Human Studies

The composition of the subchondral bone marrow and cartilage endplate (CEP) could affect intervertebral disc health by influencing vertebral perfusion and nutrient diffusion. However, the relative contributions of these factors to disc degeneration in patients with chronic low back pain (cLBP) have not been quantified. The goal of this study was to use compositional biomarkers derived from quantitative MRI to establish how CEP composition (surrogate for permeability) and vertebral bone marrow fat fraction (BMFF, surrogate for perfusion) relate to disc degeneration.

Complex regional pain syndrome (CRPS) is a painful condition commonly accompanied by movement disturbances and often affects the upper limbs. The basal ganglia motor loop is central to movement, however, non-motor basal ganglia loops are involved in pain, sensory integration, visual processing, cognition, and emotion. Systematic evaluation of each basal ganglia functional loop and its relation to motor and non-motor disturbances in CRPS has not been investigated. We recruited 15 upper limb CRPS and 45 matched healthy control subjects. Using functional magnetic resonance imaging, infraslow oscillations (ISO) and resting-state functional connectivity in motor and non-motor basal ganglia loops were investigated using putamen and caudate seeds. Compared to controls, CRPS subjects displayed increased ISO power in the putamen contralateral to the CRPS affected limb, specifically, in contralateral putamen areas representing the supplementary motor area hand, motor hand, and motor tongue. Furthermore, compared to controls, CRPS subjects displayed increased resting connectivity between these putaminal areas as well as from the caudate body to cortical areas such as the primary motor cortex, supplementary and cingulate motor areas, parietal association areas, and the orbitofrontal cortex. These findings demonstrate changes in basal ganglia loop function in CRPS subjects and may underpin motor disturbances of CRPS.

Quantitative Sensory Testing (QST) is used to test somatosensory functioning in patients with low back pain (LBP) and most performed on people with chronic LBP in secondary/tertiary health care facilities. Studies using QST-testing on LBP populations in primary care are scarce. Central Sensitization Inventory (CSI) measures central sensitization (CS)-related symptoms and studies investigating the differences between QST-testing and participants with LBP with a positive and negative score on the CSI questionnaire are also rare. This case-control study investigates differences of an extensive QST-measurement between patients with acute, chronic LBP and healthy controls in primary care. Secondary aim is to investigate differences of an extensive QST-measurement between "CS" and "no-CS" group.

To explore how young adults with chronic pain define a successful transition from pediatric to adult chronic pain care, and how they would like to be empowered to achieve a successful transition.

Chronic postsurgical pain (CPSP) is defined by pain intensity and pain-related functional interference. This study included measures of function in a composite score of patient-reported outcomes (PROs) to investigate the incidence of CPSP. Registry data were analyzed for PROs one day and 12 months postoperatively. Based on pain intensity and pain-related interference with function, patients were allocated to the groups "CPSPF" (at least moderate pain with interference), "Mixed" (milder symptoms) and "No CPSPF". The incidence of CPSPF was compared to CPSP rates referring to published data. Variables associated with the PRO-12 score (composite PROs at 12 months; NRS 0-10) were analyzed by linear regression analysis. Of 2319 patients, 8.6%, 32.5% and 58.9% were allocated to the groups CPSPF, Mixed and No CPSPF. Exclusion of patients whose pain scores did not increase compared to the preoperative status, resulted in a 3.3% incidence. Of the patients without pre-existing pain, 4.1% had CPSPF. Previously published pain cut-offs of NRS >0, ≥3 or ≥4, used to define CPSP, produced rates of 37.5%, 9.7% and 5.7%. Pre-existing chronic pain, pre-operative opioid medication and type of surgery were associated with the PRO-12 score (all p<0.05). Opioid doses and PROs 24 hours postoperatively improved the fit of the regression model. A more comprehensive assessment of pain and interference resulted in lower CPSP rates than previously reported. Although inclusion of CPSP in the ICD-11 is a welcome step, evaluation of pain characteristics would be helpful in differentiation between CPSPF and continuation of pre-existing chronic pain.

Children with acute and chronic illness undergo frequent, painful, and distressing procedures.

Gout is a prevalent and painful inflammatory arthritis, and its global burden continues to rise. Intense pain induced by gout attacks is a major complication of gout.However, systematic studies of gout inflammation and pain are lacking. Using a monosodium urate (MSU) crystal-induced gout model, we performed genome-wide transcriptome analysis of the inflamed ankle joint, dorsal root ganglion (DRG), and spinal cord of gouty mice. Our results revealed important transcriptional changes, including highly elevated inflammation and broad activation of immune pathways in both the joint and the nervous system, in gouty mice. Integrated analysis showed that there was a remarkable overlap between our RNAseq and human genome-wide association study (GWAS) of gout; for example, the risk gene, stanniocalcin-1 (STC1) showed significant upregulation in all three tissues. Interestingly, when compared to the transcriptomes of human osteoarthritis (OA) and rheumatoid arthritis (RA) joint tissues, we identified significant upregulation of cAMP/cyclic nucleotide-mediated signaling shared between gouty mice and human OA with high knee pain, which may provide excellent drug targets to relieve gout pain. Furthermore, we investigated the common and distinct transcriptomic features of gouty, inflammatory pain, and neuropathic pain mouse models in their DRG and spinal cord tissues. Moreover, we discovered distinct sets of genes with significant differential alternative splicing or differential transcript usage (DTU) in each tissue, which were largely not detected by conventional differential gene expression analysis approaches. Based on these results, our study provided a more accurate and comprehensive depiction of transcriptomic alterations related to gout inflammation and pain.

To examine the possible bidirectional association between insomnia and comorbid chronic low back pain (LBP) and lower limb pain and to explore whether high-sensitivity C-reactive protein (hsCRP) amplifies these associations.

About 1% of children and adolescents worldwide are affected by plaque psoriasis.