Biology subjects

Hunt, M. A.

Publications and source records attributed to Hunt, M. A..

6 recordsLinked to original sources

bioRxiv2026

Tissue-to-Analysis Framework Enables Multiscale Mapping of the Architectural and Cellular Organization in the Human Dorsal Root Ganglion

Transcriptomic studies have helped us understand the dorsal root ganglias cellular milieu, yet our knowledge of protein expression and spatial organization/architecture remains less defined. Here we establish a comprehensive resource from processing through analysis of hDRG tissue. We optimize tissue-handling strategies and evaluate 114 antibodies targeting neuronal and non-neuronal cell types, identifying protocols that preserve neuronal morphology and antigen retain specificity. Integrating these workflows with our Deep Learning-assisted image analysis pipelines, we quantify size, expression, and spatial organization across 35,721 neurons from 15 donors. Female donors exhibited significantly larger neuronal somata, indicating sexual dimorphism. Neuronal subpopulations display clear spatial clustering. We further characterized the perineuronal niche, marked by dense vascularization, nuclear remodeling in perineuronal cells, and age-related increased turnover of neuron-associated macrophages. Together, this resource provides standardized methodologies and quantitative frameworks for reproducible protein-level interrogation of human sensory biology and pain mechanisms.

neuroscience↗

bioRxiv2025

Neutrophil-neuronal crosstalk drives arthritis-induced pain

Pain in rheumatoid arthritis (RA) often persists despite effective control of inflammation, suggesting distinct mechanisms driving nociception. In both patients and animal models, pain severity does not strongly correlate with the degree of inflammation1,2. Sensory neurons, with cell bodies located in the dorsal root ganglia (DRG), innervate peripheral tissues, including joints, and transmit pain signals to the central nervous system. Crosstalk between sensory neurons and immune cells occurs at all of these sites. While sensory neurons can be directly activated by immune mediators, it remains unclear whether pain-like behaviour in antibody-induced arthritis models arises independently of immune cell activity, or which immune cell populations and mediators are required to activate pronociceptive mechanisms. Through temporal profiling of the CAIA joint-DRG transcriptomic axis, we identified SEMA4D and OSM signalling as candidate molecular mediators of neutrophil-neuron communication and neuronal sprouting. The joint-DRG atlas also revealed persistent changes in the fibroblast-immune cellular composition of the joint, along with molecular changes in DRG neurons. We showed that mechanical and cold hypersensitivity, as well as sprouting of CGRP+ nociceptive fibers in synovial tissue of mice with collagen antibody-induced arthritis (CAIA), require neutrophils but not macrophages. Analysis of publicly available datasets showed that neutrophils from the synovium of RA patients express high levels of SEMA4D and OSM, and corresponding expression of their receptors, PLEXINB1 and OSMR, in human DRG neurons, underscoring the translational relevance of this axis. Both murine and human-derived DRG neurons sprout in response to OSM. Our findings demonstrate that neutrophils produce molecules that act as cues for nociceptor sensitization and structural remodelling. Targeting these molecules could improve the efficacy of RA treatments by reducing pain while simultaneously preventing disease progression.

immunology↗

bioRxiv2024

Microbially produced bile acids are associated with high levels of IgG autoantibodies and worse mental wellbeingin fibromyalgia subjects

Fibromyalgia (FM) is a disease primarily associated with chronic widespread pain, but other common symptoms are anxiety and depression. We previously proposed that autoimmunity contributes to FM based on findings of increased immunoglobulin G binding to satellite glial cells (anti-SGC IgG) in FM subjects compared to healthy controls (HC). Emerging research suggests that an altered gut microbiota composition is connected to psychological symptoms in FM rather than pain. Gut microbiota can produce or alter bile acids (BAs) and short-chain fatty acids (SCFAs), which have immune and inflammatory functions. Here, we investigate alterations in BA and SCFA concentrations in FM subjects compared to healthy controls (HC) and potential associations with FM symptoms and anti-SGC IgG levels. Bile acids and SCFAs were quantified using liquid chromatography coupled with high-resolution mass spectrometry and anti-SGC IgG levels were assessed with immunocytochemistry. The correlations between FM symptoms, anti-SGC IgG levels, and serum concentrations of 24 BAs and 11 SCFAs in 35 FM subjects and 32 matched HC were examined. Fibromyalgia subjects had significantly higher levels of microbially produced BAs than HC. Strikingly, 11 out of 24 BAs were significantly elevated in FM subjects with high, compared to those with low, anti-SGC IgG levels. Concentrations of specific BAs were associated with increased disease severity and worse mental well-being. These results revealed increased levels of secondary BAs in FM subjects compared to HC. The strong association between BAs, anti-SGC IgG levels, and mental well-being may help elucidate the importance of BAs in the psychological symptoms of FM. Significance statementFibromyalgia (FM) is a chronic pain syndrome that significantly impacts an individuals quality of life. In addition to persistent pain, people with FM often experience depression, anxiety, and irritable bowel syndrome. Previously, we identified autoantibodies that bind to satellite glial cells in the dorsal root ganglia associated with more severe FM symptoms. Our current results demonstrate a novel association between these autoantibodies in FM and bile acids (BAs). Bile acids are essential for lipid metabolism but also act as signaling molecules. We show that patients with elevated levels of autoantibodies also exhibit increased levels of BAs. Furthermore, the BAs strongly correlate with worse FM symptom severity, particularly affecting mental well-being. Our study suggests that lowering BA levels could alleviate the psychological symptoms associated with FM.

neuroscience↗

bioRxiv2024

Fibromyalgia patients have altered lipid concentrations associated with disease symptom severity and anti-satellite glial cell IgG antibodies

Autoimmunity and immunoglobulin G (IgG) autoantibodies may contribute to pain in a subset of fibromyalgia (FM) patients. Previously, we saw that IgG from FM patients induces pain-like behavior in mice and binds to satellite glial cells (anti-SGC IgG). The anti-SGC IgG levels were also associated with more severe symptomatology. Lipid metabolism in FM subjects is altered with lysophosphatidylcholines (LPCs) acting as pain mediators. The relationship between autoantibodies, lipid metabolism, and FM symptomatology remains unclear. We analyzed serum lipidomics with liquid chromatography mass spectrometry, anti-SGC IgG levels, and clinical measures in 35 female FM subjects and 33 age- and body mass index-balanced healthy controls (HC). Fibromyalgia subjects with higher anti-SGC IgG levels experienced more intense pain than those with lower levels. Sixty-three lipids were significantly altered between FM subjects and HC or between FM subjects with severe (FM severe) and mild symptoms (FM mild). Compared to HC, FM subjects had lower concentrations of lipid species belonging to the classes LPC (n = 10), lysophosphatidylethanolamine (n = 7), phosphatidylcholine (n = 4), and triglyceride (n = 5), but higher concentrations of diglyceride (n = 3). Additionally, FM severe had higher LPC 19:0, 22:0, and 24:1 and lower sphingomyelin (n = 9) concentrations compared to FM mild. A positive association was seen for LPC 22:0 and 24:1 with pain intensity and anti-SGC IgG levels in FM subjects. Taken together, our results suggest an association between altered lipid metabolism and autoimmune mechanisms in FM. PerspectiveOur results suggest an association between the postulated autoimmunity in FM and lipids that can act as pain mediators.

neuroscience↗

bioRxiv2024

Moving in pain - A preliminary study evaluating the immediate effects of experimental knee pain on locomotor biomechanics.

Pain changes how we move, but it is often confounded by other factors due to disease or injury. Experimental pain offers an opportunity to isolate the independent affect of pain on movement. We used cutaneous electrical stimulation to induce experimental knee pain during locomotion to study the short-term motor adaptions to pain. While other models of experimental pain have been used in locomotion, they lack the ability to modulate pain in real-time. Twelve healthy adults completed the single data collection session where they experienced six pain intensity conditions (0.5, 1, 2, 3, 4, 5 out of 10) and two pain delivery modes (tonic and phasic). Electrodes were placed over the lateral infrapatellar fat pad and medial tibial condyle to deliver the 10 Hz pure sinusoid via a constant current electrical stimulator. Pain intensity was calibrated prior to each walking bout based on the target intensity and was recorded using an 11-point numerical rating scale. Knee joint angles and moments were recorded over the walking bouts and summarized in waveform and discrete outcomes to be compared with baseline walking. Knee joint angles changed during the swing phase of gait, with higher pain intensities resulting in greater knee flexion angles. Minimal changes in joint moments were observed but there was a consistent pattern of decreasing joint stiffness with increasing pain intensity. Habituation was limited across the 30-90 second walking bouts and the electrical current needed to deliver the target pain intensities showed a positive linear relationship. Experimental knee pain shows subtle biomechanical changes and favourable habituation patterns over short walking bouts. Further exploration of this model is needed in real-world walking conditions and over longer timeframes to quantify motor adaptations.

neuroscience↗

bioRxiv2022

Fibromyalgia patients with high levels of anti-satellite glia cell IgG antibodies present with more severe symptoms

ObjectiveTransferring fibromyalgia patient IgG to mice induces pain-like behaviour and fibromyalgia IgG binds mouse and human satellite glia cells (SGCs). These findings suggest that autoantibodies could be part of fibromyalgia pathology. However, it is unknown how frequently fibromyalgia patients have anti-SGC antibodies and how anti-SGC antibodies associate with disease severity. MethodsWe quantified serum or plasma anti-SGC IgG levels in two fibromyalgia cohorts from Sweden and Canada using an indirect immunofluorescence murine cell culture assay. Fibromyalgia serum IgG binding to human SGCs in human dorsal root ganglia tissue sections was assessed by immunofluorescence (n=14/group). ResultsIn the cell culture assay anti-SGC IgG levels were increased in both fibromyalgia cohorts compared to controls. Elevated anti-SGC IgG was associated with higher levels of self-reported pain in both cohorts, and higher fibromyalgia impact questionnaire scores and increased pressure sensitivity in the Swedish cohort. Anti-SGC IgG levels were not associated with fibromyalgia duration. Swedish FM patients were clustered into FM-severe and FM-mild groups and the FM-severe group had elevated anti-SGC IgG compared to the FM-mild and controls. Anti-SGC IgG levels detected in culture were positively correlated with increased binding to human SGCs. Moreover, the FM-severe group had elevated IgG binding to human SGCs compared to the FM-mild and control groups. ConclusionsA subset of fibromyalgia patients have elevated levels of anti-SGC antibodies, and the antibodies are associated with more severe fibromyalgia severity. Screening fibromyalgia patients for anti-SGC antibodies could provide a path to personalized treatment options that target autoantibodies and autoantibody production.

neuroscience↗