A Pharmacological Rationale to Reduce the Incidence of Opioid Induced Tolerance and Hyperalgesia: A Review

Beside neurons, opioid receptors (OR) are also expressed on non-neuron cells, and their distribution is altered by chronic opioid treatment. The activation of non-neuronal cells in peripheral mast cells and spinal cord microglia and astroglia induced by chronic opioid treatment causes an up-regulation of membrane receptors and abnormal production of pro-inflammatory cytokines and chemokines. These events induce sensitization of peripheral and spinal neurons, morphine tolerance and hyperalgesia, OR opioid receptor, NK1 neurokinin 1, CGRP calcitonin gene-related peptide, TRPV1 transient receptor potential vanilloid receptor 1, and PAR2 protease-activated receptor