The kappa-opioid receptor is upregulated in the spinal cord and locus ceruleus but downregulated in the dorsal root ganglia of morphine tolerant rats.
As a non-selective agonist of opioid receptors, morphine can also act on the kappa-opioid receptor (KOR) when activating the mu-opioid receptor (MOR) and delta-opioid receptor (DOR). Although previous findings indicate that KOR plays an important role in morphine analgesia and antinociceptive tolerance, the reasons for the paradoxical functions of KOR in analgesia and anti-analgesia responses are still unclear. The aim of this study was to explore the role of the KOR in morphine analgesia and antinociceptive tolerance. As such, the changes in KOR expression in different regions of the nervous system in morphine tolerant rats were examined. We were able to attain morphine tolerance in rats via subcutaneous injection of morphine (10 mg/kg) twice daily for 7-consecutive days. Competitive real-time PCR, immunohistochemistry, and Western blot analyses were used to assess KOR expression in related regions of the nervous system, including the thalamus, hypothalamus, hippocampus, locus ceruleus (LC), periaqueductal gray (PAG), lumber-sacral spinal cord, and dorsal root ganglia (DRG). The expression of KOR increased in the locus ceruleus and spinal cord, but was significantly decreased in the DRG of morphine tolerant rats (P<0.05). No other significant changes in KOR expression were observed in the other regions. Consequently, we propose that the locus ceruleus and spinal cord are likely the dominant CNS regions and the DRG is the main peripheral site in which chronic morphine exerts its effect on KOR. Prolonged morphine administration induces inconsistent changes of KOR in the central and peripheral nervous system.
Li
Xuan-ying
XY
Department of Pain Medicine, Xuan Wu Hospital, Capital Medical University, Beijing, China.
Sun
Li
L
He
Jie
J
Chen
Zhao-li
ZL
Zhou
Fang
F
Liu
Xiao-yan
XY
Liu
Ruo-shan
RS
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance / Q000502:physiology*; D005727:Ganglia, Spinal / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D008125:Locus Coeruleus / Q000378:metabolism*; D009020:Morphine / Q000008:administration & dosage; D009294:Narcotics / Q000008:administration & dosage; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D012333:RNA, Messenger; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D011957:Receptors, Opioid / Q000235:genetics / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*; D000094942:Nociceptin Receptor
D009020:Morphine; D009294:Narcotics; D012333:RNA, Messenger; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D000094942:Nociceptin Receptor; C000722285:Oprl1 protein, rat