Role of the Endogenous Opioid System Underlying Modulation of Experimental Pain

Study Description

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Brief Summary:

The aim of this proposal is to characterize pain inhibition in healthy controls and Temporomandibular Disorder (TMD) patients with two models of endogenous pain modulation (off-set analgesia; conditioned pain modulation), and to investigate the function of the endogenous opioid system in these responses by using pharmacological blockade of the opioid receptor.

Condition or disease	Intervention/treatment	Phase
Temporomandibular Disorder; Facial Pain	Drug: Naltrexone; Drug: Placebo	Not Applicable

Detailed Description:

Dysfunction in endogenous pain inhibitory systems has been proposed as a factor in the development and maintenance clinical pain disorders particularly in Temporomandibular Disorder (TMD). Dysfunction has been observed with a model known as diffuse noxious inhibitory controls (DNIC), but other models that engage inhibitory systems (offset analgesia) have not been fully evaluated in chronic pain patients.

DNIC evaluates an individual's capacity to engage endogenous pain inhibition. The paradigm is a spatial inhibition model based on the principle that "pain-inhibits-pain" in which pain in a local area is inhibited by a second pain that can be anywhere else in the body. DNIC is traditionally studied by observing a reduction of pain produced by a focal pain stimulus (contact heat) as a result of a second painful stimulus. Research from our lab and others suggests that pain inhibition is reduced in a number of chronic pain conditions. The investigators preliminary data suggests that pain inhibition during DNIC is modulated in part by endogenous opioids; however, results from other DNIC studies have been mixed. In addition, it is possible that reductions in the ability to engage endogenous inhibitory systems in chronic pain patients are due to a weakening of the endogenous opioid system. While pharmacological studies have been conducted with healthy cohorts, only one study has examined the opioid involvement in chronic pain patients.

Offset analgesia is thought to reflect a form of temporal pain inhibition which is usually defined by three stimulus temperature phases: a baseline phase followed by a manipulation phase in which the temperature is briefly increased and returns to the baseline temperature during an "offset" phase. A reduction in pain ratings is observed approximately 15s after the temperature drop (third phase), which is ~50% lower than ratings at the same time point for "constant" trials that continued 48°C for 40s. No studies have examined offset analgesia in a chronic pain cohort or its sensitivity of opioid blockade.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	0 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:	Basic Science
Official Title:	Opioid Modulation of Two Models of Pain Inhibition in Healthy Controls and Patients With Temporomandibular Disorder (TMD)
Study Start Date :	December 2011
Actual Primary Completion Date :	July 2012
Actual Study Completion Date :	July 2012

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: TMD patients; Intervention: Drug: Naltrexone; Drug: placebo	Drug: Naltrexone; Oral, 50 mg, 1 Time Dose; Other Name: Revia Drug: Placebo; Oral, 1 Time Dose; Other Name: Placebo/sugar pill
Active Comparator: Healthy controls; Intervention: Drug: Naltrexone; Drug: placebo	Drug: Naltrexone; Oral, 50 mg, 1 Time Dose; Other Name: Revia Drug: Placebo; Oral, 1 Time Dose; Other Name: Placebo/sugar pill

Outcome Measures

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Primary Outcome Measures :

1. Post-drug efficacy of pain inhibition [ Time Frame: 1 hour after study medication (day 1) ]
   A change in the ability to reduce experimental pain sensitivity during two models of pain inhibition will be evaluated before and after medication.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 50 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

• ages 18-50 years old
• Controls: pain-free based on Research Diagnostic Criteria (RDC) exam
• TMD: chronic musculoskeletal pain (face) based on Research Diagnostic Criteria (RDC) exam

Exclusion Criteria:

• Inability to adequately communicate and understand informed consent form;
• Inability to reliably rate pain intensity;
• Uncontrolled hypertension (or receiving treatment for hypertension with BP of greater than 140/95);
• Serious systemic (e.g. Diabetes, thyroid problems, etc.);
• Serious cardiovascular/pulmonary disease;
• Neurological problems with significant changes in somatosensory and pain perception at the intended stimulation sites (hand, foot);
• Serious psychiatric problems requiring treatment (schizophrenia, bipolar disorder);
• Other chronic pain conditions (e.g., low back pain, fibromyalgia);
• Any other ongoing acute pain problem (arthritis, injury-related pain); or,
• Irregular menstrual cycles (>40 days) or menstrual cycle disorders (e.g. PMS, dysmenorrhea).

Contacts and Locations

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Sponsors and Collaborators

University of Florida

American Pain Society

Investigators

Principal Investigator:	Christopher D King, PhD	University of Florida

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	University of Florida
ClinicalTrials.gov Identifier:	NCT01327326 History of Changes
Other Study ID Numbers:	APS2011
First Posted:	April 1, 2011
Last Update Posted:	July 13, 2012
Last Verified:	July 2012

Keywords provided by University of Florida:

Pain modulation; Experimental pain

Additional relevant MeSH terms:

Temporomandibular Joint Disorders; Temporomandibular Joint Dysfunction Syndrome; Facial Pain; Craniomandibular Disorders; Mandibular Diseases; Jaw Diseases; Musculoskeletal Diseases; Joint Diseases; Muscular Diseases; Stomatognathic Diseases	Myofascial Pain Syndromes; Pain; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Naltrexone; Narcotic Antagonists; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents