Dissecting the spinal NOP receptor distribution under a chronic pain model using NOP-eGFP knock-in mice.

TitleDissecting the spinal NOP receptor distribution under a chronic pain model using NOP-eGFP knock-in mice.
Publication TypeJournal Article
Year of Publication2018
AuthorsOzawa A, Brunori G, Cippitelli A, Toll N, Schoch J, Kieffer BL, Toll L
JournalBr J Pharmacol
Date Published2018 Mar 26
ISSN1476-5381
Abstract

BACKGROUND AND PURPOSE: The Nociceptin/orphanin FQ Opioid Peptide (NOP) receptor system plays a significant role in the regulation of pain, and functions differently in the spinal cord and brain. The mechanism by which the NOP receptor agonists regulate pain transmission in these regions is not clearly understood. Here we investigate the peripheral and spinal NOP receptor distribution and antinociceptive effects of intrathecally (i.t) administered nociceptin/orphanin FQ (N/OFQ) under chronic neuropathic pain state.EXPERIMENTAL APPROACH: We performed immunohistochemistry to determine changes in NOP receptor distribution triggered by spinal nerve ligation (SNL) using NOP-eGFP knock-in mice. Experiments were also carried out with wild-type mice to investigate i.t. N/OFQ antinociceptive effect on SNL-mediated allodynia and heat/cold hyperalgesia.KEY RESULTS: We observed a decrease in NOP-eGFP immunoreactivity mediated by SNL in the spinal lamina I and II outer, regions that mediate noxious heat stimuli. In contrast, immunoreactivity of NOP-eGFP was unchanged in the ventral border of lamina II inner, which is an important region for the development of allodynia. NOP-eGFP expression was also decreased in a large number of primary afferents in the L4 DRG of SNL mice. However, SNL mice showed increased sensitivity, compared to sham animals to the effects of i.t administered N/OFQ with respect to mechanical as well as thermal stimuli.CONCLUSIONS AND IMPLICATIONS: Our findings suggest that the spinal NOP receptor system attenuates injury-induced hyperalgesia by direct inhibition of the projection neurons in the spinal cord that send nociceptive signals to the brain and not by inhibiting presynaptic terminals of DRG neurons in the superficial lamina.

DOI10.1111/bph.14225
Alternate JournalBr. J. Pharmacol.
PubMed ID29582417

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