Morphine-induced Neurochemical Alterations In Rat DRG Neurons

Up to now, opiates are still the most effective analgesics to treat moderate to severe pain. However, long term exposure to morphine can cause tolerance seriously limiting their use in clinic. Morphine tolerance could affect pain therapy seriously. It has been documented that chronic morphine can induced upregulation of AM, CGRP and IL-1βexpressions contributing to the development of morphine tolerance. The present study aimed to investigate the effects of morphine treatment on mRNA expression of AM, CGRP and IL-1β. Their possible mechanisms were also explored.We observed that morphine treatment induced an increase in AM, CGRP and IL-1βmRNA. The first increase appeared at 10 min,30 min and 10 min following the exposure of cultured DRG to 3.3μM morphine. The similar treatment induced bi-phase alterations of MrgC mRNA:a decrease before day 3 followed by an increase. Furthermore, application of AM receptor antagonist AM22-52 inhibited the increase of AM, CGRP and IL-1 p mRNA. In addition, co-treatment of morphine with PKC inhibitor CLT attenuated the morphine-induced increase of AM mRNA.These results suggest that similar to large dose, administration of moderate dose of morphine also induced the increase in pronociceptive mediators AM, CGRP and IL-1β. Moreover, this increase occurred within a short period of time (10 min-1 hour) following the use of morphine. As increase of AM mRNA was before that of CGRP and IL-1βmRNA and treatment with AM receptor antagonist AM22-52, it is suggested that upregulation could be the upstream effector for CGRP and IL-1β. In addition, the activation of PKC signaling pathway is attributed to the morphine-induced AM mRNA increase. Morphine treatment induced bi-phase alterations of MrgC mRNA:decrease before 3 days followed by the increase. The significance of MrgC mRNA alterations in cultured DRG produced by the application of morphine is not clear yet in a moment.