Macrophages and glial cells: Innate immune drivers of inflammatory arthritic pain perception from peripheral joints to the central nervous system

Abstract

Millions of people suffer from arthritis worldwide, consistently struggling with daily activities due to debilitating pain evoked by this disease. Perhaps the most intensively investigated type of inflammatory arthritis is rheumatoid arthritis (RA), where, despite considerable advances in research and clinical management, gaps regarding the neuroimmune interactions that guide inflammation and chronic pain in this disease remain to be clarified. The pain and inflammation associated with arthritis are not isolated to the joints, and inflammatory mechanisms induced by different immune and glial cells in other tissues may affect the development of chronic pain that results from the disease. This review aims to provide an overview of the state-of-the-art research on the roles that innate immune, and glial cells play in the onset and maintenance of arthritis-associated pain, reviewing nociceptive pathways from the joint through the dorsal root ganglion, spinal circuits, and different structures in the brain. We will focus on the cellular mechanisms related to neuroinflammation and pain, and treatments targeting these mechanisms from the periphery and the CNS. A comprehensive understanding of the role these cells play in peripheral inflammation and initiation of pain and the central pathways in the spinal cord and brain will facilitate identifying new targets and pathways to aide in developing therapeutic strategies to treat joint pain associated with RA.

The implications of Brain-derived neurotrophic factor in the biological activities of platelet-rich plasma.

“…Perhaps one of the most crucial cellular interactions for tissue repair where platelets play a pivotal role is the crosstalk with macrophages [52][53][54]. Macrophages are versatile cells and have an essential role in maintaining joint tissue homeostasis [55][56][57]. Beyond signaling molecules capable of initiating and drive a local inflammatory process such as IL-8, CCL2, and epinephrine, platelets may release other molecules that act on macrophage polarization and thus interfere with the dynamic plasticity of these cells, triggering the M1 (IL-1β, TNFα) or M2 phenotype (TGF-β, Fibrinogen) of macrophages present at the injured site [52,58,59].…”

“…In addition, this sensitization of joint nociceptors is also driven by inflammatory products that could be present on synovial fluid such as IL-1β, TNF-α, IL-6 and NGF [55,82,90].…”

Fibromyalgia and centralized pain in the rheumatoid arthritis patient

“…The role of the macrophage phenotype in the synovium and dorsal root ganglion, and glial cells in the CNS is still being elucidated, but given the data is suggested to be a key player in the onset and maintenance of arthritis-associated pain [44]. Photoacoustic imaging, based on the use of laser-generated United States, is currently being studied to detect the oxygenation status of tissue in patients with RA [45].…”

Potential mechanisms of exercise for relieving inflammatory pain: a literature review of animal studies

“…IP is a major health problem globally, affecting 350 million people worldwide, and its prevalence is increasing ( Malange et al, 2022 ). This increasing prevalence is associated with a lack of effective treatments.…”