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 demon...

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Bibliographic Details
Published in:	The Journal of neuroscience 2010-06, Vol.30 (23), p.8042-8047
Main Authors:	Zhou, Dong, Chen, Meng-Ling, Zhang, Yu-Qiu, Zhao, Zhi-Qi
Format:	Article
Language:	eng
Subjects:	Analgesics, Opioid - administration & dosage Analgesics, Opioid - pharmacology Animals Astrocytes - drug effects Astrocytes - metabolism Blotting, Western Brief Communications CD11b Antigen - metabolism Drug Tolerance Immunohistochemistry Injections, Subcutaneous Male Microglia - drug effects Microglia - metabolism Morphine - administration & dosage Morphine - pharmacology Purinergic P2 Receptor Antagonists Rats Rats, Sprague-Dawley Receptors, Purinergic P2 - genetics Receptors, Purinergic P2 - metabolism Receptors, Purinergic P2X7 RNA, Small Interfering Rosaniline Dyes - administration & dosage Rosaniline Dyes - pharmacology Spinal Cord - drug effects Spinal Cord - metabolism Up-Regulation
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Summary:	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.
ISSN:	0270-6474 1529-2401