Pain
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Rescue medication is commonly offered to participants in placebo-controlled trials of analgesic drugs. The use of pain medication in addition to the placebo or experimental drug may complicate the interpretation of effects and tolerability, but this issue has received little methodological attention. This study examined the handling and reporting of rescue and concomitant analgesic use in trials of pharmacotherapy for neuropathic pain and low back pain. ⋯ More than one-third of the trials permitting rescue medication did not report the actual rescue drug consumption, and over half of the trials allowing concomitant analgesics did not report whether intake changed during the trial. Only 22 (19%) of the trials permitting rescue medication included complete information about whether rescue medication was used as an outcome, specified the drugs used, specified how consumption was assessed and measured, and reported and analyzed the use of rescue medication in each trial arm. Our findings suggest that poorly described procedures and incomplete reporting are likely to hinder the interpretation, critical appraisal, and replication of trial results.
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The objective of this study was to examine pain as a predictor of frailty over 18 years of follow-up among older Mexican Americans who were nonfrail at baseline. Data were from a prospective cohort study of 1545 community-dwelling Mexican Americans aged ≥67 years from the Hispanic Established Populations for the Epidemiological Study of the Elderly (1995/1996-2012/2013). Frailty was defined as meeting 2 or more of the following: unintentional weight loss of >10 pounds, weakness, self-reported exhaustion, and slowness. ⋯ Female participants and those with higher levels of education and high Mini-Mental State Examination scores were less at risk. In conclusion, pain was a significantly predictor of frailty. Early assessment and better management of pain may prevent early onset of frailty in older Mexican Americans.
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Chemotherapy-induced neuropathic pain (CINP) in both sexes compromises many current chemotherapeutics and lacks an FDA-approved therapy. We recently identified the sphingosine-1-phosphate receptor subtype 1 (S1PR1) and A3 adenosine receptor subtype (A3AR) as novel targets for therapeutic intervention. Our work in male rodents using paclitaxel, oxaliplatin, and bortezomib showed robust inhibition of CINP with either S1PR1 antagonists or A3AR agonists. ⋯ Thus, alternative mechanisms beyond receptor expression may account for sex differences in response to S1PR1 antagonists. Morphine and duloxetine, both clinical analgesics, reversed BINP in female mice, demonstrating that the lack of response is specific to S1PR1 and A3AR agents. Our findings suggest that A3AR- and S1PR1-based therapies are not viable approaches in preventing and treating BINP in females and should inform future clinical trials of these drugs as adjuncts to chemotherapy.
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It is often assumed that there are 2 types of pain patients: those who respond well to efficacious pain therapies and those who do not respond at all, with few people in the middle. This assumption is based on research that claims that changes in pain intensity have a bimodal distribution. The claim of bimodality has led to calls for a change in how pain clinical trials are designed and analyzed, eg, performing "responder" analyses instead of comparing group mean values to evaluate the treatment effect. ⋯ We found that the improper construction of histograms, using unequal bin widths, was the principal flaw leading to the bimodality claim, along with the use of the oft-criticized baseline observation carried forward method for imputing missing data also serving as a contributing factor. Properly constructed histograms of absolute change in pain intensity using equal bin widths, combined with more principled methods for handling missing data, resulted in distributions that had a more unimodal appearance. Although our findings neither support nor refute the hypothesis that distinct populations of "responders" and "nonresponders" to pain interventions exist, the analyses presented in earlier work do not provide support for this hypothesis, nor for the recommendation that pain clinical trials prioritize "responder" analyses, a less efficient analysis strategy.