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Opioids, the wonderful analgesics, remain the mainstay in the clinical management of moderate to severe pain. However, development of analgesic tolerance and increase in pain sensitivity are some of the major concerns following opioid treatment. Studies suggest that NMDA receptor-mediated intracellular events play a role in mediating these effects. Moreover, NMDA receptor antagonists effectively prevent and gradually reverse opioid analgesic tolerance. Collectively, these studies unfold the involvement of NMDA receptor in opioid tolerance.
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