Chronic use of opioid analgesics can cause analgesic tolerance and opioid-induced hyperalgesia (OIH), contributing to dose escalation in patients. Corder et al. here provide evidence that, in mice, these unwanted effects, and the underlying altered circuit plasticity, are mediated by μ opioid receptors (MORs) expressed by primary nociceptors. Targeted genetic deletion of peripheral MORs or treatment with peripherally restricted MOR antagonists suppressed opioid tolerance and OIH without affecting analgesia, suggesting a possible strategy to improve pain management in patients.
References
Corder, G. et al. Loss of μ opioid receptor signaling in nociceptors, but not microglia, abrogates morphine tolerance without disrupting analgesia. Nat. Med. http://dx.doi.org/10.1038/nm.4262 (2017)
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Whalley, K. Improving opioids. Nat Rev Neurosci 18, 130 (2017). https://doi.org/10.1038/nrn.2017.22
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DOI: https://doi.org/10.1038/nrn.2017.22