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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Comparative Study
Age differences in the time-course and magnitude of changes in circulating neuropeptides following pain evocation in humans.
This study tested the hypothesis that older adults would have a stronger response for substance P (facilitatory) but weaker response to β-endorphin (inhibitory), in magnitude as well as time course. Eight younger and 9 older adults underwent 3 experimental sessions using well validated laboratory pain models: cold pressor task, contact heat pain, and a nonpainful control. Blood was collected through an indwelling catheter at baseline and 3, 15, 30, 45, and 60 minutes after stimuli administration. Older adults had higher baseline levels of both neuropeptides suggesting increased peripheral activity compared with younger adults. After the cold pressor task, older adults demonstrated a quick and strong release of substance P with dramatic recovery, whereas young adults maintained a constant low-grade response. Unlike substance P, β-endorphin increased between 3 and 15 minutes for both groups with the upsurge substantially higher for older adults. After heat pain, younger adults had an immediate surge in circulating substance P and β-endorphin that was more pronounced than among older adults. However, levels of substance P for younger adults slowly tapered whereas they continued to climb for the older adults through 30 minutes. β-endorphin peaked at 30 minutes for both groups and returned to baseline. No changes were observed during the nonpainful control session. ⋯ Older adults had higher baseline levels of substance P and β-endorphin suggesting increased peripheral activity compared with younger adults. After pain evocation, older adults demonstrated a more intense early response for both neuropeptides suggesting peripheral mechanisms involved in the response to pain may change with age.
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Placebo analgesia, reductions in pain after administration of an inert treatment, is a well documented phenomenon. We report, to our knowledge, the first demonstration that placebo analgesia can be experienced when a sham analgesic is applied onto a rubber hand. ⋯ During synchronous visuotactile stimulation, pain was experienced on the rubber arm, and the application of the sham analgesic to the rubber arm significantly decreased the severity of reported pain. This shows that experience of the body can modulate expectations and the induction of placebo analgesia.
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Randomized Controlled Trial
Responsiveness and Minimally Important Differences for Four Patient-Reported Outcomes Measurement Information System (PROMIS) Short Forms: Physical Function, Pain Interference, Depression, and Anxiety in Knee Osteoarthritis.
Patient-Reported Outcomes Measurement Information System (PROMIS) instruments can provide valid, interpretable measures of health status among adults with osteoarthritis (OA). However, their ability to detect meaningful change over time is unknown. We evaluated the responsiveness and minimally important differences (MIDs) for 4 PROMIS Short Forms: Physical Function, Pain Interference, Depression, and Anxiety. We analyzed adults with symptomatic knee OA from our randomized trial comparing Tai Chi and physical therapy. Using baseline and 12-week scores, responsiveness was evaluated according to consensus standards by testing 6 a priori hypotheses of the correlations between PROMIS and legacy change scores. Responsiveness was considered high if ≥5 hypotheses were confirmed, and moderate if 3 or 4 were confirmed. MIDs were evaluated according to prospective change for people achieving previously-established MID on legacy comparators. The lowest and highest MIDs meeting a priori quality criteria formed a MID range for each PROMIS Short Form. Among 165 predominantly female (70%) and white (57%) participants, mean age was 61 years and body mass index was 33. PROMIS Physical Function had 5 confirmed hypotheses and Pain Interference, Depression, and Anxiety had 3 or 4. MID ranges were: Depression = 3.0 to 3.1; Anxiety = 2.3 to 3.4; Physical Function = 1.9 to 2.2; and Pain Interference = 2.35 to 2.4. PROMIS Physical Function has high responsiveness, and Depression, Anxiety, and Pain Interference have moderate responsiveness among adults with knee OA. We established the first MIDs for PROMIS in this population, and provided an important standard of reference to better apply or interpret PROMIS in future trials or clinical practice. ⋯ This study examined whether PROMIS Short Form instruments (Physical Function, Pain Interference, Depression, and Anxiety) were able to detect change over time among adults with knee OA, and provided minimally important change estimates for each measure. This standard of reference can help apply or interpret these instruments in the future.