Opioid drugs are unmatched in their efficacy in managing pain. However, their clinical use is severely constrained by serious side effects: individuals can develop tolerance (requiring ever-higher doses), physical dependence, constipation, opioid-use disorder and life-threatening respiratory depression. To treat pain more safely, substantial efforts have been made to modify the chemical structures of opioids and discover druggable targets. However, pain management has only slightly improved in the past few decades, and great challenges remain in easing the suffering caused by chronic pain. Writing in Nature, Oswell et al.1 investigate alternative paths to alleviate the negative emotional experience of pain while keeping sensory processing intact.
doi: https://doi.org/10.1038/d41586-025-03987-5
References Oswell, C. S. et al. Nature https://doi.org/10.1038/s41586-025-09908-w (2026). Grahek, N. Feeling Pain and Being in Pain 1st edn (BIS Publishers, 2001). Armbruster, B. N., Li, X., Pausch, M. H., Herlitze, S. & Roth, B. L. Proc. Natl. Acad. Sci. USA 104, 5163–5168 (2007). Thomas, B. et al. Tremor Other Hyperkinet. Move. 15, 18 (2025). Cuschieri, A., Borg, N. & Zammit, C. Clin. Neurol. Neurosurg. 223, 107516 (2022). Download references
Competing Interests The authors declare no competing interests.
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