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. 2020 Nov;24(10):2015-2026.
doi: 10.1002/ejp.1645. Epub 2020 Sep 22.

Pain-autonomic interaction: A surrogate marker of central sensitization

Paulina S Scheuren  1 , Jan Rosner  1   2 , Armin Curt  1 , Michèle Hubli  1
Affiliations

Pain-autonomic interaction: A surrogate marker of central sensitization

Paulina S Scheuren et al. Eur J Pain. 2020 Nov.

Abstract

Background: Central sensitization represents a key pathophysiological mechanism underlying the development of neuropathic pain, often manifested clinically as mechanical allodynia and hyperalgesia. Adopting a mechanism-based treatment approach relies highly on the ability to assess the presence of central sensitization. The aim of the study was to investigate potential pain-autonomic readouts to operationalize experimentally induced central sensitization in the area of secondary hyperalgesia.

Methods: Pinprick evoked potentials (PEPs) and sympathetic skin responses (SSRs) were recorded in 20 healthy individuals. Three blocks of PEP and SSR recordings were performed before and after heat-induced secondary hyperalgesia. All measurements were also performed before and after a control condition. Multivariate analyses were performed using linear mixed-effect regression models to examine the effect of experimentally induced central sensitization on PEP and SSR parameters (i.e. amplitudes, latencies and habituation) and on pinprick pain ratings.

Results: The noxious heat stimulation induced robust mechanical hyperalgesia with a significant increase in PEP and SSR amplitudes (p < 0.001) in the area of secondary hyperalgesia. Furthermore, PEP and SSR habituation were reduced (p < 0.001) after experimentally induced central sensitization.

Conclusions: The findings demonstrate that combined recordings of PEPs and SSRs are sensitive to objectify experimentally induced central sensitization and may have a great potential to reveal its presence in clinical pain conditions. Corroborating current pain phenotyping with pain-autonomic markers has the potential to unravel central sensitization along the nociceptive neuraxis and might provide a framework for mechanistically founded therapies.

Significance: Our findings provide evidence that combined recordings of sympathetic skin responses (SSRs) and pinprick evoked potentials (PEPs) might be able to unmask central sensitization induced through a well-established experimental pain model in healthy individuals. As such, these novel readouts of central sensitization might attain new insights towards complementing clinical pain phenotyping.

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