Chemical mediation and involvement of the glial cell in the morphine-induced antinociception in the nulliparous and primiparous rats submitted to nerve ligation

Abstract

In female rats, the reproductive experience triggers permanent neural changes mainly as a result of hormonal and neurochemical actions. Among the neural changes observed in response to hormonal and neurochemical changes of reproductive experience, stands out the adjustment operation of the endogenous opioid system, evidenced mainly by the different responses of nulliparous and primiparous rats to morphine in relation to maternal behavior. However, it still has not been demonstrated if the characteristics of maternal behavior observed between virgins/nulliparous and primiparous rats are also reflected with respect to morphine-antinociceptive response. Considering that the neuropathies are chronic painful conditions that affect a large portion of the female population, causing great socio-economic impact, this study aims to assess the existence of differences in the morphine-antinociceptive response between nulliparous and primiparous rats subjected to ligature of the sciatic nerve model. In this sense, the present study aims to evaluate if the spinal and/or supraspinal chemical mediation and participation of glial cells in the antinociceptive effect of morphine behave distinctly between neuropathic nulliparous and primiparous rats. To test this hypothesis, the present study will assess the effects of dorsolateral funiculus lesion or intraperitoneal and/or intrathecal injection of the adrenergic, serotonergic, cholinergic, GABAergic and cholecystokininergic antagonists on morphine-induced antinociception in neuropathic nulliparous and primiparous rats in mechanical nociception test. Furthermore, the study will evaluate if the antinociception of morphine in neuropathic nulliparous and primiparous rats involves inhibition of the spinal glial activity during the time course of pain induced by nerve injury. Thus, expression of CD11b and GFAP membrane protein that are, respectively, markers of activated microglia and astrocytes, will be measured in spinal cord tissue by Western Blot. The results of this study will allow us to better understand the mechanisms of the morphine-antinociceptive action in nulliparous and primiparous rats in pathological pain conditions.