Morphine acts primarily on μ opioid receptors to deliver its potent
analgesic effects. For the treatment of acute pain, postoperative pain,
and moderate to severe chronic pain, it has been frequently utilised
in clinics. However, morphine’s clinical use is hampered by a number
of unavoidable side effects, including drug dependence and tolerance,
respiratory depression, nausea, vomiting, and drowsiness. According
to reports, a number of mechanisms, such as desensitisation and
internalisation of the opioid receptor, heterodimers of G protein-
coupled receptors, activation of the adenosine 3’, 5’-monophosphate
pathway and the Mitogen-Activated Protein Kinase (MAPK) pathway,
among others, contribute to the development of morphine tolerance.
However, the available treatments for morphine tolerance management
are still insufficient. Cytokines are produced by a wide variety of cells,
including immune cells, endothelial cells, and different stromal cells.
Considering the nature