Pain profiling in migraine: a systematic review of Quantitative Sensory Testing (QST), Conditioned Pain Modulation (CPM), and Corneal Confocal Microscopy (CCM)

Abstract

Objective: The aim of this systematic review is to identify pain profiling parameters that are reliably different between patients with migraine and healthy controls, using Quantitative Sensory Testing (QST) including Temporal Summation (TS), Conditioned Pain Modulation (CPM), and Corneal Confocal Microscopy (CCM).

Methods: A comprehensive literature search was conducted (up to 23 May 2024). The quality of the research was assessed using the Newcastle-Ottawa Scale (NOS) for non-randomized studies.

Results: Twenty-eight studies were included after screening. The QST studies indicate that migraine patients exhibit lower pressure pain thresholds (PPT), particularly in the trigeminal region. A previous meta-analysis reported lower heat pain thresholds (HPT). CPM studies suggest a (mild) inhibitory or absent response in migraine patients, not different from controls. High-frequency and chronic migraine patients may exhibit a facilitatory CPM response. With repeated executions of CPM, migraine patients display a diminishing CPM response, a phenomenon not observed in control subjects. CCM investigations in migraine patients revealed conflicting outcomes, likely as a result of small sample sizes and limited characterization of migraine features.

Conclusion: Pain profiling migraine patients varies due to sensory modality, applied methods, anatomical sites, and migraine features. Understanding pain profiling offers insights into migraine pathophysiology, requiring careful selection of parameters and differentiation among migraine subtypes.

Keywords: Allodynia; Chronic migraine (CM); Conditioned Pain Modulation (CPM); Corneal Confocal Microscopy (CCM); Episodic migraine (EM); Migraine; Pain profile; Psychophysical measure; Quantitative Sensory Testing (QST).

Fig. 1

Flowchart of the systematic literary screening. The search was performed on 23 May 2024. Exclusion criteria were:1) no full text availability; 2) not in English; 3) not in human study; 4) case report, meeting abstracts, editorials, commentaries, articles with a pediatric population (age < 18) or articles with incomplete information; 5) does not present own data with a prospective design; 6) did not enroll at least 1 migraine patient group that was not mixed with patients with other headache conditions (excluding MOH); 7) does not use 1 psychophysical measure (and QST published before January 2017); and 8) no baseline data available for all, or did not include a comparison with a control group for QST or CCM. QST = Quantitative Sensory Testing; CPM = Conditioned Pain Modulation; CCM = Corneal Confocal Microscopy

Fig. 2

Risk of Bias assessment from included studies. A) Traffic light plot per study with 1 = small sample size, 2 = self-reported measure of pain, 3 = self-diagnosed migraine, 4 = sample included possible medication overuse headache (MOH), 5 = no medication days/month reported, 6 = no headache or migraine days/month reported, 7 = incomplete patient characteristics, 8 = possible comorbidities not specified, 9 = migraine phase not specified and 10 = other bias. (B) Summary plot of risk of bias per subcategory. The Robvis tool was used to visualize the risk of bias assessment [31].