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Role of the Endogenous Opioid System Underlying Modulation of Experimental Pain

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01327326
Recruitment Status : Withdrawn
First Posted : April 1, 2011
Last Update Posted : July 13, 2012
American Pain Society
Information provided by (Responsible Party):
University of Florida

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.

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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

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: TMD patients


  • 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


  • 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

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.

Information from the National Library of Medicine

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

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01327326

Sponsors and Collaborators
University of Florida
American Pain Society
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Principal Investigator: Christopher D King, PhD University of Florida

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Responsible Party: University of Florida Identifier: NCT01327326     History of Changes
Other Study ID Numbers: APS2011
First Posted: April 1, 2011    Key Record Dates
Last Update Posted: July 13, 2012
Last Verified: July 2012
Keywords provided by University of Florida:
Pain modulation
Experimental pain
Additional relevant MeSH terms:
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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
Neurologic Manifestations
Signs and Symptoms
Alcohol Deterrents
Narcotic Antagonists
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents