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

doi:10.1002/ejp.4775

journal article Open Access Jan 23, 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

European Journal of Pain Vol. 29 No. 3 · Wiley

View at Publisher Save 10.1002/ejp.4775

Abstract

ABSTRACTBackgroundHealthy 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.

Topics

No keywords indexed for this article. Browse by subject →

References

50

[1]

10.1097/j.pain.0000000000000240

[2]

10.1113/jphysiol.1987.sp016658

[3]

10.1111/j.1526-4610.2009.01545.x

[4]

10.1017/s0048577299970373

[5]

10.1097/j.pain.0000000000000331

[6]

10.1002/ejp.1580

[7]

10.1097/j.pain.0000000000001810

[8]

10.1016/j.pain.2003.09.005

[9]

10.1016/j.jneumeth.2017.01.005

[10]

10.11607/jop.943

[11]

10.1016/j.pain.2004.03.005

[12]

Who is healthy? Aspects to consider when including healthy volunteers in QST-based studies—a consensus statement by the EUROPAIN and NEUROPAIN consortia

Janne Gierthmühlen, Elena K. Enax-Krumova, Nadine Attal et al.

Pain 10.1097/j.pain.0000000000000227

[13]

Determinants of endogenous analgesia magnitude in a diffuse noxious inhibitory control (DNIC) paradigm: Do conditioning stimulus painfulness, gender and personality variables matter?

Michal Granot, Irit Weissman-Fogel, Yonathan Crispel et al.

Pain 10.1016/j.pain.2007.06.029

[14]

10.1097/j.pain.0000000000000294

[15]

10.1016/j.ejpain.2011.07.007

[16]

Wind-up of spinal cord neurones and pain sensation: much ado about something?

Juan F Herrero, Jennifer M.A Laird, Jose A Lopez-Garcia

Progress in Neurobiology 10.1016/s0301-0082(99)00051-9

[17]

10.1002/ejp.1408

[18]

10.1097/j.pain.0000000000001376

[19]

10.1002/ejp.2283

[20]

10.1080/08990220.2016.1229178

[21]

Relationships between Pupil Diameter and Neuronal Activity in the Locus Coeruleus, Colliculi, and Cingulate Cortex

Siddhartha Joshi, Yin Li, Rishi M. Kalwani et al.

Neuron 10.1016/j.neuron.2015.11.028

[22]

10.1016/j.jpain.2019.09.010

[23]

10.2147/jpr.s461906

[24]

Distinct brainstem to spinal cord noradrenergic pathways inversely regulate spinal neuronal activity

Mateusz W Kucharczyk, Francesca Di Domenico, Kirsty Bannister

Brain 10.1093/brain/awac085

[25]

A critical brainstem relay for mediation of diffuse noxious inhibitory controls

Mateusz W Kucharczyk, Francesca Di Domenico, Kirsty Bannister

Brain 10.1093/brain/awad002

[26]

10.3389/fncir.2018.00021

[27]

The effects of DNIC-type inhibition on temporal summation compared to single pulse processing: Does sex matter?

Stefan Lautenbacher, Miriam Kunz, Simone Burkhardt

Pain 10.1016/j.pain.2008.09.019

[28]

10.1016/0304-3959(79)90049-6

[29]

10.1523/eneuro.0122-21.2021

[30]

10.7554/elife.70510

[31]

10.1097/j.pain.0000000000001737

[32]

10.1097/j.pain.0000000000003217

[33]

10.1016/j.jpain.2005.01.352

[34]

10.1113/jp270294

[35]

10.1016/j.pain.2013.07.049

[36]

10.1097/j.pain.0000000000003166

[37]

10.1002/ejp.4741

[38]

The methodology of experimentally induced diffuse noxious inhibitory control (DNIC)-like effect in humans

Dorit Pud, Yelena Granovsky, David Yarnitsky

Pain 10.1016/j.pain.2009.02.015

[39]

10.1016/j.math.2015.02.011

[40]

Quantitative sensory testing: a comprehensive protocol for clinical trials

R. Rolke, W. Magerl, K. Andrews Campbell et al.

European Journal of Pain 10.1016/j.ejpain.2005.02.003

[41]

10.1016/0006-8993(85)91318-6

[42]

10.1016/s0304-3959(02)00325-1

[43]

10.1016/j.ejpain.2010.05.011

[44]

10.1016/j.neuron.2022.05.017

[45]

10.1097/j.pain.0000000000000543

[46]

Valiente C. D.2024.“Mechanisms of Cancer‐Induced Bone Pain in Rodent Models of Disease Progression and Regression.”Thesis (PhD). King's College London.

[47]

10.1371/journal.pone.0307556

[48]

10.1016/b978-0-12-374247-6.50019-5

[49]

World Medical Association Declaration of Helsinki

JAMA 10.1001/jama.2013.281053

[50]

Recommendations on practice of conditioned pain modulation (CPM) testing

D. Yarnitsky, D. Bouhassira, A.M. Drewes et al.

European Journal of Pain 10.1002/ejp.605

Metrics

6

Citations

50

References

Details

Published: Jan 23, 2025
Vol/Issue: 29(3)
License: View

Authors

A

Anna Fieldwalker

Mroue Fateh Centre for Pain Management Great Ormond Street Hospital for Children Guildford Street London UK

R

Ryan Patel

Wolfson Sensory, Pain and Regeneration Centre King's College London, Guy's Campus London UK

L

Lucy Zhao

Wolfson Sensory, Pain and Regeneration Centre King's College London, Guy's Campus London UK

M

Mateusz W. Kucharczyk

Wolfson Sensory, Pain and Regeneration Centre King's College London, Guy's Campus London UK

M

Michael Mansfield

School of Sport, Exercise and Rehabilitation Sciences, College of Life and Environmental Sciences University of Birmingham Birmingham UK

K

Kirsty Bannister

Department of Life Sciences South Kensington Imperial College London London UK

Cite This Article

Anna Fieldwalker, Ryan Patel, Lucy Zhao, et al. (2025). A Parallel Human and Rat Investigation of the Interaction Between Descending and Spinal Modulatory Mechanisms. European Journal of Pain, 29(3). https://doi.org/10.1002/ejp.4775

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

You May Also Like