Slowly repeated evoked pain (SREP) as a central sensitization marker in episodic migraine patients

Pablo De La Coba,Stephen Bruehl,Gustavo A Reyes Del Paso

doi:10.1038/s41598-021-84157-1

Pablo De La Coba, Stephen Bruehl + Show 1 more

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https://doi.org/10.1038/s41598-021-84157-1

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Abstract

Migraine headache is a pain condition characterized by severe and recurrent unilateral head pain. Among other mechanisms, central pain sensitization processes seem to be involved in the disorder. An experimental protocol based on slowly repeated evoked pain (SREP) has been shown to indicate pain sensitization in fibromyalgia patients and differentiate these patients from healthy individuals and rheumatoid arthritis patients. This study examined SREP sensitization in migraine patients and explored its potential usefulness as a central sensitization marker. The SREP protocol was administered to 40 episodic migraine (EM) patients not currently experiencing a headache and 40 healthy controls. SREP consisted of a series of 9 suprathreshold painful pressure stimuli of 5 s duration and a 30 s interstimulus interval. SREP sensitization was indexed by the increase in pain ratings across the stimuli. Pain threshold, pain tolerance and temporal summation of pain were also assessed. SREP sensitization was observed in EM, but not in healthy individuals (p < .001). SREP differentiated between EM and healthy individuals with up to 75% diagnostic accuracy. Pain threshold, pain tolerance and temporal summation of pain did not show significant discriminative ability. An SREP index value of 0.5 was the most sensitive cut-off for detecting central pain sensitization when prioritizing diagnostic sensitivity (0.88). Results provide evidence for SREP as a possible central sensitization marker with potential clinical utility in migraine patients. Inclusion of SREP in Quantitative Sensory Testing protocols may enhance the assessment of altered pain modulation in different pain conditions.

Highlights

Migraine is a neuro-vascular disease characterized by severe, throbbing and recurrent unilateral pain
slowly repeated evoked pain (SREP) sensitization responses differed between groups, with SREP being observed in the episodic migraine (EM) group (SREP index > 0) but not in healthy participants (SREP index ≤ 0)
The present study tested the hypothesis that a dynamic evoked pain index based on application of slowly repeated evoked pain stimuli (SREP) might serve as a broad index of Central sensitization (CS) sensitization across a variety of pain conditions hypothesized to be CS-related, such as migraine headache, rather than being a specific clinical marker of fibromyalgia as might be suggested by previous SREP studies in the fibromyalgia population[34,50,51,61]

Summary

Introduction

Migraine is a neuro-vascular disease characterized by severe, throbbing and recurrent unilateral pain. Its underlying mechanisms are not yet fully understood[2] Both central and peripheral sensitization related to the activation of trigeminovascular neurons seem to be involved in the different pain components of m igraine[3]. The measurement of CS has been addressed in different ways, ranging from invasive methods used in animal pain models[12,13], to non-invasive methodologies used in human r esearch[14,15,16] These non-invasive CS measures include neuroimaging of responses to painful stimuli[16,17,18,19], evoked pain measures[20,21], and self-administered questionnaires assessing CS-related s ymptoms[22,23]. Both conditions have shown a notably greater prevalence in women than m en[46,47]

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