Automated Nociceptive Withdrawal Reflex Measurements Reveal Normal Reflex Thresholds and Augmented Pain Ratings in Patients with Fibromyalgia

Abstract

The nociceptive withdrawal reflex (NWR) is used to probe spinal cord excitability in chronic pain states. Here, we used an automated and unbiased procedure for determining the NWR threshold and compared the reflex thresholds and corresponding pain ratings in a well-characterized cohort of fibromyalgia (n = 29) and matched healthy controls (n = 21). Surface electrical stimuli were delivered to the foot in a stepwise incremental and decremental manner. The surface electromyographic activity was recorded from the ipsilateral tibialis anterior muscle. Fibromyalgia patients reported significantly higher scores for psychological distress and pain-related disability and a significantly lower score for perceived state of health compared to the matched controls. The subjective pain ratings were significantly higher in patients. The NWR thresholds were similar to the controls. In the patients, but not in controls, the NWR thresholds and subjective pain ratings were significantly correlated. Our results showed an increased subjective pain sensitivity in fibromyalgia, but we found no evidence for spinal sensitization based on the reflex measures.

Investigations into an overlooked early component of painful nociceptive withdrawal reflex responses in humans

“…In terms of RII-III prevalence, 192 (50.3%) reflex responses were identified in the 90-to 150-ms latency range corresponding to RIII, and 190 reflexes (49.7%) were identified in the 50-to 90-ms latency range corresponding to RII. The RII data are new: the pre-set 90-ms latency cut-off implemented in Ydrefors et al (2020) resulted in an automatic discounting of shorter latency responses. To compare pain with NWR responses, only those reflex responses that were painful (at least a 4 rating on a 0-10 scale) were included in the main analysis.…”

“…In Ydrefors et al (2020), an automated method was used to detect reflex responses with Z-scores of ≥12. Here, visual inspection of the data allowed us to include responses with Z-scores ≥6.…”

“…In Ydrefors et al (2020), a Z-score of ≥12 was considered a successful muscle response. In that study, a fully automated method was used for NWR detection, therefore the Z-score had to be large enough to ensure that noise would not be interpreted as muscle response.…”

“…NWR responses and pain ratings were successfully extracted for 20 fibromyalgia patients (FM: age range, all female) and 10 healthy controls (HC: age range, all female). For details on patient eligibility criteria, refer to Ydrefors et al (2020). Raw data were unavailable for 10 HC and therefore another 10 HC were recruited (18-30 years, all female).…”

“…Using microneurography, we recently showed that humans, akin to other mammals, are equipped with ultrafast (Aβ range) nociceptors in the skin (Nagi et al 2019). Considering this finding, we revisited our earlier work on NWR measurements (Ydrefors et al 2020): in that study, following convention, NWR responses were only selected if they occurred ≥90 ms, consistent with the presumed Ad-fiber range. Here we expanded the time window to search for shorter latency responses with the hypothesis that those are nociceptive, corresponding to painful sensations.…”