Human Studies

Despite the known involvement of depression in chronic pain, the association between persistence with and adherence to antidepressant medication and onset of chronic pain in patients with depression remains unclear.

Gerontological research reveals considerable interindividual variability in aging phenotypes, which has motivated research efforts to identify 'aging biomarkers.' Aging biomarkers are used to calculate biological age, which are better predictors of disease risk and residual lifespan when compared to chronological age alone. Emerging evidence using the epigenetic clock as an aging biomarker supports highly reliable individualized predictions about future health. The current study aimed to determine whether an epigenetic aging biomarker was associated with chronic pain in older adults (60-83 years old). A subset of participants (n=29) in the Neuromodulatory Examination of Pain and Mobility Across the Lifespan (NEPAL) study underwent a blood draw, demographic, psychological, cognitive and pain assessments. We estimated Horvath's epigenetic clock and calculated the difference between epigenetic age and chronological age that has been previously reported to predict overall mortality risk. Older individuals without chronic pain (n=9) had significantly "younger" epigenetic age compared to those with chronic pain (n=20, p<0.05). Older epigenetic age was associated with greater pain during daily activities (r=0.494, p=0.010) and anatomical pain sites (r=0.741, p<0.001), but not pain frequency/duration. An older epigenetic age was also associated with higher vibratory detection thresholds (r=0.490, p=0.021), heat pain thresholds (r=-0.478, p=0.028), and pressure pain thresholds at the trapezius (r=-0.571, p=0.006), but not thermal detection, pressure pain at the quadriceps or pain inhibition (p's>0.05). Epigenetic aging was associated with greater emotional stability (r=-0.461, p=0.027), conscientiousness (r=-0.549, p=0.007) and lower extraversion (r=0.414, p=0.049), but not depression or affect (p's>0.05). Epigenetic aging was also associated with lower episodic (r=-0.698, p=0.001) and working memory (r=-0.760, p<0.001). Our findings suggest that chronic pain is associated with accelerated epigenetic aging in healthy, community-dwelling older individuals and future studies with larger samples are needed to confirm our findings. An aging biomarker such as the epigenetic clock may help identify people with chronic pain at greater risk of functional decline and poorer health outcomes.

Slow brushing over the skin activates C-tactile nerve fibers that transmit pleasant tactile experiences in healthy subjects, leading to an inverted U-shaped velocity dependence of ratings: C-tactile optimal stroking stimulations are rated as more pleasant than slower or faster stimulations. Chronic pain diseases such as postherpetic neuralgia (PHN) and complex regional pain syndrome show altered C-fiber innervation density, sensory loss, and pain sensitization.

Evidence supports but is inconclusive that sensitization contributes to chronic pain in some adults with sickle cell disease (SCD). We determined the prevalence of pain sensitization among adults with SCD pain compared with pain-free healthy adults. In a cross sectional, single session study of 186 African American outpatients with SCD pain (age 18-74 years, 59% female) and 124 healthy age, gender, and race matched control subjects (age 18-69 years, 49% female), we compared responses to standard thermal (Medoc TSA II) and mechanical stimuli (von Frey filaments). Although we observed no significant differences in thermal thresholds between controls and patients, patients with SCD had lower pain thresholds to mechanical stimuli and reported higher pain intensity scores to all thermal and mechanical stimuli at a non-painful body site. Compared with controls, about twice as many patients with SCD showed sensitization: 12% versus 23% at the anterior forearm site (p=.02), and 16% versus 32% across three tested sites (p=.004). Among patients with SCD, 18% exhibited some element of central sensitization. Findings indicate that persistent allodynia and hyperalgesia can be part of the SCD pain experience and should be considered when selecting therapies for SCD pain. Perspective: Compared with matched healthy controls, quantitative sensory testing in adults with pain and sickle cell disease (SCD) demonstrates higher prevalence of sensitization, including central sensitization. The findings of allodynia and hyperalgesia may indicate neuropathic pain and could contribute to a paradigm shift in assessment and treatment of SCD pain.

Evidence from genome-wide and candidate gene association studies, familial aggregation and linkage analyses demonstrate the genetic contribution to fibromyalgia (FM) disease. This study aimed to identify genetic biomarkers of FM and its related comorbid disorders, by exploring 41 polymorphisms potentially involved in FM pathogenesis in families with at least one patient with FM.

To assess the efficacy of three months of antibiotic treatment compared with placebo in patients with chronic low back pain, previous disc herniation, and vertebral endplate changes (Modic changes).