Pain
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The aims of this review were to systematically identify the current evidence base of placebo (or "sham") randomised controlled trials (RCTs) of spinal cord stimulation (SCS) for neuropathic pain and to undertake a meta-analysis to investigate the effectiveness of SCS when compared with a placebo comparator arm. Electronic databases were searched from inception until January 2019 for RCTs of SCS using a placebo/sham control. Searches identified 8 eligible placebo-controlled randomised trials of SCS for neuropathic pain. ⋯ Our analyses suggest that the magnitude of treatment effect varies across trials and, in part, depends on the quality of patient blinding and minimisation of carryover effects. Improved reporting and further methodological research is needed into placebo and blinding approaches in SCS trials. Furthermore, we introduce a differentiation between placebo and sham concepts that may be generalisable to trials evaluating surgical or medical procedures.
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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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A child maltreatment history is reported more frequently among adults with chronic pain compared with the general population; unfortunately, studies have primarily relied upon retrospective maltreatment reports by adults with chronic pain. This prospective study assessed pain symptoms in a cohort of young adult women with a documented history of child maltreatment, compared with a matched cohort of women who did not experience childhood maltreatment. Young women (N = 477) were recruited between ages 14 to 17 years and followed annually to age 19. ⋯ As adults, women who had experienced child maltreatment reported higher pain intensity, a greater number of pain locations, and were more likely to experience pain in the previous week than nonmaltreated women. Adolescent post-traumatic stress partially explained the effects of maltreatment on pain. Young adult women who experienced child maltreatment are at higher risk of pain, particularly when they also experienced post-traumatic stress as adolescents.