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Papers of the Week


Papers: 9 Nov 2024 - 15 Nov 2024


2024 Nov 11


Nat Immunol


39528810

Editor's Pick

Immune drivers of pain resolution and protection.

Authors

Hakim S, Jain A, Woolf CJ

Abstract

Immune cells are involved in the pathogenesis of pain by directly activating or sensitizing nociceptor sensory neurons. However, because the immune system also has the capacity to self-regulate through anti-inflammatory mechanisms that drive the resolution of inflammation, it might promote pain resolution and prevention. Here, we describe how immune cell-derived cytokines can act directly on sensory neurons to inhibit pain hypersensitivity and how immune-derived endogenous opioids promote analgesia. We also discuss how immune cells support healthy tissue innervation by clearing debris after nerve injury, protecting against axon retraction from target tissues and enhancing regeneration, preventing the development of chronic neuropathic pain. Finally, we review the accumulating evidence that manipulating immune activity positively alters somatosensation, albeit with currently unclear molecular and cellular mechanisms. Exploration of immune-mediated analgesia and pain prevention could, therefore, be important for the development of novel immune therapies for the treatment of clinical pain states.