Human Studies

Genetic variation in melanocortin-1 receptor (MC1R) has a known role in red hair. Studies on responses to noxious stimuli in red-haired individuals have also been conducted, with mixed findings. To investigate a possible divergence between variants responsible for red hair and pain sensitivity, we performed a gene-wide association analysis in the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) cohort. All genotyped (17) MC1R variants were tested for association with heat pain temporal summation and sensitivity. Our analyses showed an association for pain sensitivity with the 5'-UTR, tagged by rs3212361, and one missense variant, rs885479 (R163Q), previously shown to be weakly associated with red hair. For both variants, the minor allele was protective. These results were validated in the 500,000-person U.K. Biobank (UKBB) cohort, where the minor alleles of rs3212361 and rs885479 were associated with a reduced count of persistent pain conditions as well as individual pain conditions. Haplotype association analysis revealed a possible joint effect from the two individual variants. The 5'-UTR variant rs3212361 was further identified as an expression quantitative trait locus (eQTL), associated with reduced transcript levels of MC1R in the brain and in the peripheral tibial nerve. Hair colour association analysis of the loss-of-function 5'-UTR rs3212361 allele identified association with red hair, and red hair colour itself was associated with a reduced count of persistent pain conditions. Together, our results suggest that primarily different mechanisms – affecting expression levels versus protein activity – mediated by different genetic variants in the MC1R locus contribute to red hair and pain.

Despite guidelines, painful neuropathy is often inappropriately treated. We aimed to determine the effectiveness of a clinical decision support system on guideline-recommended medication utilization.

To evaluate the national general prevalence of postoperative pain and the associated organizational/structural factors related to the provision of health care services.

Extensive literature has investigated the role of serotonin (5-HT) in the control of central dopamine (DA) systems, and their dysfunction in pathological conditions. 5-HT stimulates local DA release in striatal regions via activation of various receptors including serotonin receptor-3 (5-HT3). Several studies have related polymorphisms (SNPs) in the serotonin receptor-3 (HTR3) genes to be associated with pain modulation and endogenous pain suppression. A few studies suggested a functional role of 5'UTR SNP in the serotonergic receptor HTR3A gene (rs1062613) in the development of chronic pain and Fibromyalgia syndrome (FMS) in particular. Here, we investigated the effect of a 5'UTR SNP in the serotonergic receptor HTR3A gene (rs1062613) on striatal dopamine D2/D3 receptor (DRD2) availability and reward-associated DA release in response to unpredictable monetary rewards in 23 women with FMS and 17 age-matched healthy female controls. Furthermore, we aimed to examine if SNP rs1062613 is associated with thermal pain and pain tolerance thresholds.

Many medically-refractory trigeminal neuralgia patients are non-responders to surgical treatment. Few studies have explored how trigeminal nerve characteristics relate to surgical outcome, and none have investigated the relationship between subcortical brain structure and treatment outcomes.

The purpose of this work is to determine the relationship between biomarkers of inflammation, structure, and pain with radiographic disc space narrowing (DSN) in community-based participants. A total of 74 participants (37 cases and 37 controls) enrolled in the Johnston County Osteoarthritis (OA) Project during 2006-2010 were selected. Cases had at least mild radiographic DSN and low back pain (LBP). Controls had neither radiographic evidence of DSN nor LBP. Measured analytes from human serum included N-cadherin, Keratin-19, Lumican, CXCL6, RANTES, IL-17, IL-6, BDNF, OPG and NPY. A standard dolorimeter measured pressure-pain threshold. Coefficients of variation (CVs) were used to evaluate inter- and intra-assay reliability. Participants with similar biomarker profiles were grouped together using cluster analysis. Binomial regression models were used to estimate risk ratios (RR) and 95% confidence intervals (CI) in propensity score matched models. Significant associations were found between radiographic DSN and OPG (RR=3.90 95% CI 1.83, 8.31), IL-6 (RR=2.54 95% CI 1.92, 3.36) and NPY (RR=2.06 95% CI 1.62, 2.63). Relative to a cluster with low levels of biomarkers, a cluster representing elevated levels of OPG, RANTES, Lumican, Keratin-19 and NPY (RR=3.04 95% CI 1.22, 7.54) and a cluster representing elevated levels of NPY (RR=2.91 95% CI 1.15, 7.39) were significantly associated with radiographic DSN. Clinical Significance: These findings suggest that individual and combinations of biochemical biomarkers may reflect radiographic DSN. This is just one step towards understanding the relationships between biochemical biomarkers and DSN that may lead to improved intervention delivery. This article is protected by copyright. All rights reserved.

Patellofemoral pain (PFP) is a common complaint among young sports active adolescents. This study evaluated the longitudinal changes in pronociceptive and antinociceptive mechanisms in young adolescents with PFP, their impact on prognosis, and responsiveness to treatment. Adolescents (N = 151, aged 10-14 years) diagnosed with PFP were compared with age-matched controls (N = 50) and subsequently tracked while participating in an intervention focussed on activity modification. They underwent quantitative sensory testing at baseline (preintervention), 4 weeks (during initial treatment), and 12 weeks (after treatment). Pressure pain thresholds (PPTs) were recorded on the knee, shin, and elbow. Temporal summation of pain (TSP) was assessed by the increase in pain intensity during 10 repeated cuff pressure pain stimulations on the leg. Conditioned pain modulation (CPM) was defined as change in cuff pain thresholds on one leg, during painful cuff conditioning on the contralateral leg. At baseline, adolescents with PFP had decreased PPTs at the knee, shin, and elbow (P < 0.001) as well as more facilitated TSP (P < 0.05) compared with controls. For CPM at baseline, controls displayed an increase in cuff pain thresholds during conditioning (P < 0.05), while those with PFP did not. More facilitated baseline TSP was associated with less improvements in pain intensity during the intervention (P < 0.01). Pressure pain thresholds increased at both follow-ups (P < 0.001), and the increased PPTs were associated with decreases in pain intensity (r = 0.316; P < 0.001). Overall, TSP remained facilitated at follow-ups, and there was no change in CPM. This is the first study to demonstrate a pronociceptive mechanism as a prognostic factor in young adolescents with PFP.