03/04/2024
Hot off the press 🔥
Neuroinflammation in osteoarthritis. From pain to mood disorders
👉 Osteoarthritis (OA) is the most frequent form of musculoskeletal disease and affects millions of people in the world, especially the elderly. Thus, considering the increase in life expectancy, the number of subjects suffering from this pathology is growing every year. (https://ard.bmj.com/content/73/7/1323, https://www.sciencedirect.com/science/article/pii/S1521694214000059?via%3Dihub)
👉As pain intensity in OA shows no direct correlation has to structural joint damage (https://bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/1471-2474-12-144), various authors suggest the existence of a neuropathic or nociplastic component (https://link.springer.com/article/10.1007/s11926-012-0279-x, https://www.nature.com/articles/nrrheum.2014.47, https://pubmed.ncbi.nlm.nih.gov/38524267/)-
📘 In a recent review paper, Amodeo et al. (https://pubmed.ncbi.nlm.nih.gov/38556026/) describe the role of neuroinflammation in osteoarthritic pain and its interaction with mood disorders: Several studies have shown that, following injury or infections, the nervous system exhibits the typical features of inflammation, named neuroinflammation (https://www.mdpi.com/1420-3049/27/10/3194), a localized form of inflammation that occurs in PNS (nerves and ganglia) and CNS (spinal cord and brain, https://pubs.asahq.org/anesthesiology/article/129/2/343/18003/Neuroinflammation-and-Central-Sensitization-in).
💡 Numerous factors, such as trauma or the normal aging process, contribute to neuroinflammation. It is also a major cause and the driver of the progression of several neurodegenerative and neuropsychiatric diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and depression (https://onlinelibrary.wiley.com/doi/10.1111/ejn.14720, https://www.mdpi.com/1422-0067/23/11/5938). In addition, neuroinflammation is associated with different types of pain involving the CNS, such as central neuropathic pain, but also quite unexpectedly with other pain conditions, such as OA pain.
👉Indeed, it is now clear that some painful conditions for a long time considered as being exquisitely peripheral (e.g., OA pain or chronic constriction injury of the sciatic nerve) also manifest typical features of centrally driven pain, including signs of neuroinflammation in the PNS and CNS. (https://pubmed.ncbi.nlm.nih.gov/38556026/))
👉 Primary afferent fibers innervating the joint project to several spinal cord segments and terminate in both the superficial and deeper laminae, where they make synapse with second-order dorsal horn neurons (https://pubmed.ncbi.nlm.nih.gov/17678850/), which become hyperexcitable following pathological changes in the joint, with a reduction of their firing threshold and an enhancement of their responses to joint stimulation (https://pubmed.ncbi.nlm.nih.gov/38556026/). Furthermore, sensitized dorsal horn neurons expand their receptive fields, a mechanism that underlies the spread of hypersensitivity from the knee joint to adjacent areas (https://www.nature.com/articles/s41598-018-25581-8). Thus, neuroinflammation in the spinal cord is a distinctive sign of persistent pain (https://journals.lww.com/anesthesia-analgesia/fulltext/2019/04000/microglial_modulation_as_a_target_for_chronic.19.aspx).
👉 Continuous nociceptive inputs from the joint by significantly elevated proinflammatory cytokines such as IL-1ß, IL-6 and TNF alpha driven by activated Schwann cells, satellite glial cells (SGCs) and infiltrating macrophages express specific markers, and release pro-inflammatory cytokines, thus contributing to the generation and maintenance of an inflammatory environment. affect the activation of non-neuronal cells, primarily microglia and less consistent astrocytes in the spinal cord and brain.
🧠 Neuroinflammation is further characterized by vascular changes resulting in increased blood–brain barrier (BBB) permeability, which leads to increased invasion of leukocytes, activation of glial cells, and eventually production of inflammatory mediators, including cytokines and chemokines (https://pubs.asahq.org/anesthesiology/article/129/2/343/18003/Neuroinflammation-and-Central-Sensitization-in).
🤔 The authors therefore hypothesize that an efficacious control of the neuroinflammatory components during OA (i.e. by new drugs like microglia inhibitors) and/or transdiagnostic interventions like exercise therapy, https://www.sciencedirect.com/science/article/pii/S0361923016300557 may represent a promising strategy to counteract both pain and related comorbidities.
