Research progress of p38 as a new therapeutic target against morphine tolerance and the current status of therapy of morphine tolerance

With the development of the medical industry, new painkillers continue to appear in people's field of vision, but so far no painkiller can replace morphine. While morphine has a strong analgesic effect, it is also easy to produce pain sensitivity and tolerance. Due to the great inter-individual differences in patient responses, there are few clear instructions on how to optimise morphine administration regimens, which complicates clinicians' treatment strategies and limits the effectiveness of morphine in long-term pain therapy. P38MAPK is a key member of the MAPK family. Across recent years, it has been discovered that p38MAPK rises dramatically in a wide range of morphine tolerance animal models. Morphine tolerance can be reduced or reversed by inhibiting p38MAPK. However, the role and specific mechanism of p38MAPK are not clear. In this review, we synthesise the relevant findings, highlight the function and potential mechanism of p38MAPK in morphine tolerance, as well as the present status and efficacy of morphine tolerance therapy, and underline the future promise of p38MAPK targeted morphine tolerance treatment.