Papers of the Week

This systematic review and meta-analysis investigated the effects of non-pharmacological manipulations on experimentally induced secondary hypersensitivity in pain-free humans. We investigated the magnitude (change/difference of follow-up ratings from pre-manipulation ratings) of secondary hypersensitivity (primary outcome), and surface area of secondary hypersensitivity (secondary outcome), in 27 studies with 847 participants. Risk of bias assessment concluded most studies (23 of 27) had unclear or high risk of performance and detection bias. Further, two (of 27) studies had high risk of measurement bias. Datasets were pooled by method of manipulation and outcome. Magnitude of secondary hypersensitivity was decreased by diverting attention, anodal transcranial direct current stimulation, or emotional disclosure; increased by directing attention towards the induction site, nicotine deprivation, or negative suggestion; and unaffected by cathodal transcranial direct current stimulation or thermal change. Area of secondary hypersensitivity was decreased by anodal transcranial direct current stimulation, emotional disclosure, cognitive behavioural therapy, hyperbaric oxygen therapy, placebo analgesia, or spinal manipulation; increased by directing attention to the induction site, nicotine deprivation, or sleep disruption (in males only); and unaffected by cathodal transcranial direct current stimulation, thermal change, acupuncture, or electroacupuncture. Meta-analytical pooling was only appropriate for studies that used transcranial direct current stimulation (primary outcome) and hyperbaric oxygen therapy (secondary outcome) given the high clinical heterogeneity among the studies and unavailability of data. The evidence base for this question remains small. We discuss opportunities to improve methodological rigour including manipulation checks, structured blinding strategies, control conditions or time points, and public sharing of raw data. PERSPECTIVE: We described the effects of several non-pharmacological manipulations on experimentally induced secondary hypersensitivity in humans. By shedding light on the potential for non-pharmacological therapies to influence secondary hypersensitivity, it opens a line of inquiry towards development and testing of targeted strategies for managing secondary hypersensitivity.