Are changes in nociceptive withdrawal reflex magnitude a viable central sensitization proxy? Implications of a replication attempt

Guekos, Alexandros; Grata, A.C.; Hubli, Michéle; Schubert, Mario; Schweinhardt, Petra

doi:10.1016/j.clinph.2022.09.011

Cited by 4 publications

(7 citation statements)

References 55 publications

(128 reference statements)

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“…The setup followed a previously published protocol where participants sat on a test bed, with the back rest inclined at 60°, their legs comfortably extended, and a towel placed below their knees. 43 …”

Section: Methodsmentioning

confidence: 99%

“…To that end, NWR-M is assessed before and after CS induction within the same dermatome where the induction paradigm was performed using repetitive NWR elicitations. 13 , 28 , 31 , 43 , 59 The procedure also allows to assess the NWR response rate (NWR-RR), ie, the percentage of obtained reflexes, which has recently been proposed as an objective CS proxy. 43 Studying changes in NWR-RR corresponds to indirectly testing for a modulation of the NWR threshold current, the minimum electrical current necessary to elicit a reflex response.…”

Section: Methodsmentioning

confidence: 99%

“…By definition, any meaningful change in threshold is also reflected in the NWR-RR, which either increases or decreases accordingly, because the number of elicited reflex responses correlates with the applied current with respect to threshold. 43 , 86 , 98 , 100 Assessing the NWR-RR thus yields the same information as separate threshold testing without the problem of the number of stimulations potentially differing across participants.…”

Section: Methodsmentioning

confidence: 99%

“…The stimulations were applied over the retromalleolar pathway of the sural nerve, and sEMG recordings were obtained from biceps femoris, rectus femoris, and tibialis anterior muscles according to a previously published protocol. 43 The recording window extended from 120 milliseconds prestimulation to 380 milliseconds poststimulation. Every electrical stimulation consisted of a train of 5 rectangular stimuli of 1-millisecond duration delivered at 200 Hz.…”

Section: Methodsmentioning

confidence: 99%

“… 36 , 77 Using both, Z and D as scoring criteria minimizes false classification of reflexes, which can be in the range of up to 5% because of contamination of the EMG traces by spontaneous muscle activation. 43 Furthermore, all traces were also visually inspected by the experimenters.…”

Section: Methodsmentioning

confidence: 99%

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Healthy women show more experimentally induced central sensitization compared with men

Guekos,

Saxer,

Salinas Gallegos

et al. 2024

Pain

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Women more often experience chronic pain conditions than men. Central sensitization (CS) is one key mechanism in chronic pain that can differ between the sexes. It is unknown whether CS processes are already more pronounced in healthy women than in men. In 66 subjects (33 women), a thermal CS induction protocol was applied to the dorsum of one foot and a sham protocol to the other. Spatial extent [cm2] of secondary mechanical hyperalgesia (SMH) and dynamic mechanical allodynia were assessed as subjective CS proxy measures, relying on verbal feedback. Changes in nociceptive withdrawal reflex magnitude (NWR-M) and response rate (NWR-RR) recorded through surface electromyography at the biceps and rectus femoris muscles were used as objective CS proxies. The effect of the CS induction protocol on SMH was higher in women than in men (effect size 2.11 vs 1.68). Nociceptive withdrawal reflex magnitude results were statistically meaningful for women (effect size 0.31-0.36) but not for men (effect size 0.12-0.29). Differences between men and women were not meaningful. Nociceptive withdrawal reflex response rate at the rectus femoris increased in women after CS induction and was statistically different from NWR-RR in men (median differences of 13.7 and 8.4% for 120 and 140% reflex threshold current). The objective CS proxy differences indicate that dorsal horn CS processes are more pronounced in healthy women. The even larger sex differences in subjective CS proxies potentially reflect greater supraspinal influence in women. This study shows that sex differences are present in experimentally induced CS in healthy subjects, which might contribute to women's vulnerability for chronic pain.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Healthy women show more experimentally induced central sensitization compared with men

Guekos,

Saxer,

Salinas Gallegos

et al. 2024

Pain

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Assessing signs of central sensitization: A critical review of physiological measures in experimentally induced secondary hyperalgesia

Leone,

Lenoir,

van den Broeke

2024

European Journal of Pain

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Background and ObjectivesCentral sensitization (CS) is believed to play a role in many chronic pain conditions. Direct non‐invasive recording from single nociceptive neurons is not feasible in humans, complicating CS establishment. This review discusses how secondary hyperalgesia (SHA), considered a manifestation of CS, affects physiological measures in healthy individuals and if these measures could indicate CS. It addresses controversies about heat sensitivity changes, the role of tactile afferents in mechanical hypersensitivity and detecting SHA through electrical stimuli. Additionally, it reviews the potential of neurophysiological measures to indicate CS presence.Databases and Data TreatmentFour databases, PubMed, ScienceDirect, Scopus and Cochrane Library, were searched using terms linked to ‘hyperalgesia’. The search was limited to research articles in English conducted in humans until 2023.ResultsEvidence for heat hyperalgesia in the SHA area is sparse and seems to depend on the experimental method used. Minimal or no involvement of tactile afferents in SHA was found. At the spinal level, the threshold of the nociceptive withdrawal reflex (RIII) is consistently reduced during experimentally induced SHA. The RIII area and the spinal somatosensory potential (N13‐SEP) amplitude are modulated only with long‐lasting nociceptive input. At the brain level, pinprick‐evoked potentials within the SHA area are increased.ConclusionsMechanical pinprick hyperalgesia is the most reliable behavioural readout for SHA, while the RIII threshold is the most sensitive neurophysiological readout. Due to scarce data on reliability, sensitivity and specificity, none of the revised neurophysiological methods is currently suitable for CS identification at the individual level.SignificanceGathering evidence for CS in humans is a crucial research focus, especially with the increasing interest in concepts such as ‘central sensitization‐like pain’ or ‘nociplastic pain’. This review clarifies which readouts, among the different behavioural and neurophysiological proxies tested in experimental settings, can be used to infer the presence of CS in humans.

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Replication attempts are important for the advancement of science even when they fail

Manresa

2023

Clinical Neurophysiology

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Are changes in nociceptive withdrawal reflex magnitude a viable central sensitization proxy? Implications of a replication attempt

Cited by 4 publications

References 55 publications

Healthy women show more experimentally induced central sensitization compared with men

Healthy women show more experimentally induced central sensitization compared with men

Assessing signs of central sensitization: A critical review of physiological measures in experimentally induced secondary hyperalgesia

Replication attempts are important for the advancement of science even when they fail

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