Pain Pathways in the Brain
Pain Pathways in the Brain
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.
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.
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.