Morphine acts on spinal dynorphin neurons to cause itch through disinhibition

Eileen Nguyen1,2, Grace Lim3,4, Huiping Ding5, Junichi Hachisuka1,6, Mei-Chuan Ko5, Sarah E Ross7

  1. Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
  2. Medical Scientist Training Program, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
  3. Department of Anesthesiology and Perioperative Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
  4. Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA 15213, USA.
  5. Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
  6. Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, UK.
  7. Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. saross@pitt.edu.

Abstract

Morphine-induced itch is a very common and debilitating side effect that occurs in laboring women who receive epidural analgesia and in patients who receive spinal morphine for relief of perioperative pain. Although antihistamines are still widely prescribed for the treatment of morphine-induced itch, their use is controversial because the cellular basis for morphine-induced itch remains unclear. Here, we used animal models and show that neuraxial morphine causes itch through neurons and not mast cells. In particular, we found that spinal dynorphin (Pdyn) neurons are both necessary and sufficient for morphine-induced itch in mice. Agonism of the kappa-opioid receptor alleviated morphine-induced itch in mice and nonhuman primates. Thus, our findings not only reveal that morphine causes itch through a mechanism of disinhibition but also challenge the long-standing use of antihistamines, thereby informing the treatment of millions worldwide.

Presented By Eileen Nguyen

Medicine, NeuroscienceNicholas Liao2021-02 (Feb)