Dopamine Dependence of Offset Analgesia

Sponsor

Northwestern University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05669924

Collaborator

National Institute of Neurological Disorders and Stroke (NINDS) (NIH)

Enrollment

Location

Arms

8.4

Anticipated Duration (Months)

3.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Offset analgesia is a psychophysical phenomenon characterized by a transient, disproportionately large decrease in pain following a slight reduction in noxious stimulus intensity. This phenomenon is both mechanistically and clinically interesting. Mechanistically, it uncouples a noxious stimulus from pain qualia-two often-conflated constructs. Clinically, it is blunted in patients with chronic pain, making it a biomarker for chronic pain. Yet, we do not understand how offset analgesia occurs. By elucidating offset analgesia's mechanisms, we will gain a greater understanding of the nociceptive-pain circuitry. Moreover, it would transmute offset analgesia from a psychophysical correlate of chronic pain to a biomarker that provides neurophysiological insight. This project will investigate the dopaminergic basis of offset analgesia using fMRI and pharmacological perturbations.

The fMRI portion of this work will investigate the correlative role of nucleus accumbens in offset analgesia. If the mesolimbic system is responsible for offset analgesia, its dynamics should capture the temporal dissociation between the noxious stimulus (temperature) and pain ratings.

In the pharmacological portion of this work, we will administer methylphenidate or placebo (double-blinded, within-subject, crossover trial) to assess the effects of increased dopamine availability on offset analgesia's dynamics.

Condition or Disease	Intervention/Treatment	Phase
Pain	Drug: Methylphenidate Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Basic Science

Official Title:

The Neural Correlates of and Effects of Methylphenidate on Offset Analgesia

Actual Study Start Date :

Sep 19, 2022

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Methylphenidate	Drug: Methylphenidate 0.35 mg/kg methylphenidate will be administered after baseline testing and 45 min-1 hr before post-intervention testing.
Placebo Comparator: Placebo	Drug: Placebo Placebo for methylphenidate

Arm

Intervention/Treatment

Experimental: Methylphenidate

Drug: Methylphenidate

0.35 mg/kg methylphenidate will be administered after baseline testing and 45 min-1 hr before post-intervention testing.

Placebo Comparator: Placebo

Drug: Placebo

Placebo for methylphenidate

Outcome Measures

Primary Outcome Measures

Effect of methylphenidate on offset analgesia [6 months]
We will compare the dynamics of offset analgesia-i.e., the time series of pain visual analog scale ratings obtained while delivering a noxious stimulus that elicits offset analgesia-during the methylphenidate condition to that of the placebo condition.
Nucleus accumbens dynamics during offset analgesia [6 months]
We will regress the time course of nucleus accumbens BOLD activity onto the latent time series from our valence competition mode. In addition, we will regress the nucleus accumbens time course onto the pain VAS time course, which will allow our findings to be compared to standard analyses in the literature.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Exclusion Criteria:

Pregnant
History of chronic pain
History of neurological diagnosis
History of psychiatric diagnosis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern University	Chicago	Illinois	United States	60611

Sponsors and Collaborators

Northwestern University
National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

Principal Investigator: Andrew D Vigotsky, MS, Northwestern University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Andrew Vigotsky, PhD Candidate, Northwestern University

ClinicalTrials.gov Identifier:

NCT05669924

Other Study ID Numbers:

STU00213557
F31NS126012

First Posted:

Jan 3, 2023

Last Update Posted:

Jan 3, 2023

Last Verified:

Dec 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Keywords provided by Andrew Vigotsky, PhD Candidate, Northwestern University

Additional relevant MeSH terms:

Methylphenidate

Study Results

No Results Posted as of Jan 3, 2023