The nociceptive flexion reflex: a scoping review and proposed standardized methodology for acquisition in those affected by chronic pain

The nociceptive flexion reflex (NFR) is used in neurophysiological research as an objective measure of nociception. NFR thresholds are reduced in numerous chronic pain pathologies, which are indicative of common central hyperexcitability within conditions. However, variation exists in both the NFR assessment and determinants of NFR threshold among research groups. Our purpose was to provide a review of the recent literature to (a) confirm the NFR threshold's efficacy in identifying those with chronic pain compared to controls and (b) provide a narrative synthesis on the current methodology used to assess the NFR in clinical populations. We conducted a review of multiple databases (MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Google Scholar and Cochrane Library), including articles that reported controlled clinical studies of humans, in English, comparing NFR thresholds within chronic pain conditions to matched control subjects, published since the last NFR review in 2010. Our search resulted in nine studies included in our narrative synthesis and eight studies included in a meta-analysis. There was a significant pooled standardized mean difference in NFR threshold between chronic pain conditions and controls (-0.94, 95% confidence interval (CI) -1.33 to -0.55, p < 0.0001), with substantial heterogeneity of pooled estimates (I ² = 87%, τ ² = 0.41, Q = 76.13, the degrees of freedom (df) = 11, p < 0.0001). Significant variations in participant positioning, stimulation parameters and determinants of the NFR threshold were evident among included studies. We provided a narrative synthesis on the methodologies of included studies, as a recommendation for future studies in the assessment of the NFR in chronic pain.