Antidepressant treatment of neuropathic pain: looking for the mechanism

Neuropathic pain arises as a direct consequence of a lesion or disease affecting the somatosensory system. Among the recommended first-line treatments are antidepressant drugs - that is, molecules that were initially developed to treat other disorders of the nervous system. While their clinical efficacy against neuropathic pain was established more than 30 years ago, there is little information on the mechanism underlying their antidepressant action. However, understanding the therapeutic mechanism of these treatments could help to improve them, or even lead to new therapeutic approaches. In this article, we discuss the difficulties in conducting relevant preclinical research on neuropathic pain treatment with antidepressant drugs and we present the most recent findings on the putative mechanism, which highlight the role of beta 2-adrenoceptors and delta-opioid receptors.