Modulation Effects Of Adrenomedullin And MrgC Receptors On The Function Of μ-opioid Receptors—The G Proteins Mechanism

Pain perception is protective mechanism warning a potential injury. However, pathological pain including inflammatory and neuropathic pain ruins people’s life. As opiates are most effective drugs to treat pain, repeated application of opiates produces morphine tolerance limiting their clinic use. Therefore, it is important to study the mechanisms of pain and opiate tolerance which could help to find novel therapeutics for pain.These results suggest:1. Increase in AM biological activity contributs to the development and maintainence of chronic morphine-associated hyperalgesia. Chronic morphine upregulates AM expression in the primary sensory neurons via activation of μ-opioid receptors and PKC signal transduction pathway.2. AM recruits nitric oxide and CGRP during CFA-induced inflammation. AM-NO-CGRP is a cascade contributing to the induction of chronic hyperalgesia in CFA-induced inflammation.3. Persistent activity of AM in the spinal dorsal horn can be ascribed to the development of morphine tolerance and associated hyperalgesia. The functional alterations of μ-opioid receptor-coupled G proteins may be a novel mechanism underlying AM’s contributions to morphine tolerance.4. Activation of Mrg receptors can modulate μ-opioid receptor-coupled G proteins in the spinal dorsal horn increasing the potency of morphine-induced analgesia.This study is aimed to investigate the role of AM in morphine tolerance and inflammatory pain, and the modulation effects of AM and MrgC receptors on the function of μ-opioid receptors. The results in the present study added some novel data which may help to understand the mechanisms of inflammatory pain and morphine tolerance.