Human Studies

Chronic low back pain (CLBP) has a significant negative impact on daily functioning, particularly for those with challenges coping adaptively with ongoing pain. However, the dynamics of pain coping in daily life remain understudied. Therefore, we examined the extent to which pain intensity interferes with daily activities, and assessed whether pain coping strategies (as assessed using daily diaries) moderated this link.

To examine neural mechanisms underlying photophobia in individuals with chronic ocular surface pain using functional magnetic resonance imaging (fMRI).

The objective of this study was to determine the effect of enhancing conventional care for people with chronic painful temporomandibular disorders (TMD) with an individualised contemporary pain science education (PSE) intervention. In this randomized controlled trial, a consecutive sample of 148 participants (18 to 55 years of age) was randomized into two groups: PSE-enhanced conventional care or Conventional care alone. Conventional care involved a six-week, 12-session manual therapy and exercise program. The PSE enhancement involved two sessions of modern PSE, undertaken in the first two treatment sessions. Primary outcomes were pain intensity, assessed with a numeric pain rating scale, and disability, assessed with the craniofacial pain and disability inventory, post-treatment. Linear mixed model analyses were used to investigate between-group differences over time. There was a statistically and clinically meaningful effect of PSE enhancement on disability (Mean Difference = 6.1, 95% CI: 3.3 to 8.8), but not on pain intensity, post-treatment. Secondary analyses suggested clinically meaningful benefit of PSE enhancement on pain and disability ratings at 10-week and 18-week follow-ups, raising the possibility that preceding conventional care with a PSE intervention may result in long-term benefits. Perspective: The addition of modern Pain Science Education (PSE) intervention improved disability for people with chronic TMD receiving manual therapy and exercise, but not pain. A mean difference in pain and disability favoring the PSE group at the 10- and 18-week follow-ups, respectively, suggests that PSE addition resulted in longer-lasting effects. Trial registration: NCT03926767. Registered on April 29, 2019. https://clinicaltrials.gov/ct2/show/NCT03926767.

Treatment of chronic lower back pain (CLBP) should be stratified for best medical and economic outcome. To improve the targeting of potential participants for exclusive therapy offers from payers, Freytag et al. developed a tool to classify back pain chronicity classes (CC) based on claim data. The aim of this study was to evaluate the criterion validity of the model. Administrative claim data and self-reported patient information from 3,506 participants (2014-2021) in a private health insurance health management programme in Germany were used to validate the tool. Sensitivity, specificity, and Matthews' correlation coefficient (MCC) were calculated comparing the prediction with actual grades based on von Korff's graded chronic pain scale (GCPS). The secondary outcome was an updated view on direct health care costs (€) of patients with back pain (BP) grouped by GCPS. Results showed a fair correlation between predicted CC and actual GCPS grades. A total of 69.7% of all cases were correctly classified. Sensitivity and specificity rates of 54.6 and 76.4% underlined precision. Correlation between CC and GCPS with an MCC of 0.304 also indicated a fair relationship between prediction and observation. Cost data could be clearly grouped by GCPS: the higher the grade, the higher the costs and the use of health care. This was the first study to compare the predicted severity of BP using claim data with the actual severity of BP by GCPS. Based on the results, the usage of CC as a single tool to determine who receives CLBP treatment cannot be recommended. CC is a good tool to segment candidates for specific types of intervention in BP. However, it cannot replace a medical screening at the beginning of an intervention, as the rate of false negatives is too high. Trial registration The study was conducted using routinely collected data from an intervention, which was previously evaluated and registered retrospectively in the German Registry of Clinical Trials under DRKS00015463 (04/09/2018). Informed consent and the self-reported questionnaire have remained unchanged since the study and, therefore, are still valid according to the ethics proposal.

The mechanisms underlying neuropathic pain remain unclear. Lysophosphatidic acid (LPA) is a bioactive phospholipid derived mainly from lysophosphatidylcholine (LPC) by extracellular autotaxin (ATX), and has attracted attention as a candidate biomarker of neuropathic pain. We aimed to investigate the levels of LPA, LPC, and ATX in patients with lumbar spinal canal stenosis (LSCS) or other neuropathic pain diseases, and to distinguish the underlying mechanism of LSCS from other neuropathic pain conditions. Furthermore, the levels of phosphorylated neurofilament heavy chain (pNF-H), an objective surrogate marker of axonal damage, were also measured. Cerebrospinal fluid (CSF) samples were obtained from 56 patients with LSCS (n = 31) and various etiologies other than LSCS (n = 25). Patients with LSCS complained of pain intensity comparable to that of patients without LSCS. The LPA levels were significantly higher in patients with LSCS than in non-LSCS patients, while the ATX levels were significantly lower. However, the differences in LPC and pNF-H levels between the two patient groups were not significant. The LPA/LPC ratio was significantly higher in the LSCS group. Notably, the difference in LPA between the two groups diminished in the analysis of covariance (ANCOVA) with ATX as a covariate. Thus, it helped to reveal that LPA synthesis in patients with LSCS depends more efficiently on ATX than in non-LSCS neuropathic pain patients with other etiologies. Our findings further suggest that the triad of LPA, LPC, and ATX in LSCS may contribute to the development and maintenance of neuropathic pain in a manner different from non-LSCS neuropathic conditions.

Erenumab, an anti-calcitonin gene-related peptide (CGRP) receptor monoclonal antibody (mAb), was approved by the US Food and Drug Administration in May 2018. Constipation with serious complications was added to the Warning and Precautions section in the erenumab Prescribing Information in October 2019 after events were observed during post-marketing surveillance. We aimed to assess and compare the risk of inpatient constipation, and, separately, inpatient constipation with serious complications, among patients with migraine treated with CGRP mAbs and standard of care antiepileptic drugs (AEDs).

Temporomandibular disorders (TMD) symptoms develop into chronic pain for some patients, but the reasons for this are unclear. Psychosocial factors and chronic overlapping pain conditions are believed to contribute to the development of pain-related disability. We examined the role of jaw function, negative and positive psychological factors, chronic overlapping pain conditions (COPCs) on pain-related disability while controlling for demographic variables. We collected demographics, medical and psychosocial history, and the Graded Chronic Pain Scale, a measure of pain intensity and pain interference from 400 participants with chronic TMD. Structural equation modeling was used to assess a model of of COPCs and the latent variables of psychological unease (pain catastrophizing, somatic symptoms, and negative affect), positive valence factors (optimism and positive affect), jaw function (chewing, opening, and expression limitation), and pain-related disability (pain intensity and pain interference) while controlling for demographic variables. We achieved good fit of a parsimonious model (root-mean-square error of approximation = .063 (90% CI) [.051-.075]), comparative fit index =.942, standard root-mean-square residual = .067). Jaw function was the strongest latent variable predictor, followed by psychological unease and COPCs suggesting resources focused on improving joint function, psychosocial support, and management of COPCs will improve pain-related disability in TMDs. These findings not only increase the body of knowledge related to TMD clinical phenotypes but also, have translational impact in further supporting the potential value of targeting physical therapy such as jaw exercise along with psychological interventions as multidisciplinary nonpharmacological therapeutic solutions.