Key points are not available for this paper at this time.
• Pain is a neuro-immune condition in which immune cells play a role in initiation, sensitization and resolution mechanisms. • Innate and adaptive immune cells contribute to pain modulation through both pro-inflammatory and anti-inflammatory pathways. • The neuro-immune axis represents a promising therapeutic target for pain relief. Background: Pain is a neuro-immune condition in which immune cells interact with the somatosensory system, contributing not only in the initiation and sensitization of pain but also in its resolution. This review aims to decipher the immunological pathways implicated in pain, illustrating how immune cells and mediators contribute to pain persistance and examining new therapeutic prospects. Findings: Innate and adaptive immune cells such as macrophages, T and B cells, neutrophils, mast cells, and NK cells contribute to pain modulation through both pro-inflammatory and anti-inflammatory pathways. Peripheral and central sensitization as well as the recent concept of immunoception highlight the major role of neuro-immune interactions in pain perception. Therapeutic strategies targeting the immune system including cytokine inhibitors, low-dose IL-2, Janus kinase inhibitors, or emerging strategies such as vagus nerve stimulation, gut microbiota modulation, and specialized pro-resolving mediators might be of interest in pain resolution. Conclusions: Pain modulation involves complex neuro-immune interactions, with immune cells playing dual roles as both triggers and regulators of pain. A deeper understanding of these mechanisms opens new therapeutic avenues, emphasizing the potential of targeting immune pathways to prevent and manage chronic pain, particularly in rheumatic disorders.
Paolini et al. (Sat,) studied this question.