Opponent Process in Opioid Tolerance: Focus on Opioid Induced Hyperalgesia

Despite opioids’ potent analgesic effectiveness, their use is limited by detrimental neuroadaptations. Opioid tolerance is associated with opioid induced hyperalgesia (OIH) since its prevention restores opioid analgesic effects. Many features of opioid-induced hyperalgesia can be viewed in terms of adaptive response intended to normalize net activity by engaging opposing or compensatory regulatory mechanisms or signaling pathways to reduce opioid responses. This phenomenon refers to the opponent process theory. In this session, Dr Rivat will describe opponent process and how opponent process contributes to the adaptation of the analgesic effects of opioid. Numerous cellular and molecular changes arising from primary sensory neurons of the DRG mediate neuronal hyperexcitability produced by chronic morphine. This supports the development of long-term potentiation (LTP) in the spinal cord which depends on pre-synaptic NMDARs shown by electrophysiological studies. Chronic opioids cause adaptive plasticity in peripheral nociceptors, which in turn alters activity of downstream nociceptive networks (spinal cord LTP), leading to OIH. Dr Rivat will highlight the role of the FLT3 (the Fms-LikeTyrosine kinase 3 receptor) receptor expressed in dorsal root ganglia in the development of OIH. He will present preclinical observations showing that the blockade of FLT3 receptor may increase morphine analgesic effect.