Pain-resolving immune mechanisms in neuropathic pain

Interactions between the immune and nervous systems are of central importance in neuropathic pain, a common and debilitating form of chronic pain caused by a lesion or disease affecting the somatosensory system. Our understanding of neuroimmune interactions in pain research has advanced considerably. Initially considered as passive bystanders, then as culprits in the pathogenesis of neuropathic pain, immune responses in the nervous system are now established to underpin not only the initiation and progression of pain but also its resolution. Indeed, immune cells and their mediators are well-established promoters of neuroinflammation at each level of the neural pain pathway that contributes to pain hypersensitivity. However, emerging evidence indicates that specific subtypes of immune cells (including antinociceptive macrophages, pain-resolving microglia and T regulatory cells) as well as immunoresolvent molecules and modulators of the gut microbiota-immune system axis can reduce the pain experience and contribute to the resolution of neuropathic pain. This Review provides an overview of the immune mechanisms responsible for the resolution of neuropathic pain, including those involved in innate, adaptive and meningeal immunity as well as interactions with the gut microbiome. Specialized pro-resolving mediators and therapeutic approaches that target these neuroimmune mechanisms are also discussed. Chronic neuropathic pain is a leading cause of disability that remains therapeutically challenging. Here, Fiore et al. review the immune mechanisms that contribute to the resolution of chronic neuropathic pain. Contributions of the gut microbiome and specialized pro-resolving mediators are also discussed, along with potential therapeutic strategies.

Automated summary

Interactions between the immune and nervous systems play a central role in neuropathic pain. Immune cells and their mediators contribute to neuroinflammation and pain hypersensitivity, but recent evidence shows that certain immune cells and molecules can help resolve neuropathic pain. This review provides an overview of the immune mechanisms and therapeutic approaches for the resolution of neuropathic pain, including interactions with the gut microbiome.