N-acetylcysteine prevents ethanol-induced neuropathic pain by downregulating nociceptive activation of supraspinal brain areas.

Considering the important clinical applications of N-acetylcysteine (NAC), the present study investigated the effects of NAC treatment on ethanol-induced neuropathic alterations. For this purpose, a total number of eighty-one male adult Wistar rats were used. Alcoholic neuropathy was induced by administration of 38 % (v/v) ethanol (10 g/kg/day, oral gavage) for 10 weeks. NAC solution (1.4 g/kg/day, oral gavage) was administered immediately after ethanol treatment, also for 10 weeks. The electronic von Frey, Randall Selitto and tail flick tests were used to characterize the nociceptive thresholds to mechanical and thermal stimulations. The Rota-rod test was used to evaluate motor coordination, whereas the open field test was employed to assess general locomotor activity. The present study also determined the integrity of the sciatic nerve and the number of c-Fos immunoreactive neurons in key brain structures. As expected, long-term exposure to ethanol reduced the thickness of myelin sheath in the peripheral nerve, as well as induced allodynia, mechanical and thermal hypernociception, as well as motor incoordination. Although ethanol treatment did not alter general locomotor activity, it increased the number of rearing events, indicating enhanced exploratory behavior. In the brain, chronic ethanol consumption was associated with higher levels of c-Fos expression in the dorsal raphe nucleus, parvocellular and magnocellular groups of the hypothalamic paraventricular nucleus, and also in the periaqueductal gray. Consistent with its protective effects, NAC treatment prevented the development of all ethanol-induced alterations, including at central level. Taken together, these results suggest that NAC consistently prevents ethanol-induced neuropathy.