Pupillometry as a Potential Objective Measurement of Pain Assessment in Healthy Volunteers.

Background

Pain leads to activation of the autonomic nervous system and thus, among other things, to pupillary reflex dilation (PRD). Previous studies have already confirmed a correlation between the perception of pain and the pupillary reaction, measured using pupillometry. However, the previous study populations were under the influence of medication for analgesia in perioperative setting or suffered from pain. This study examines the relationship between pupillary reaction and pain perception in healthy controls and addresses the question of whether endogenous pain inhibition, clinically tested by conditioned pain modulation (CPM), can be quantified using pupillometry.

Methods

Forty-two healthy volunteers (21 females, 21 males, mean age 27.9 ± 5.8 years, range 20-39 years) were included in this study. The PRD, as a measure of the pupillary reaction (variance from the base diameter in percent), was investigated during baseline, heat application and during CPM testing and results compared to the reported pain intensity on the numerical rating scale (NRS).

Results

The volunteers showed higher variances under painful conditions compared to the measurement at rest corresponding to higher sympathetic activity during pain. Volunteers with a higher variance, ie a stronger pupillary reaction, gave higher pain ratings than subjects with a lower pupil variance. However, there was no correlation between the NRS and PRD. PRD and pain ratings during CPM were significantly lower compared to heat pain application alone. However, there was no correlation between the calculated CPM effect and the PRD.

Conclusion

Pupillometry is capable of objectively reflecting the pain response, eg pain relief through CPM testing. However, the CPM effect calculated from the subjective pain ratings and the objective PRD measurements is not associated suggesting that both measure different aspects of pain perception. It must be discussed whether the CPM effect can be the correct measure for the functionality of the pain system.

Informations de copyright

© 2024 Krafthöfer et al.

Déclaration de conflit d'intérêts

Prof. Dr. Ralf Baron reports grants from EU Projects: “Europain“ (115007), DOLORisk (633491), IMI Paincare (777500), German Federal Ministry of Education and Research (BMBF): Verbundprojekt: Frühdetektion von Schmerzchronifizierung (NoChro) (13GW0338C), German Research Network on Neuropathic Pain (01EM0903), Pfizer Pharma GmbH, Grünenthal GmbH, Mundipharma Research GmbH und Co. KG., Alnylam Pharmaceuticals Inc., Zambon GmbH, Sanofi Aventis GmbH; personal fees from Pfizer Pharma GmbH, Sanofi Aventis GmbH, Grünenthal GmbH, Mundipharma, Lilly GmbH, Desitin Arzneimittel GmbH, Teva GmbH, Bayer AG, MSD GmbH, Seqirus Australia Pty. Ltd, Novartis Pharma GmbH, TAD Pharma GmbH, Grünenthal SA Portugal, Grünen¬thal Pharma AG Schweiz, Grünenthal B.V. Niederlande, Evapharma, Takeda Pharmaceuticals International AG Schweiz, Ology Medical Education Netherlands, Ever Pharma GmbH, Amicus Therapeutics GmbH, Novo Nordisk Pharma GmbH, Chiesi GmbH, Stada Mena DWC LLC Dubai, Hexal AG, Viatris, AstraZeneca GmbH, Sandoz, personal fees from Pfizer Pharma GmbH, Sanofi Aventis GmbH, Grünenthal GmbH, Lilly, Novartis Pharma GmbH, Bristol-Myers Squibb, Biogenidec, AstraZeneca GmbH, Daiichi Sankyo, Glenmark Pharmaceuticals S.A., Seqirus Australia Pty. Ltd, Teva Pharmaceuticals Europe Niederlande, Teva GmbH, Genentech, Mundipharma International Ltd. UK, Galapagos NV, Kyowa Kirin GmbH, Vertex Pharmaceuticals Inc., Biotest AG, Celgene GmbH, Desitin Arzneimittel GmbH, Regeneron Pharmaceuticals Inc. USA, Theranexus DSV CEA Frankreich, Abbott Products Operations AG Schweiz, Bayer AG, Grünenthal Pharma AG Schweiz, Akcea Therapeutics Germany GmbH, Asahi Kasei Pharma Corporation, AbbVie Deutschland GmbH & Co. KG, Air Liquide Sante International Frankreich, Alnylam Germany GmbH, Lateral Pharma Pty Ltd, Hexal AG, Angelini, Janssen, SIMR Biotech Pty Ltd Australien, Confo Therapeutics N. V. Belgium, Merz Pharmaceuticals GmbH, Neumentum Inc., F. Hoffmann-La Roche Ltd. Switzerland, AlgoTherapeutix SAS France, Nanobiotix SA France, AmacaThera Inc. Canada, Heat2Move, Resano GmbH, Esteve Pharmaceuticals SA, outside the submitted work. Prof. Dr. Janne Gierthmühlen reports personal fees, honorary and travel support from Grünenthal GmbH, personal fees for lecture from AbbVie, NeuroTech, Lundbeck, Lilly GmbH, MediSAGE, OmegaPharma; grants for research from Electro Zeutica, travel support from Novartis; personal fees, honorary for lecture from and advisory board of TEVA, outside the submitted work. The authors report no other conflicts of interest in this work.