Substance P-neurokinin 1 receptor signal involves the development of osteoarthritis-induced chronic pain in rats

Chronic pain is a major symptom of osteoarthritis (OA). Substance P (SP) plays a role in inflammation and nociception, but its role in OA pain chronicity remains unclear. This study investigates whether SP-neurokinin 1 (NK1R) signal mediates the development of chronic pain in monosodium iodoacetate (MIA)-induced OA model rats. GR 82334 (GR), an NK1R antagonist, was injected intra-articularly 30minutes before (pre-GR) or 1day after (post-GR) MIA injection to examine the effects of NK1R blocking of early inflammation on chronic pain and neuroimmune interactions in the knee joint, dorsal root ganglion (DRG), and spinal dorsal horn (SDH). GR reduced edema and knee bending scores; post-GR treatment more effectively prevented paw withdrawal threshold reduction than pre-GR treatment. Early NK1R blocking suppressed the expression of CGRP, SP, and pro-inflammatory factors (CCL2, TNFα, IL-1β, and IL-6), and M1 macrophage activation in the knee joints at 14days post-MIA. GR also reduced the expression of pro-inflammatory factors and M1 macrophage activation in the L3-5 DRGs and decreased the expression of CGRP, SP, and pro-inflammatory factors, and microglial activation in the L3-5 SDHs. These findings suggest that early SP-NK1R signal-mediated inflammation contributes to OA chronic pain progression via neuroimmune interactions.