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Analysis of the distribution of spinal NOP receptors in a chronic pain model using NOP‐eGFP knock‐in mice
Author(s) -
Ozawa Akihiko,
Brunori Gloria,
Cippitelli Andrea,
Toll Nicholas,
Schoch Jennifer,
Kieffer Brigitte L,
Toll Lawrence
Publication year - 2018
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.14225
Subject(s) - nop , nociceptin receptor , nociception , allodynia , spinal cord , neuropathic pain , hyperalgesia , opioid receptor , receptor , medicine , chemistry , opioid , pharmacology , anesthesia , opioid peptide , psychiatry
Background and Purpose The nociceptin/orphanin FQ opioid peptide (NOP) receptor system plays a significant role in the regulation of pain. This system 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 intrathecal nociceptin/orphanin FQ (N/OFQ) in chronic neuropathic pain. Experimental Approach We used immunohistochemistry to determine changes in NOP receptor distribution triggered by spinal nerve ligation (SNL) using NOP‐eGFP knock‐in mice. Antinociceptive effects of intrathecal N/OFQ on SNL‐mediated allodynia and heat/cold hyperalgesia were assessed in wild‐type mice. Key Results NOP‐eGFP immunoreactivity was decreased by SNL in the spinal laminae 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 dorsal root ganglion (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.