Evidence map›Paper›PMID 39853871›Full record

ArticleEuropean journal of pain (London, England)2025

A Parallel Human and Rat Investigation of the Interaction Between Descending and Spinal Modulatory Mechanisms.

Anna Fieldwalker, Ryan Patel, Lucy Zhao, Mateusz W Kucharczyk, Michael Mansfield, Kirsty Bannister

Abstract read
In one paragraph

Article in European journal of pain (London, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Anna FieldwalkerMroue Fateh Centre for Pain Management, Great Ormond Street Hospital for Children, Guildford Street, London, UK.
Ryan PatelWolfson Sensory, Pain and Regeneration Centre, King's College London, Guy's Campus, London, UK.
Lucy ZhaoWolfson Sensory, Pain and Regeneration Centre, King's College London, Guy's Campus, London, UK.
Mateusz W KucharczykWolfson Sensory, Pain and Regeneration Centre, King's College London, Guy's Campus, London, UK.
Michael MansfieldSchool of Sport, Exercise and Rehabilitation Sciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham, UK.
Kirsty BannisterDepartment of Life Sciences, South Kensington, Imperial College London, London, UK.ORCID https://orcid.org/0000-0002-3043-3574

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHealthy individuals demonstrate considerable heterogeneity upon dynamic quantitative sensory testing assessment of endogenous pain modulatory mechanisms. For those who stratify into a 'pro-nociceptive profile' cohort, consisting of inefficient conditioned pain modulation (CPM) and elevated temporal summation of pain (TSP), the optimal approach for balancing the net output of pain modulatory processes towards anti-nociception remains unresolved. In this translational healthy human and rat study, we examined whether descending modulation countered spinal amplification during concurrent application of a CPM and TSP paradigm alongside pupillometry since pontine activity was previously linked to functionality of endogenous pain modulatory mechanisms and pupil dilation.

methodsPerceptual (quantitative sensory testing) and spinal neuronal (in vivo electrophysiology) assessment was performed in healthy humans and rats respectively upon application of parallel CPM/diffuse noxious inhibitory controls (cuff algometry) and TSP/wind-up (pinprick) paradigms alongside pupillometry.

resultsIn humans, repetitive pinprick stimulation produced TSP while concurrent application of a noxious conditioning stimulus did not affect pain ratings to a single pinprick stimulus, repetitive stimulation or the wind-up ratio. In rats, repetitive pinprick produced neuronal wind-up while concurrent application of a noxious conditioning stimulus inhibited neuronal responses to a single stimulus and repetitive stimulation but not the wind-up ratio. For pupillometry experiments, dilatory responses did not increase during application of a TSP or CPM paradigm in humans, while reliable rat responses were not obtained.

conclusionsUnder the conditions of our study, spinal amplification mechanisms surpassed descending inhibitory controls while pupillometry did not offer a reliable indicator of endogenous pain modulatory mechanism function. SIGNIFICANCE: In this translational healthy human and rat study, activity in descending inhibitory controls did not counter spinal amplification processes underpinned by wind up. Despite pupil dilation being previously linked to modulatory mechanisms, dilatory responses did not offer a reliable indicator of functionality. For pro-nociceptive individuals exhibiting inefficient conditioned pain modulation and/or high temporal summation of pain, dampening faciliatory mechanisms rather than augmenting top-down inhibitory processes may be a more effective pain-relief strategy.

Indexed as

Diffuse Noxious Inhibitory ControlNociceptionPainPain ThresholdSpinal CordAdultAnimalsFemaleHumansMalePain MeasurementPupilRatsRats, Sprague-DawleyYoung Adultconditioned pain modulationdiffuse noxious inhibitory controlsdorsal hornin vivo electrophysiologypupillometryquantitative sensory testingtemporal summation of painwide dynamic rangewind‐up

Identifiers

PMID39853871
PMCPMC11758248

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.