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. 2024 Mar 13:17:989-1003.
doi: 10.2147/JPR.S436645. eCollection 2024.

Contact-Heat Evoked Potentials: Insights into Pain Processing in CRPS Type I

Florin Allmendinger  1 , Paulina Simonne Scheuren  1   2   3   4 , Iara De Schoenmacker  1 , Florian Brunner  5 , Jan Rosner  1   2   6 , Armin Curt  1 , Michèle Hubli  1
Affiliations

Contact-Heat Evoked Potentials: Insights into Pain Processing in CRPS Type I

Florin Allmendinger et al. J Pain Res. .

Abstract

Purpose: The pathophysiological mechanisms underlying the development of chronic pain in complex regional pain syndrome (CRPS) are diverse and involve both peripheral and central changes in pain processing, such as sensitization of the nociceptive system. The aim of this study was to objectively distinguish the specific changes occurring at both peripheral and central levels in nociceptive processing in individuals with chronic CRPS type I.

Patients and methods: Nineteen individuals with chronic CRPS type I and 16 age- and sex-matched healthy controls (HC) were recruited. All individuals underwent a clinical examination and pain assessment in the most painful limb, the contralateral limb, and a pain-free control area to distinguish between peripheral and central mechanisms. Contact-heat evoked potentials (CHEPs) were recorded after heat stimulation of the three different areas and amplitudes and latencies were analyzed. Additionally, quantitative sensory testing (QST) was performed in all three areas.

Results: Compared to HC, CHEP amplitudes in CRPS were only increased after stimulation of the painful area (p=0.025), while no increases were observed for the pain-free control area (p=0.14). None of the CHEP latencies were different between the two cohorts (all p>0.23). Furthermore, individuals with CRPS showed higher pain ratings after stimulation of the painful limb compared to their contralateral limb (p=0.013). Lastly, compared to HC, mechanical (p=0.012) and thermal (p=0.046) sensitivity was higher in the painful area of the CRPS cohort.

Conclusion: This study provides neurophysiological evidence supporting an intact thermo-nociceptive pathway with signs of peripheral sensitization, such as hyperexcitable primary afferent nociceptors, in individuals with CRPS type I. This is further supported by the observation of mechanical and thermal gain of sensation only in the painful limb. Additionally, the increased CHEP amplitudes might be related to fear-induced alterations of nociceptive processing.

Keywords: complex regional pain syndrome; contact-heat evoked potentials; pain hypersensitivity; pain mechanism; sensitization; thermo-nociceptive processing.

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Conflict of interest statement

The authors declare no conflicts of interest in this work.

Figures

Figure 1
Figure 1
CHEP latencies. Normalized CHEP N2-latencies showing deviation in percentage from the reference data, where the dotted line represents the mean of the reference data. Normalized N2-latencies are shown after stimulation of the painful, the contralateral and the remote, control area in the cohorts of CRPS and HC.
Figure 2
Figure 2
Representative examples of contact heat evoked potentials (CHEPs) of an individual with CRPS (red) and an age- and sex-matched HC (blue) stimulated in the painful area. Vertical dashed lines mark the N2- and P2-peak. (A) CHEPs (average and single trials) from a CRPS individual (f, 57y, tested area: hand). (B) CHEPs (average and single trials) from a HC individual (f, 52y, tested area: hand). (C) Overlay of the two averaged CHEPs from both individuals.
Figure 3
Figure 3
CHEP amplitudes. Normalized CHEP N2P2-amplitudes showing deviation in percentage from the reference data, where the dotted line represents the mean of the reference data. Normalized N2P2-amplitudes are shown after stimulation of the painful, the contralateral and the remote, control area in the cohorts of CRPS and HC. *p < 0.05.
Figure 4
Figure 4
Heat pain ratings. Normalized pain ratings showing deviation in percentage from the reference data, where the dotted line represents the mean of the reference data. Normalized pain ratings are shown after stimulation of the painful, the contralateral and the remote, control area in the cohorts of CRPS and HC. *p < 0.05.
Figure 5
Figure 5
QST z-scores of heat pain threshold (HPT), mechanical pain threshold (MPT) and mechanical pain sensitivity (MPS) of the painful, the contralateral and the control area in the cohorts of CRPS (red) and HC (blue). *p < 0.05. ***p < 0.001.
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