Pain‐autonomic interaction: A surrogate marker of central sensitization

Scheuren, Paulina Simonne; Rösner, Jan; Curt, Armin; Hubli, Michéle

doi:10.1002/ejp.1645

Cited by 22 publications

(35 citation statements)

References 57 publications

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“…In experimental pain assessment, the pain response is often recorded via different output channels, because these are not necessarily consistent within an individual (Cowen et al, 2015; Scheuren et al, 2020). Thus, in addition to subjective self‐report of pain, other more objectively measurable methods, such as electrodermal activity (EDA) as a proxy for autonomic nervous system (ANS) dynamics (Posada‐Quintero & Chon, 2020), are integrated.…”

Section: Introductionmentioning

confidence: 99%

Temporal properties of pain contrast enhancement using repetitive stimulation

Szikszay

Adamczyk

Lévénez

et al. 2022

European Journal of Pain

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Background Offset analgesia (OA) is characterized by a disproportionately large reduction in pain following a small decrease in noxious stimulation and is based on temporal pain contrast enhancement (TPCE). The underlying mechanisms of this phenomenon are still poorly understood. This study is aiming to investigate whether TPCE can also be induced by repetitive stimulation, i.e., by stimuli clearly separated in time. Methods A repetitive TPCE paradigm was induced in healthy, pain‐free subjects (n = 33) using heat stimuli. Three different interstimulus intervals (ISIs) were used: 5, 15, and 25 s. All paradigms were contrasted with a control paradigm without temperature change. Participants continuously rated perceived pain intensity. In addition, electrodermal activity (EDA) was recorded as a surrogate measure of autonomic arousal. Results Temporal pain contrast enhancement was confirmed for ISI 5 s (p < 0.001) and ISI 15 s (p = 0.005) but not for ISI 25 s (p = 0.07), however, the magnitude of TPCE did not differ between ISIs (p = 0.11). A TPCE‐like effect was also detected with increased EDA values. Conclusions TPCE can be induced by repetitive stimulation. This finding may be explained by a combination of the mechanisms underlying the OA and a facilitated pain habituation. Significance This experiment shows for the first time that temporal contrast enhancement of pain can be elicited by stimuli that are clearly separated in time with an interstimulus interval below 25 s.

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Section: Introductionmentioning

confidence: 99%

Temporal properties of pain contrast enhancement using repetitive stimulation

Szikszay

Adamczyk

Lévénez

et al. 2022

European Journal of Pain

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“…Central sensitization, an important feature of migraine, 47 has recently been demonstrated in patients with POTS (both with and without migraine) and may be a significant shared pathophysiology 48 . Central sensitization in POTS and migraine may involve elevations in pro‐inflammatory cytokines 47,49 as well as interactions between pain and autonomic circuitry 50 …”

Section: Migraine and Pots Pathophysiologymentioning

confidence: 99%

“…48 Central sensitization in POTS and migraine may involve elevations in pro-inflammatory cytokines 47,49 as well as interactions between pain and autonomic circuitry. 50 As discussed in section 2.0, post-ganglionic sympathetic denervation and augmented activity of the sympatho-adrenal medullary axis contribute to the development of neurogenic and hyperadrenergic POTS, respectively. There is emerging evidence that similar pathology exists in people with migraine.…”

Section: Pathophysiology In Pots and Migrainementioning

confidence: 99%

Postural orthostatic tachycardia syndrome and migraine: A narrative review

Mueller

Robinson‐Papp

2022

Headache

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Objective In this narrative review, we summarize experimental and clinical evidence demonstrating mechanistic connections between POTS and migraine. Background Migraine is the most common comorbidity in patients with POTS, a heterogenous disorder of the autonomic nervous system characterized by orthostatic intolerance and positional tachycardia. POTS is a debilitating illness with few effective treatments. We aim for this narrative review to increase awareness of the mechanistic connections between POTS and migraine providing foundational information that optimizes clinical care and advances the development of pathophysiologic‐based treatments. Methods We used the PubMed and Medline databases in November 2021 to perform a literature review and searched for the following keywords: “postural orthostatic tachycardia syndrome,” “POTS,” “autonomic nervous system,” AND “migraine,” “headache.” Results The high prevalence of migraine in patients with POTS may be explained by common pathologic mechanisms. There is evidence that dysregulation of the sympathetic nervous system, alterations in central and peripheral hemodynamics, and central sensitization increase vulnerability to both POTS and migraine. Non‐pharmacologic and pharmacologic treatments that target these shared mechanisms may provide significant benefit for the patient with POTS and migraine. Conclusions Identification of common affected pathways may provide important insight that advances our understanding and treatment of both migraine and POTS.

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“…In SCI, the assessment of TSP has been performed using repetitive phasic (Defrin et al, 2001;Eide et al, 1996;Konopka et al, 2012) and tonic (Albu et al, 2015;Gruener et al, 2016;Scheuren et al, 2019) noxious stimuli. Generally, studies found a higher occurrence and magnitude of TSP in subjects with SCI with NP (SCI-NP) compared to those without (SCI-nonNP) and healthy controls (HC) (Defrin et al, 2001;Gruener et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…Common denominators are an initial decrease of pain rating, i.e. adaptation (Gruener et al, 2016;Scheuren et al, 2019), followed by a subsequent increase, i.e. TSP, the latter potentially reflecting spinal sensitization, i.e.…”

Section: Introductionmentioning

confidence: 99%

Indicators of central sensitization in chronic neuropathic pain after spinal cord injury

Lütolf

Rösner

Curt

et al. 2022

European Journal of Pain

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Background Central sensitization is considered a key mechanism underlying neuropathic pain (NP) after spinal cord injury (SCI). Methods Two novel proxies for central sensitization were investigated in thoracic SCI subjects with (SCI‐NP) and without NP (SCI‐nonNP) compared to healthy controls (HC). Specifically, temporal summation of pain (TSP) was investigated by examining pain ratings during a 2‐min tonic heat application to the volar forearm. Additionally, palmar heat‐induced sympathetic skin responses (SSR) were recorded in order to reveal changes in pain‐autonomic interaction above the lesion level. Pain extent was assessed as the percentage of the body area and the number of body regions being affected by NP. Results Enhanced TSP was observed in SCI‐NP (+66%) compared to SCI‐nonNP (−75%, p = 0.009) and HC (−59%, p = 0.021). In contrast, no group differences were found (p = 0.685) for SSR habituation. However, pain extent in SCI‐NP was positively correlated with deficient SSR habituation (body area: r = 0.561, p = 0.024; body regions: r = 0.564, p = 0.023). Conclusions These results support the value of TSP and heat‐induced SSRs as proxies for central sensitization in widespread neuropathic pain syndromes after SCI. Measures of pain‐autonomic interaction emerged as a promising tool for the objective investigation of sensitized neuronal states in chronic pain conditions. Significance We present two surrogate readouts for central sensitization in neuropathic pain following SCI. On the one hand, temporal summation of tonic heat pain is enhanced in subjects with neuropathic pain. On the other hand, pain‐autonomic interaction reveals potential advanced measures in chronic pain, as subjects with a high extent of neuropathic pain showed diminished habituation of pain‐induced sympathetic measures. A possible implication for clinical practice is constituted by an improved assessment of neuronal hyperexcitability potentially enabling mechanism‐based treatment.

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Pain‐autonomic interaction: A surrogate marker of central sensitization

Cited by 22 publications

References 57 publications

Temporal properties of pain contrast enhancement using repetitive stimulation

Temporal properties of pain contrast enhancement using repetitive stimulation

Postural orthostatic tachycardia syndrome and migraine: A narrative review

Indicators of central sensitization in chronic neuropathic pain after spinal cord injury

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