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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The investigation of neurotransmitter systems in placebo and nocebo effects has improved our understanding of these phenomena. Yet, most studies involve healthy participants. Because the pain modulatory system may differ in healthy participants and patients with chronic pain, it is important to investigate the evidence for neurotransmitter involvement in placebo and nocebo effects in each of these populations. ⋯ Overall, research has come a long way in specifying the neurotransmitter systems involved in placebo effects in healthy participants. Yet, evidence for the involvement of neurotransmitter systems in placebo effects in patients with chronic pain and in nocebo effects in healthy participants and patients is scarce. Based on the existing evidence, this systematic review suggests that knowledge obtained in healthy participants may not necessarily be transferred to chronic 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.