Human Studies

Murine models have demonstrated that the major histocompatibility complex (MHC) is associated with pain-like behavior in peripheral nerve injury, however, the same association has not been shown when considering injury to the central nervous system (CNS), which more closely mimics the damage to the CNS experienced by MS patients. Previous research has indicated the DQB103:02 allele of the class II HLA genes as being associated with development of neuropathic pain in persons undergoing inguinal hernia surgery or with lumbar spinal disk herniation. Whether this HLA allele plays a part in susceptibility to pain, has not, as far as we are aware, been previously investigated. This study utilizes information on DQB103:02 alleles as part of the EIMS, GEMS, and IMSE studies in Sweden. It also uses register data for 3,877 MS patients, and 4,548 matched comparators without MS, to assess whether the DQB103:02 allele is associated with prescribed pain medication use, and whether associations with this genotype differ depending on MS status. Our results showed no association between the DQB103:02 genotype and pain medication in MS patients, with an adjusted odds ratio (OR) of 1.02 (95% CI 0.85-1.24). In contrast, there was a statistically significant association of low magnitude in individuals without MS [adjusted OR 1.18 (95% CI 1.03-1.35)], which provides support for HLA influence on susceptibility to pain in the general population. Additionally, the effect of zygosity was evident for the non-MS cohort, but not among MS patients, suggesting the DQB103:02 allele effect is modified by the presence of MS.

Back pain is the leading cause of disability worldwide and is associated with obesity and chronic low-grade inflammation. Alterations in intestinal microbiota may contribute to the pathogenesis of back pain through metabolites affecting immune and inflammatory responses. We compared the gut microbiota composition in a cohort of 36 overweight or obese individuals with or without self-reported back pain in the preceding month. Participants were characterized for anthropometry; bone health; metabolic health; inflammation; dietary intake; and physical activity. Demographic, clinical, biochemical characteristics, diet and physical activity were similar between participants with ( = 14) or without ( = 22) back pain. Individuals with back pain had a higher abundance of the genera ( = 0.0008; FDR = 0.027) ( = 0.0098; FDR = 0.17), and ( = 0.02; FDR = 0.27) than those without back pain. abundance remained higher in individuals with back pain in the past 2 weeks, 6 months, and 1 year. was positively correlated with BMI (rho = 0.35, = 0.03), serum adipsin (rho = 0.33, = 0.047), and serum leptin (rho = 0.38, = 0.02). Our findings suggest that back pain is associated with altered gut microbiota composition, possibly through increased inflammation. Further studies delineating the underlying mechanisms may identify strategies for lowering abundance to treat back pain.

The diagnosis of trigeminal neuralgia (TN) is challenging due to the lack of objective diagnostics. Corneal confocal microscopy (CCM) is a non-invasive ophthalmic imaging technique, which allows quantification of corneal nerve fibers arising from the trigeminal ganglion and may allow the assessment of neurodegeneration in TN. CCM was undertaken in 11 patients with TN and 11 age-matched healthy controls. Corneal nerve fiber density (CNFD), corneal nerve branch density, corneal nerve fiber length (CNFL), corneal nerve fiber width, corneal nerve fiber area, and dendritic cell and non-dendritic cell density with or without nerve fiber contact were quantified. Patients with TN had significantly lower CNFD and CNFL but no difference for any other corneal nerve or dendritic cell parameter in the ipsilateral and the contralateral cornea compared to the control group. There was no significant difference in corneal nerve and cell parameters between patients with TN with and without involvement of the ophthalmic nerve (V1) or with nerve vessel conflict. Corneal confocal microscopy is a rapid non-invasive imaging technique that identifies symmetrical corneal nerve loss in patients with TN.

Previous studies found higher levels of pain severity and disability to be associated with higher costs and lower health-related quality of life. However, these findings were based on cross-sectional data and little is known about the longitudinal relationships between pain severity and disability versus health-related quality of life and costs among chronic low back pain patients. This study aims to cover this knowledge gap by exploring these longitudinal relationships in a consecutive cohort.

Chronic pain is common in people with Parkinson's disease, and is often considered to be caused by the motor impairments associated with the disease. Altered top-down processing of pain characterises several chronic pain conditions and occurs when the cortex modifies nociceptive processing in the brain and spinal cord. This contrasts with bottom-up modulation of pain whereby nociceptive processing is modified on its way up to the brain. Although several studies have demonstrated altered bottom-up pain processing in Parkinson's, the contribution of enhanced anticipation to pain and atypical top-down processing of pain has not been fully explored. During the anticipation to noxious stimuli, EEG source localisation reported an increased activation in the mid-cingulate cortex and supplementary motor area in the Parkinson's disease group compared to the healthy control group during Mid [-1500 -1000] and Late anticipation [-500 0], indicating enhanced cortical activity before noxious stimulation. The Parkinson's disease group was also more sensitive to the laser and required a lower voltage level to induce pain. This study provides evidence supporting the hypothesis that enhanced top-down processing of pain may contribute to the development of chronic pain in Parkinson's. Additional research to establish whether the altered anticipatory response is unique to noxious stimuli is required as no control stimulus was used within the current study. With further research to confirm these findings, our results inform a scientific rationale for novel treatment strategies of pain in Parkinson's disease, including mindfulness, cognitive therapies and other approaches targeted at improving top down processing of pain. This article is protected by copyright. All rights reserved.