including locomotion, learning and memory, and processing of pain signals. Data on the expression of NC and ORL1 receptor in dorsal root ganglion (DRG) neurons and on its modulation after nerve injury and inflammation are controversial. We therefore sought to investigate the immunoreactivity (IR) of NC and ORL1 receptor in DRG neurons in two pain models, a pure neuropathic pain model, namely partial sciatic nerve transection (PST), and an inflammatory pain model, complete Freund's adjuvant (CFA) injection into the hindpaw. In intact DRG neurons, both NC and ORL1 receptor IR were present in mainly small- and medium-sized neurons, NC IR in 31% and ORL1 receptor IR in 33% of all neuronal profiles. Both NC and ORL1 receptor IR were upregulated 7 days after nerve injury (to 56 and 55%) and inflammation (to 53 and 48%), respectively. Activating transcription factor 3 (ATF3), a neuronal marker of nerve injury, was induced in DRG neurons 7 and 14 days after PST and 7 days after CFA injection. Double labeling with ATF3 revealed expression of NC and ORL1 receptor in intact as well as in injured primary afferent neurons. Thus, NC and the ORL1 receptor may be involved in the modulation of neuropathic and inflammatory pain at the level of the primary afferent neuron.