Opioids: keeping the good, eliminating the bad


Two new studies show that mechanisms mediating the opioid side effects of tolerance, hyperalgesia and physical dependence are mediated spinally and can be dissociated from analgesia. These side effects can be selectively targeted by clinically available drugs without affecting their pain-relieving effects.

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Figure 1: Spinal and peripheral mediation of opioid side effects.

Marina Corral Spence/Springer Nature


  1. 1

    Volkow, N.D. & McLellan, A.T. N. Engl. J. Med. 374, 1253–1263 (2016).

    CAS  Article  Google Scholar 

  2. 2

    Wang, Y. et al. Nat. Med. 18, 385–387 (2012).

    Article  Google Scholar 

  3. 3

    Gutstein, H.B. & Trujillo, K.A. Brain Res. 626, 332–334 (1993).

    CAS  Article  Google Scholar 

  4. 4

    Burma, N.E.B. et al. Nat. Med. http://dx.doi.org/10.1038/nm.4281 (2017).

  5. 5

    Corder, G. et al. Nat. Med. http://dx.doi.org/10.1038/nm.4262 (2017).

  6. 6

    Wise, R.A. & Koob, G.F. Neuropsychopharmacology 39, 254–262 (2014).

    Article  Google Scholar 

  7. 7

    Lee, M., Silverman, S.M., Hansen, H., Patel, V.B. & Manchikanti, L. Pain Physician 14, 145–161 (2011).

    Google Scholar 

  8. 8

    Cahill, C.M., Walwyn, W., Taylor, A.M., Pradhan, A.A. & Evans, C.J. Trends Pharmacol. Sci. 37, 963–976 (2016).

    CAS  Article  Google Scholar 

  9. 9

    Roeckel, L.A., Le Coz, G.M., Gavériaux-Ruff, C. & Simonin, F. Neuroscience 338, 160–182 (2016).

    CAS  Article  Google Scholar 

  10. 10

    Drdla, R., Gassner, M., Gingl, E. & Sandkühler, J. Science 325, 207–210 (2009).

    CAS  Article  Google Scholar 

  11. 11

    Zhou, H.Y., Chen, S.R., Chen, H. & Pan, H.L. J. Neurosci. 30, 4460–4466 (2010).

    CAS  Article  Google Scholar 

  12. 12

    Kim, D.H., Fields, H.L. & Barbaro, N.M. Brain Res. 516, 37–40 (1990).

    CAS  Article  Google Scholar 

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Correspondence to Howard B Gutstein.

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Puig, S., Gutstein, H. Opioids: keeping the good, eliminating the bad. Nat Med 23, 272–273 (2017). https://doi.org/10.1038/nm.4277

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