Pain Modulation Effectiveness (PME)

NCT05783362 | Completed

• 1 other identifier: IRB202300187
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Conditioned pain modulation (CPM) is the behavioral measure of diffuse noxious inhibitory control (DNIC), an endogenous pain inhibitory pathway in which pain inhibits pain. Conditioned pain modulation is less efficient in individuals with chronic pain conditions, and it is a predictor for the development of chronic pain. Continuous stimulation of central/cortical mechanisms through engaging CPM might alter pain processing and improve pain inhibition. Healthy participants will be randomly assigned to one of three groups: High Exposure (HE), Low Exposure (LE), and No Exposure (NE). Pre-and post-intervention pain sensitivity including conditioned pain modulation will be assessed. The study will assess the central pain modulatory mechanisms (measured by CPM) that have differential changes in participants who receive high exposure CPM as an intervention from those who receive low or no exposure. The study will also assess the magnitude and efficiency of CPM contributing additional variance to a regression model predicting pain sensitivity after positive and negative affect, pain anxiety, and depression are considered in the model, establishing measures of central pain processing, like CPM, as unique contributors to pain intensity.

Conditions

Healthy People

Outcome Measures

Primary Outcomes (2)

• Conditioned Pain Modulation as an assessment

  Participants will receive a testing stimulus of pressure applied per ascending intensity at the web space of the foot until the pain reaches 40 out of 100, then discontinued. After testing the stimulus, Participants will receive a conditioning stimulus contact heat stimulus applied to the thenar of the left hand for 60 s at an intensity of 46.5 ◦C. Subjects will be asked to rate the heat pain during the four 60-second trials. Subjects will be instructed that they may remove their hand at any time if the heat is intolerable. After 60 seconds, the contact heat will be completely removed, and the testing stimulus will be re-applied to the web space of the dominant foot. Conditioned pain modulation will be calculated as the average pain ratings of the second testing stimulus series minus the average pain ratings of the first testing stimulus series. Negative numbers indicate efficient pain modulation

  Two weeks

• Expectations

  Individuals will be asked what they expect exposure to the coldpressor task to do the amount of pressure needed to generate pain (see "Intervention" for the coldpressor task).

  Two Weeks

Study Arms (3)

High Exposure (HE)

EXPERIMENTAL

Participants will receive five sessions total: four sessions of the Intervention, questionnaires, quantitative sensory testing, and CPM as an outcome in the first and fifth sessions.

Behavioral: Conditioned Pain Modulation (CPM)

Low Exposure (LE)

EXPERIMENTAL

Participants will receive only two sessions in total: questionnaires, quantitative sensory testing, and CPM as an outcome at both sessions.

Behavioral: Conditioned Pain Modulation (CPM)

No Exposure (NE)

NO INTERVENTION

This group controls for natural history response, and participants will receive two sessions of questionnaires, and CPM as an outcome, and quantitative sensory testing for one session (last session).

Interventions

Conditioned Pain Modulation (CPM) BEHAVIORAL

Participants will receive a testing stimulus of pressure applied per ascending intensity at the web space of the foot until the pain reaches 40 out of 100, then discontinued. After testing the stimulus, participants will then receive a conditioning stimulus by immersing the non-dominant hand into the water-cooled by refrigeration unit with a temperature of 6 degree Celsius (males) or 8 degree Celsius (females) for 60 seconds. Subjects will be asked to rate the cold pain during the four 60-second trials. Participants completely removed their hand from the cold pressor for 30 seconds following each of the four 60-second immersions, during which time the testing stimulus will be re-applied per the sequential paradigm to the web space of the foot. Participants complete four 60-second periods of immersion. Conditioned pain modulation will be calculated as the average pain ratings of the second testing stimulus series minus the average pain ratings of the first testing stimulus series.

High Exposure (HE); Low Exposure (LE)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Not currently seeking treatment for pain past month;
• between 18 - 75 years old.

You may not qualify if:

• non-English speaking;
• systemic medical condition is known to affect sensation (i.e., diabetes);
• regular use of prescription pain medication to manage pain;
• current or history of chronic pain condition;
• currently using blood thinning medication;
• any blood clotting disorder such as hemophilia;
• any contraindication to the application of ice or cold packs, such as uncontrolled hypertension, cold urticaria, cryoglobulinemia, paroxysmal cold hemoglobinuria, and circulatory compromise;
• involved in vigorous physical activities like heavy lifting, digging, aerobics or fast bicycling.

Sponsors & Collaborators

• University of Florida: lead

Study Sites (1)

University of Florida

Gainesville, Florida, 32608, United States

Location

Related Publications (16)

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  PMID: 24010588 BACKGROUND

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  PMID: 30146050 BACKGROUND

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• Goubert D, Danneels L, Cagnie B, Van Oosterwijck J, Kolba K, Noyez H, Meeus M. Effect of Pain Induction or Pain Reduction on Conditioned Pain Modulation in Adults: A Systematic Review. Pain Pract. 2015 Nov;15(8):765-77. doi: 10.1111/papr.12241. Epub 2014 Nov 11.

  PMID: 25387406 BACKGROUND

• Ibancos-Losada MDR, Osuna-Perez MC, Castellote-Caballero MY, Diaz-Fernandez A. Conditioned Pain Modulation Effectiveness: An Experimental Study Comparing Test Paradigms and Analyzing Potential Predictors in a Healthy Population. Brain Sci. 2020 Aug 30;10(9):599. doi: 10.3390/brainsci10090599.

  PMID: 32872642 BACKGROUND

• Kennedy J, Roll JM, Schraudner T, Murphy S, McPherson S. Prevalence of persistent pain in the U.S. adult population: new data from the 2010 national health interview survey. J Pain. 2014 Oct;15(10):979-84. doi: 10.1016/j.jpain.2014.05.009.

  PMID: 25267013 BACKGROUND

• Kosek E, Ordeberg G. Abnormalities of somatosensory perception in patients with painful osteoarthritis normalize following successful treatment. Eur J Pain. 2000;4(3):229-38. doi: 10.1053/eujp.2000.0175.

  PMID: 10985866 BACKGROUND

• Nir RR, Granovsky Y, Yarnitsky D, Sprecher E, Granot M. A psychophysical study of endogenous analgesia: the role of the conditioning pain in the induction and magnitude of conditioned pain modulation. Eur J Pain. 2011 May;15(5):491-7. doi: 10.1016/j.ejpain.2010.10.001. Epub 2010 Oct 28.

  PMID: 21035364 BACKGROUND

• Nir RR, Yarnitsky D. Conditioned pain modulation. Curr Opin Support Palliat Care. 2015 Jun;9(2):131-7. doi: 10.1097/SPC.0000000000000126.

  PMID: 25699686 BACKGROUND

• Pud D, Granovsky Y, Yarnitsky D. The methodology of experimentally induced diffuse noxious inhibitory control (DNIC)-like effect in humans. Pain. 2009 Jul;144(1-2):16-9. doi: 10.1016/j.pain.2009.02.015. Epub 2009 Apr 8. No abstract available.

  PMID: 19359095 BACKGROUND

• Yarnitsky D. Conditioned pain modulation (the diffuse noxious inhibitory control-like effect): its relevance for acute and chronic pain states. Curr Opin Anaesthesiol. 2010 Oct;23(5):611-5. doi: 10.1097/ACO.0b013e32833c348b.

  PMID: 20543676 BACKGROUND

• Yarnitsky D, Bouhassira D, Drewes AM, Fillingim RB, Granot M, Hansson P, Landau R, Marchand S, Matre D, Nilsen KB, Stubhaug A, Treede RD, Wilder-Smith OH. Recommendations on practice of conditioned pain modulation (CPM) testing. Eur J Pain. 2015 Jul;19(6):805-6. doi: 10.1002/ejp.605. Epub 2014 Oct 20.

  PMID: 25330039 BACKGROUND

• Yarnitsky D, Granot M, Nahman-Averbuch H, Khamaisi M, Granovsky Y. Conditioned pain modulation predicts duloxetine efficacy in painful diabetic neuropathy. Pain. 2012 Jun;153(6):1193-1198. doi: 10.1016/j.pain.2012.02.021. Epub 2012 Apr 3.

  PMID: 22480803 BACKGROUND

• 15. Souvlis, T., Vicenzino, B., and Wright. A. (2004). Neurophysiological effect of spinal manual therapy. Grieve's Modern Manual Therapy: The Vertebral Column. Edited by Jeffrey D. Boyling and Gwendolen A. Jull. Edinburgh, United Kingdom: Churchill Livingstone.367-380.

  BACKGROUND

• Rana P, Robinson ME, Alappattu MJ, Riley Iii J, Lott D, Bishop MD. Impact of repeated exposure to CPM on CPM efficiency and pain sensitivity in healthy adults: a randomized controlled trial. Front Pain Res (Lausanne). 2025 Nov 13;6:1677563. doi: 10.3389/fpain.2025.1677563. eCollection 2025.

  PMID: 41322117 DERIVED

Study Officials

• Mark Bishop, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Individuals will be randomized to one of three groups: High Exposure (HE), Low Exposure (LE), No Exposure (NE).

Study Record Dates

• First Submitted: March 13, 2023
• First Posted: March 24, 2023
• Study Start: April 1, 2023
• Primary Completion: June 25, 2023
• Study Completion: August 25, 2023
• Last Updated: August 31, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)