The journal of pain : official journal of the American Pain Society
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Randomized Controlled Trial Multicenter Study
OPRM1 Methylation Contributes to Opioid Tolerance in Cancer Patients.
Cancer patients in pain require high doses of opioids and quickly become opioid-tolerant. Previous studies have shown that chronic cancer pain as well as high-dose opioid use lead to mu-opioid receptor downregulation. In this study we explore downregulation of the mu-opioid receptor gene (OPRM1), as a mechanism for opioid tolerance in the setting of opioid use for cancer pain. ⋯ We focus on 2 main cells within the cancer microenvironment: the cancer cell and the neuron. We show that targeted re-expression of mu-opioid receptor on cancer cells inhibits mechanical and thermal hypersensitivity, and prevents opioid tolerance, in the mouse model. The resultant analgesia and protection against opioid tolerance are likely due to preservation of mu-opioid receptor expression on the cancer-associated neurons.
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Randomized Controlled Trial Multicenter Study
A longitudinal randomized trial of the impact of consistent pain management for infant vaccinations on future vaccination distress.
The objective was to determine if consistent pain management during vaccine injections has a beneficial effect on future infant pain reactivity. This was a multicenter, longitudinal, double-blind, double-dummy, add-on, randomized controlled trial. Healthy infants were randomized to 1 of 4 add-on pain management regimens for all vaccinations in the first year of life: 1) placebo control (standard care), 2) parent video education about infant soothing (video), 3) video and oral sucrose solution (sucrose), 4) video and sucrose and topical liposomal lidocaine (lidocaine). ⋯ Altogether, 352 infants participated; characteristics did not differ among groups (P > .05). Pain scores did not differ among groups during baseline (P = .642), needle injection (P = .739), or recovery (P = .750) phases. In conclusion, there was no evidence of a long-term benefit of consistent use of pain interventions in the first year of life on future infant pain responsivity at 15-month vaccinations.
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We explored causal mediation of sleep quality and perceived stress in development of painful temporomandibular disorder (TMD). Sleep quality and perceived stress were assessed at baseline and quarterly intervals thereafter in 2,737 initially TMD-free adults in the Orofacial Pain Prospective Evaluation and Risk Assessment study (OPPERA) prospective cohort study. During follow-up, incident TMD cases were classified using research diagnostic criteria. Mediation analysis was conducted using a weighted Cox proportional hazards regression model that estimated hazard ratios (HRs) and 95% confidence limits (CL) of first-onset TMD. Models determined whether: 1) poor sleep quality during follow-up mediated the effect of baseline perceived stress on first-onset TMD, and 2) perceived stress during follow-up mediated the effect of baseline poor sleep quality on first-onset TMD. In both analyses, the total effect was decomposed into natural direct and indirect effects. Poor baseline sleep quality led to heightened perceived stress that then contributed to TMD development. When the total effect of poor sleep quality (HR = 2.10, CL = 1.76, 2.50) was decomposed, 34% of its effect was mediated by perceived stress (indirect effect HR = 1.29, CL = 1.06, 1.58). The effect of perceived stress on first-onset TMD was not mediated by sleep quality. Improving sleep may avert escalation of stress, limiting effects of both factors on TMD development. ⋯ Causal mediation analysis highlights mechanisms by which poor sleep quality promotes development of TMD. First, poor sleep quality exerts a direct effect on pain. Second, it triggers a heightened perception of stress, which acts as an intermediate factor in the causal pathway between poor sleep quality and first-onset TMD pain.
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Multicenter Study
Higher Prescription Opioid Dose is associated with Worse Patient-Reported Pain Outcomes and More Health Care Utilization.
Some previous research has examined pain-related variables on the basis of prescription opioid dose, but data from studies involving patient-reported outcomes have been limited. This study examined the relationships between prescription opioid dose and self-reported pain intensity, function, quality of life, and mental health. Participants were recruited from 2 large integrated health systems, Kaiser Permanente Northwest (n = 331) and VA Portland Health Care System (n = 186). ⋯ A statistically significant trend emerged where higher prescription opioid dose was associated with moderately sized effects including greater pain intensity, more impairments in functioning and quality of life, poorer self-efficacy for managing pain, greater fear avoidance, and more health care utilization. Rates of potential alcohol and substance use disorders also differed among groups. Findings from this evaluation reveal significant differences in pain-related and substance-related factors on the basis of prescription opioid dose.
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Pain acceptance is a robust predictor of adjustment to chronic pain; however, the dynamics of pain acceptance in daily life are largely unexamined. Furthermore, research on pain acceptance in those with pain and physical disability is needed. To examine pain acceptance in daily life, we collected 7 days of ecological momentary assessments of pain intensity and pain interference (5 times per day) with continuous accelerometry (physical activity) in 128 individuals with chronic pain and spinal cord injury. ⋯ The activities engagement component of pain acceptance was a slightly more robust driver of these interaction effects; whereas activities engagement significantly moderated the association between momentary pain and pain interference as well as physical activity, pain willingness exerted a significant moderating effect on the momentary association between pain intensity and pain interference only. These findings suggest that both components contribute to the decoupling effects of pain acceptance. Task persistence did not show the same moderating effects, indicating that pain acceptance may be unique from other types of behavioral pain coping in its ability to decouple expected associations between pain intensity, pain interference, and physical activity.