Human Studies

Sedentary lifestyle, chronic disease, or microgravity can cause muscle deconditioning that then has an impact on other physiological systems. An example is the nervous system, which is adversely affected by decreased physical activity resulting in increased incidence of neurological problems such as chronic pain. We sought to better understand how this might occur by conducting RNA sequencing experiments on muscle biopsies from human volunteers in a 5-week bed-rest study with an exercise intervention arm. We also used a computational method for examining ligand-receptor interactions between muscle and human dorsal root ganglion (DRG) neurons, the latter of which play a key role in nociception and are generators of signals responsible for chronic pain. We identified 1352 differentially expressed genes (DEGs) in bed rest subjects without an exercise intervention but only 132 DEGs in subjects with the intervention. Among 591 upregulated muscle genes in the no intervention arm, 26 of these were ligands that have receptors that are expressed by human DRG neurons. We detected a specific splice variant of one of these ligands, placental growth factor (PGF), in deconditioned muscle that binds to neuropilin 1, a receptor that is highly expressed in DRG neurons and known to promote neuropathic pain. We conclude that exercise intervention protects muscle from deconditioning transcriptomic changes, and prevents changes in the expression of ligands that might sensitize DRG neurons, or act on other cell types throughout the body. Our work creates a set of actionable hypotheses to better understand how deconditioned muscle may influence the function of sensory neurons that innervate the entire body.

Investigating the disproportionate rates of chronic pain and their related comorbidities between Black and non-Hispanic White (White) individuals is a growing area of interest, both in the healthcare community and in general society. Researchers have identified racial differences in chronic pain prevalence and severity, but still very little is known about the mechanisms underlying them. Current explanations for these differences have primarily focused on socioeconomic status and unequal healthcare between races as causal factors. Whereas these factors are informative, a racial gap still exists between Black and White individuals when these factors are controlled for. One potential cause of this racial gap in chronic pain is the differences in nutrition and dietary intake between groups. Certain foods play a key role in the inflammatory and oxidative stress pathways in the human body and could potentially influence the severity of the pain experience. Here, we review the previous literature on the surrounding topics and propose a potential mechanism to explain racial differences in the chronic pain population, based on established racial differences in diet and oxidative stress.

Guidelines for migraine prophylaxis suggest stopping medication after 6-12 months to reevaluate treatment appropriateness. The Italian Medicines Agency (AIFA) set a mandatory regulation to stop anti-CGRP (calcitonin gene related protein) pathway monoclonal antibody (anti-CGRP mAbs) treatments for 3 months after 12-months of treatment. Herein, we assess the effects of discontinuation and retreatment of anti-CGRP mAbs in resistant chronic migraine patients, evaluating predictive factors of sustained response.

The goal of this study was to analyze the reasons for delayed diagnosis of Guillain-Barre syndrome (GBS).

Pain catastrophizing (PC), defined as tendency to describe pain in more exaggerated terms, to ruminate more or to feel helpless about it. Main objective was to illuminate PC in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), revealing its prevalence and associations from a biopsychosocial perspective, including its association with health-related quality of life (HRQoL). Measures reflecting the biological, social and psychological perspective were recorded in RA, PsA and axSpA outpatients. Biological variables including demographics, disease activity and patient reported outcomes (PROs) along with variables reflecting psychological and social domains were collected. RAND12 questionnaire was used to explore HRQoL and standardized questionnaire was used to reveal pain catastrophizing score (PCS). 1229 patients were recruited (RA 580, PsA 394, axSpA 255). Mean (SD) PCS were for RA 1.88 (1.39), PsA 2.06 (1.45) and axSpA 2.27 (1.37). Proportion of pain catastrophizers (score ≥ 4) was not statistically different between RA (10.5%), PsA (12.7%) and axSpA (15.3%). Across all diagnoses, variables reflecting biological subjective domain explained more PCS variability (adjusted R 35.3-49.9%) than psychological (28.4-33.6%), social (22.4-28.4%) and biological objective (4.3-9.9%) domains. HRQoL was significantly lower in pain catastrophizers across all diagnoses. No substantial differences in proportion of pain catastrophizers between RA, PsA and axSpA patients were found. Higher PCS (score ≥ 4) was best explained by biological subjective measures and corresponded with inferior HRQoL in all diseases. Several biological objectives, psychological and social measures were also associated with higher PCS.

Temporomandibular disorders (TMD) patients can present clinically significant jaw pain fluctuations which can be debilitating and lead to poor global health. The Graded Chronic Pain Scale evaluates pain-related disability and its dichotomous grading (high/low impact pain) can determine patient care pathways and in general high-impact pain patients have worse treatment outcomes. Individuals with low-impact TMD pain are thought to have better psychosocial functioning, more favorable disease course, and better ability to control pain, while individuals with high-impact pain can present with higher levels of physical and psychological symptoms. Thereby, there is reason to believe that individuals with low- and high-impact TMD pain could experience different pain trajectories over time. Our primary objective was to determine if short-term jaw pain fluctuations serve as a clinical marker for the impact status of TMD pain. To this end, we estimated the association between high/low impact pain status and jaw pain fluctuations over three visits (≤ 21-day-period) in 30 TMD cases. Secondarily, we measured the association between jaw pain intensity and pressure pain thresholds (PPT) over the face and hand, the latter measurements compared to matched pain-free controls (n = 17). Jaw pain fluctuations were more frequent among high-impact pain cases (n = 15) than low-impact pain cases (n = 15) (OR 5.5; 95% CI 1.2, 26.4; p value = 0.033). Jaw pain ratings were not associated with PPT ratings (p value > 0.220), suggesting different mechanisms for clinical versus experimental pain. Results from this proof-of-concept study suggest that targeted treatments to reduce short-term pain fluctuations in high-impact TMD pain is a potential strategy to achieve improved patient perception of clinical pain management outcomes.

Zoster-associated pain (ZAP), which may cause anxiety, depression, and sleep disorders and reduce quality of life, is often refractory to current standard treatments. Studies have shown that pulsed radiofrequency (PRF) can alleviate ZAP and reduce the incidence of postherpetic neuralgia (PHN). This study aimed to explore the clinical characteristics associated with PRF responsiveness, develop a model for identifying risk factors of inadequate PRF management, and help clinicians make better decisions.

Migraine is a common neurovascular disorder that has a severe impact on the individual daily life. Atogepant (AGN-241689) is an orally ingested, small-molecule drugs belonging to calcitonin gene-related peptide receptor antagonist, which has been initiated for the prophylactic treatment of migraine. However, there is no comprehensive literature to study the efficacy and safety of atogepant for the treatment of migraine. In this article, we present a meta-analysis of the available studies.