Pain Pathways in the Brain

Imaging Neural Mechanisms Underlying Pain Modulation

This study will evaluate brain pathways involved in feeling pain and pain relief following administration of pain medication. Magnetic resonance imaging (MRI) will be used to measure brain activity at sites that become more active following oral surgery and then to see if the activity changes after pain medication is administered. MRI combines a powerful magnet with an advanced computer system and radio waves to produce detailed pictures of organs and tissues. During the scan, the subject lies on a table in a narrow cylinder containing a magnetic field. He or she can speak with a staff member via an intercom system at all times during the procedure.

Healthy dental patients recruited through the NIH Clinical Research Volunteer Program may enroll in this study. Participants will undergo the following tests and procedures in two clinic visits:

Visit 1 - Sensitivity Testing

Participants are tested for sensitivity to warm and hot temperatures. A probe is applied to the skin (usually the forearm) and heated to temperatures ranging from room temperature to that of a hot cup of coffee. Participants rate the temperature using a scale ranging from "no pain" to the "worst pain imaginable" and rate the unpleasantness of the heat using a similar scale. The probe is applied up to 30 times, using random heat intensities. Participants are also asked compare the heat intensity to varying levels of sounds and to rate the magnitude of different sensations they have experienced in the past, such as the brightness of the sun and the loudness of a jet plane. A blood sample of about 2 ounces is also collected at this visit for DNA analysis to look for genes related to pain.

Visit 2 - Oral Surgery

Under local anesthetic, participants undergo extraction of their lower right wisdom tooth. After surgery, the patient is moved to the MRI scanner for brain imaging over 1-2 hours while the local anesthetic wears off. Patients may request a postoperative pain drug (Toradol) during the procedure, if needed. When the scan is complete, patients are dismissed from the clinic with additional pain medication (flurbiprofen) to use at home as directed.

Study Overview

• Status: Completed
• Conditions: Healthy; Tooth Extraction
• Intervention / Treatment: Procedure: MRI

Detailed Description

Functional neuroimaging provides a powerful tool for understanding how the brain may be involved in the perception of pain. It has made it possible to identify areas of the brain that are involved in the perception of experimental pain but very few studies have evaluated the sites in the brain that are activated during clinical pain and the effects of analgesic drugs. The proposed study will use the surgical removal of an impacted third molar as a model of acute clinical pain to identify sites that are activated following the offset of local anesthesia and to examine the effects of the NSAID analgesic ketorolac on attenuating sites that are activated as pain is relieved. Scans will be performed under non-pain baseline conditions, and again immediately following surgery as the local anesthetic wears off, clinical pain occurs, and following administration of the NSAID ketorolac. Differences among subjects in the amount of pain reported and brain activation will be compared to subjects' prior ratings of experimental pain and the presence of any genetic polymorphisms that are related to pain perception, inflammation, known pain pathways, or psychological factors related to pain. The findings from this research may help to reveal how pain is appreciated in the central nervous system, pharmacologically modified by NSAID analgesics and differs among individuals due to genetic factors.

• Study Type: Interventional
• Enrollment: 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institute of Dental and Craniofacial Research (NIDCR)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

ELIGIBILITY CRITERIA:

Subjects will be a convenience sample selected from the pool of 500 - 700 new patients screened annually for acute pain studies. Inclusion and Exclusion criteria will be applied to result in a homogeneous population of subjects with respect to the surgical difficulty of the tooth being extracted, a single lower right third molar.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: National Institute of Dental and Craniofacial Research (NIDCR)

Publications and helpful links

General Publications

• Apkarian AV, Krauss BR, Fredrickson BE, Szeverenyi NM. Imaging the pain of low back pain: functional magnetic resonance imaging in combination with monitoring subjective pain perception allows the study of clinical pain states. Neurosci Lett. 2001 Feb 16;299(1-2):57-60. doi: 10.1016/s0304-3940(01)01504-x.
• Bingel U, Quante M, Knab R, Bromm B, Weiller C, Buchel C. Subcortical structures involved in pain processing: evidence from single-trial fMRI. Pain. 2002 Sep;99(1-2):313-21. doi: 10.1016/s0304-3959(02)00157-4.
• Chen AC. New perspectives in EEG/MEG brain mapping and PET/fMRI neuroimaging of human pain. Int J Psychophysiol. 2001 Oct;42(2):147-59. doi: 10.1016/s0167-8760(01)00163-5.

Study record dates

Study Major Dates

• Study Start: February 1, 2004
• Study Completion: August 1, 2005

Study Registration Dates

• First Submitted: February 23, 2004
• First Submitted That Met QC Criteria: February 23, 2004
• First Posted (Estimate): February 24, 2004

Study Record Updates

• Last Update Posted (Estimate): March 4, 2008
• Last Update Submitted That Met QC Criteria: March 3, 2008
• Last Verified: August 1, 2005

More Information

Terms related to this study

• Keywords: MRI; Acute Pain; Wisdom Teeth; Third Molar Extraction; Third Molar Impaction; NSAID Analgesia; Pain Mechanisms; SNP's
• Other Study ID Numbers: 040125; 04-D-0125