Pain
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Antidepressants that block the reuptake of noradrenaline and/or serotonin are among the first-line treatments for neuropathic pain, although the mechanisms underlying this analgesia remain unclear. The noradrenergic locus coeruleus is an essential element of both the ascending and descending pain modulator systems regulated by these antidepressants. Hence, we investigated the effect of analgesic antidepressants on locus coeruleus activity in Sprague-Dawley rats subjected to chronic constriction injury (CCI), a model of neuropathic pain. ⋯ Moreover, in all animals, these antidepressants reduced the inhibitory period and augmented the late response. We propose that N-methyl-d-aspartate and alpha-2-adrenoceptors are involved in the analgesic effect of antidepressants. Antidepressant-mediated changes were correlated with behavioral effects indicative of analgesia in healthy and neuropathic rats.