Involvement of spinal microglial P2X7 receptor in generation of tolerance to morphine analgesia in rats.
Morphine loses analgesic potency after repeated administration. The underlying mechanism is not fully understood. Glia are thought to be involved in morphine tolerance, and P2X(7) purinergic receptor (P2X(7)R) has been implicated in neuron-glia communication and chronic pain. The present study demonstrated that P2X(7)R immunoreactivity was colocalized with the microglial marker OX42, but not the astrocytic marker GFAP, in the spinal cord. The protein level of spinal P2X(7)R was upregulated after chronic exposure to morphine. Intrathecal administration of Brilliant Blue G (BBG), a selective P2X(7)R inhibitor, significantly attenuated the loss of morphine analgesic potency, P2X(7)R upregulation, and microglial activation. Furthermore, RNA interference targeting the spinal P2X(7)R exhibited a similar tolerance-attenuating effect. Once morphine analgesic tolerance is established, it was no longer affected by intrathecal BBG. Together, our results suggest that spinal P2X(7)R is involved in the induction but not maintenance of morphine tolerance.
Unit of Pain Research, Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200032, China.
Dong
D
Zhou
Meng-Ling
ML
Chen
Yu-Qiu
YQ
Zhang
Zhi-Qi
ZQ
Zhao
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D039481:CD11b Antigen / Q000378:metabolism; D004361:Drug Tolerance; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D058919:Purinergic P2 Receptor Antagonists; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7; D012394:Rosaniline Dyes / Q000008:administration & dosage / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation
D000701:Analgesics, Opioid; D039481:CD11b Antigen; D058919:Purinergic P2 Receptor Antagonists; D034741:RNA, Small Interfering; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D012394:Rosaniline Dyes; D009020:Morphine; C004692:coomassie Brilliant Blue