Regulatory mechanisms and therapeutic potential of microglial inhibitors in neuropathic pain and morphine tolerance

Abstract

Microglia are important cells involved in the regulation of neuropathic pain (NPP) and morphine tolerance. Information on their plasticity and polarity has been elucidated after determining their physiological structure, but there is still much to learn about the role of this type of cell in NPP and morphine tolerance. Microglia mediate multiple functions in health and disease by controlling damage in the central nervous system (CNS) and endogenous immune responses to disease. Microglial activation can result in altered opioid system activity, and NPP is characterized by resistance to morphine. Here we investigate the regulatory mechanisms of microglia and review the potential of microglial inhibitors for modulating NPP and morphine tolerance. Targeted inhibition of glial activation is a clinically promising approach to the treatment of NPP and the prevention of morphine tolerance. Finally, we suggest directions for future research on microglial inhibitors.

Microglial inflammation modulates opioid analgesic tolerance

“…As a result, opioid tolerance has also increased, exacerbating opioid overuse. Recent studies indicate that opioid‐mediated microglial activation and production of different proinflammatory molecules may contribute to opioid tolerance (Du et al, 2020; Han et al, 2014; Zhang et al, 2011; Y. Zhang et al, 2017). Therefore, the challenge is to maintain the pain‐relieving effect of opioids while minimizing microglial activation in an effort to mitigate opioid tolerance and hyperalgesia in patients (Figure 1).…”