Search Results (4)

Chronic pain is increasingly regarded as a condition of glia–neuronal dysregulation driven by persistent neuroinflammatory signaling. Following injury to nerves or tissues, glial cells, including astrocytes or satellite glial cells, undergo changes in their phenotype, thereby amplifying painful stimuli mediated by cytokines, chemokines, or ATP signaling. In response to injuries, activated microglia release several mediators such as BDNF, IL-1β, or TNF-α, thereby disrupting chloride homeostasis and inducing disinhibition in the dorsal horn, and sustaining maladaptive neuroimmune activity. Dysfunction of astrocytes, characterized by impaired glutamate clearance via excitatory amino acid transporter 2 and elevated C-X-C motif chemokine ligand 1 (CXCL1) and ATP release, drives neuronal sensitization, loss of neuroprotective metabolic support, and persistence of pain. In peripheral ganglia, connexin–43–mediated satellite glial cell coupling leads to hyperexcitability, resulting in neuropathic and orofacial pain and contributing to peripheral neuroinflammation. Presently, there is no unified framework for glial cell types, and the molecular mechanisms underlying microglial, astrocyte, and satellite glial cell contributions to the transition to chronic pain from acute pain are not completely elucidated. This review synthesizes current evidence on cellular and molecular mechanisms linking glial reactivity to pain chronification through sustained neuroinflammatory remodeling and impaired neuroprotection. It evaluates therapeutic strategies, including purinergic receptor P2X4 and toll-like receptor 4 antagonists, to metabolic reprogramming, exosome therapy, and neuromodulation, aimed at restoring homeostatic glial function and re-establishing neuroprotective glia–neuron interactions. A deeper understanding of the temporal and spatial dynamics of glial activation may enable personalized, non-opioid interventions that not only achieve durable analgesia but also prevent progressive neuroinflammatory damage and support long-term functional recovery. Full article

Despite the widespread use of experimental acute pain models, little exploration has been undertaken on the acute pain proteome in humans. We resolved to explore molecular alterations evoked by hypertonic saline (HS)-induced acute muscle pain and to map the spread of mechanical hyperalgesia. This study used a two-cohort design in healthy participants. Cohort one (n = 16) underwent intermittent blood sampling prior to, during, and following intramuscular HS (5%) infusion to allow for the discovery of the proteomic and cytokine profile of acute muscle pain. Cohort two (n = 10) underwent bilateral sensory testing during HS infusion, to map the spread of mechanical hyperalgesia. Molecular analysis in cohort one revealed a broad array of proteins and cytokines showing altered expression in response to acute muscle pain. Particularly, these alterations were linked to metabolism and immune response pathways suggestive of systemic effects of acute pain. Cohort two revealed a significant mechanical hyperalgesia which emerged in a distributed pattern over the ipsilateral limb to HS infusion. However, despite systemic molecular alterations, no such mechanical hyperalgesia was observed in the contralateral limb. This study demonstrates systemic molecular alterations resultant from acute HS-induced muscle pain, accompanied by spatially constrained sensory interactions. This dissociation implies that, at least in acute sensitization, widespread molecular changes may not necessarily translate into a correspondingly widespread sensory phenotype. Full article

Background Chronic low-back pain (LBP) is the largest contributor to disability worldwide, yet many assessments still reduce a complex, spatially distributed condition to a single 0–10 score. Body-map drawings capture location and extent of pain, but manual digitization is too slow and inconsistent for large studies or real-time telehealth. Methods Paper pain drawings from 332 adults in the multicenter COMEBACK study (four University of California sites, March 2021–June 2023) were scanned to PDFs. A Python pipeline automatically (i) rasterized PDF pages with pdf2image v1.17.0; (ii) resized each scan and delineated anterior/posterior regions of interest; (iii) registered patient silhouettes to a canonical high-resolution template using ORB key-points, Brute-Force Hamming matching, RANSAC inlier selection, and 3 × 3 projective homography implemented in OpenCV; (iv) removed template outlines via adaptive Gaussian thresholding, Canny edge detection, and 3 × 3 dilation, leaving only patient-drawn strokes; (v) produced binary masks for pain, numbness, and pins-and-needles, then stacked these across subjects to create pixel-frequency matrices; and (vi) normalized matrices with min–max scaling and rendered heat maps. RGB composites assigned distinct channels to each sensation, enabling intuitive visualization of overlapping symptom distributions and for future data analyses. Results Cohort-level maps replicated classic low-back pain hotspots over lumbar paraspinals, gluteal fold, and posterior thighs, while exposing less-recognized clusters along the lateral hip and lower abdomen. Neuropathic-leaning drawings displayed broader leg involvement than purely nociceptive patterns. Conclusions Our automated workflow converts pen-on-paper pain drawings into machine-readable digitized images and heat maps at the population scale, laying practical groundwork for spatially informed, precision management of chronic LBP. Full article

Back pain is one of the leading causes of disability worldwide and is frequently caused by degeneration of the intervertebral discs. The discs’ development, homeostasis, and degeneration are driven by a complex series of biochemical and physical extracellular matrix cues produced by and transmitted to native cells. Thus, understanding the roles of different cues is essential for designing effective cellular and regenerative therapies. Omics technologies have helped identify many new matrix cues; however, comparatively few matrix molecules have thus far been incorporated into tissue engineered models. These include collagen type I and type II, laminins, glycosaminoglycans, and their biomimetic analogues. Modern biofabrication techniques, such as 3D bioprinting, are also enabling the spatial patterning of matrix molecules and growth factors to direct regional effects. These techniques should now be applied to biochemically, physically, and structurally relevant disc models incorporating disc and stem cells to investigate the drivers of healthy cell phenotype and differentiation. Such research will inform the development of efficacious regenerative therapies and improved clinical outcomes. Full article