The journal of pain : official journal of the American Pain Society
-
Comparative Study
Soluble epoxide hydrolase inhibition is antinociceptive in a mouse model of diabetic neuropathy.
Neuropathic pain is currently an insufficiently treated clinical condition. There remains a critical need for efficacious therapies without severe side effects to treat the uniquely persistent and tonic pain of neuropathy. Inhibitors of the soluble epoxide hydrolase (sEH) enzyme that stabilize endogenous epoxy fatty acids have demonstrated antihyperalgesia in clinical chronic inflammatory pain and modeled neuropathic pain. Recently, the conditioned place preference assay has been used to evaluate the tonic nature of neuropathy in several animal models. The current experiments use the conditioned place preference assay alongside withdrawal thresholds to investigate the antihyperalgesic efficacy of sEH inhibitors in a murine model of diabetic neuropathy. Here, the sEH inhibitor trans-4-[4-(3-trifluoromethoxyphenyl-1-ureido)-cyclohexyloxy]-benzoic acid (t-TUCB) at 10 mg/kg induced a robust place preference in diabetic neuropathic mice representative of pain relief. Importantly, this effect was absent both in control mice and in sEH-knockout mice at the same dose, indicating that t-TUCB is not positively reinforcing or rewarding. When compared to gabapentin, t-TUCB elicited a similar degree of withdrawal threshold improvement without the same degree of spontaneous locomotion decline in neuropathic mice. Overall, these experiments show that inhibiting the sEH enzyme attenuates chronic pain and offers an alternative to current side-effect-limited therapies to meet this clinical need. ⋯ These experiments demonstrate antihyperalgesia in a murine chronic pain model mediated by inhibiting the sEH enzyme. The results of this study indicate that inhibiting the sEH is a promising alternative for blocking chronic pain.
-
Most studies on pain focus on specific disorders, which makes it difficult to compare characteristics across different types of pain symptoms. In this large population-based study, we examine the prevalence and comorbidity patterns among pain symptoms across a wide range of anatomic sites (back, neck, head, abdomen, joints, chest, face, teeth, and "other") in relation to anxious depression and a range of demographic, health, and lifestyle variables. Self-report data were collected in 11,787 adult participants of The Netherlands Twin Registry (mean age 44.5 years, 62% female), including twins and relatives of twins. Headache and abdominal pain were strongly associated with female sex, whereas chest pain and toothache were not. Joint pain strongly increased with age, whereas headache and abdominal pain decreased with age. Most other pain sites were only weakly associated with age. A highly consistent pattern of comorbidity was observed: All pain symptoms were correlated with all other pain symptoms, as well as with anxious depression. Frequent and widespread pain (ie, pain at multiple sites) was most strongly associated with anxious depression. These observations reflect important differences between specific pain symptoms, suggesting partly separate etiologies, but also highlight the importance of shared mechanisms underlying pain symptoms in general. ⋯ The association of pain with sex and age strongly depends on pain location. However, all pain sites are consistently associated with other pain sites as well as with anxious depression. This provides important clues with respect to both similarities and differences in the mechanisms underlying different types of pain.
-
Accountability has been shown to affect clinical judgments among health care providers in several ways. It may increase a provider's motivation for accuracy, leading to more deliberative judgments, or it may enhance biases that evaluators consistently demonstrate with patients with chronic pain. In this study, medical students read a vignette about a hypothetical patient referred for evaluation of severe low back pain by the Office of Vocational Rehabilitation. Accountability to the patient was either weak (consultative 1-time evaluation) or strong (ongoing primary care provision); societal accountability was either weak (evaluation information as secondary source for disability determination) or strong (evaluation information primary to disability determination). Participants then made judgments regarding validity of the patient's presentation, influence of psychosocial factors on the presentation, and patient's level of pain, distress, and disability, and completed an empathy measure. Results showed that empathy had strong associations with symptom validity and severity judgments. With empathy as a covariate, 3 crossover interactions emerged. Judgments of symptom validity were lower when the 2 forms of accountability were inconsistent (ie, one weak and the other strong) than when they were consistent (ie, both weak or both strong). Likewise, judgments of psychosocial factors and pain/distress/disability were higher under consistent accountability conditions than when accountability conditions were inconsistent. This pattern may imply conflict avoidance or self-protection as a motivation for judgments under inconsistent accountability. This study demonstrated that role demands can affect symptom judgments in complex ways, and that empathy may play both direct and moderating roles. Because physicians are the primary gatekeepers regarding disability determination in both consultative and treating roles, accountability may have significant mediating effects on such determinations. ⋯ This study demonstrated that medical student judgments of pain-related symptoms were strongly associated with their levels of empathic concern. Student judgments of symptom validity and psychosocial influences on patient adjustment were differentially affected by their level of accountability to the patient and society in a disability determination process.
-
The aim of this study was to assess the economic cost of chronic pain among adolescents receiving interdisciplinary pain treatment. Information was gathered from 149 adolescents (ages 10-17) presenting for evaluation and treatment at interdisciplinary pain clinics in the United States. Parents completed a validated measure of family economic attributes, the Client Service Receipt Inventory, to report on health service use and productivity losses due to their child's chronic pain retrospectively over 12 months. Health care costs were calculated by multiplying reported utilization estimates by unit visit costs from the 2010 Medical Expenditure Panel Survey. The estimated mean and median costs per participant were $11,787 and $6,770, respectively. Costs were concentrated in a small group of participants; the top 5% of those patients incurring the highest costs accounted for 30% of total costs, whereas the lower 75% of participants accounted for only 34% of costs. Total costs to society for adolescents with moderate to severe chronic pain were extrapolated to $19.5 billion annually in the United States. The cost of adolescent chronic pain presents a substantial economic burden to families and society. Future research should focus on predictors of increased health services use and costs in adolescents with chronic pain. ⋯ This cost of illness study comprehensively estimates the economic costs of chronic pain in a cohort of treatment-seeking adolescents. The primary driver of costs was direct medical costs followed by productivity losses. Because of its economic impact, policy makers should invest resources in the prevention, diagnosis, and treatment of chronic pediatric pain.