The Downregulation of Opioid Receptors and Neuropathic Pain

Neuropathic pain (NP) refers to pain caused by primary or secondary damage or dysfunction of the peripheral or central nervous system, which seriously affects the physical and mental health of 7-10% of the general population. The etiology and pathogenesis of NP are complex; as such, NP has been a hot topic in clinical medicine and basic research for a long time, with researchers aiming to find a cure by studying it. Opioids are the most commonly used painkillers in clinical practice but are regarded as third-line drugs for NP in various guidelines due to the low efficacy caused by the imbalance of opioid receptor internalization and their possible side effects. Therefore, this literature review aims to evaluate the role of the downregulation of opioid receptors in the development of NP from the perspective of dorsal root ganglion, spinal cord, and supraspinal regions. We also discuss the reasons for the poor efficacy of opioids, given the commonness of opioid tolerance caused by NP and/or repeated opioid treatments, an angle that has received little attention to date; in-depth understanding might provide a new method for the treatment of NP.