This study will test the effectiveness of the drug capsaicin in controlling pain after third
molar (wisdom tooth) extraction. Capsaicin, the ingredient in chili peppers that makes them
"hot," belongs to a class of drugs called vanilloids, which have been found to temporarily
inactivate pain-sensing nerves.
Healthy normal volunteers between 16 and 40 years of age who require third molar (wisdom
tooth) extraction may be eligible for this study. Participants will undergo the following
procedures in three visits:
Patients will have touch (sensory) testing by the following three methods: 1) a warm sensor
applied to the gums and the patient will rate when they first feel heat and when the heat
feels painful; 2) the bristles of a small paint brush will be gently stroked across the
gums, and the patient will say whether it feels painful; 3) a light touch will be applied to
the gums with a small needle, and the patient will rate the pain intensity following the
After testing, patients will be numbed with a local anesthetic (bupivacaine) and then
capsaicin or placebo (an inactive solution) will be injected next to the tooth. The tooth
then will be extracted one day later.
Patients will return to the clinic after 24 hours to repeat the same type of sensory
testing. After testing, patients will be sedated and numbed with a local anesthetic
(lidocaine) and given an intravenous injection of either saline or ketorolac (30 mg). After
the extraction, pain ratings will be recorded every 20 minutes, for up to 6 hours. During
this time, patients will be monitored for numbness, pain, side effects and vital signs
(heart rate, blood pressure, respiration, etc.). Those who request pain medicine will
receive acetaminophen and codeine. Patients will be required to stay for up to 3 more hours
after this and then they will then be discharged with pain medicine.
Patients will return to the clinic after another 48 hours to repeat the same sensory
testing. Remaining wisdom teeth will be removed "off-study" at least three weeks following
the first visit.
Successful preemptive analgesia strategies are superior to traditional pain management
schemes in the management of post-operative pain. However, agents with appropriate
pharmacokinetic properties are not readily available. The premise of this double-blind,
placebo and positive-controlled clinical study is to evaluate the efficacy of vanilloid
agonists as preemptive agents in an oral surgery tissue injury model. Vanilloids are a
class of small organic compounds; the most familiar of which is capsaicin, the active
ingredient in hot pepper. Binding of capsaicin to the vanilloid-1 receptor produces initial
activation and then long-acting desensitization of pain specific neurons. We propose to
produce a selective, long-term inactivation of peripheral pain transmission through the
local application of capsaicin in the oral mucosa in an effort to prevent or reduce
post-operative pain in the oral surgery model. Healthy subjects will be recruited, and
following local anesthesia, will be given an intramucosal injection of either capsaicin or
placebo. (Or as a positive control, 24 hours later, intravenous Toradol). Subjects will
have one lower impacted wisdom tooth extracted under local anesthesia and then will rate
their pain. The time of analgesic rescue medication request will be noted. A decrease in
post-operative pain and decrease in analgesic use will be taken as a positive effect of the
vanilloid for decreasing post-operative pain. We anticipate that through the long term
blockade of pain specific fibers pre-operatively that there will be a significant
attenuation of post-operative pain development following surgery. This has significant
implications for reducing pain and suffering, decreasing analgesic use, and reducing
post-operative complications following surgery.
Male or female volunteers referred for mandibular third molar extraction with a minimal
difficulty rating score of 3-4; the rating will be verified by the oral surgeon at time of
Age between 16-40.
ASA status 1 or 2, deemed in good general health (able to tolerate outpatient conscious
Willing to return at 24 hours for extraction of 1 tooth and be willing to wait up to 6
hours for post op observation following tooth extraction.
Willing to return another 48 hours later for final sensory testing.
ASA status 3-5 and Emergency operation (E) that do not get a physician clearance; i.e.
systemic disturbances that limits the patient's activity.
Pregnant or breast-feeding mothers.
Allergy to investigational drugs or to red chili peppers.
Chronically use of analgesics (not limited to, but including: non-steroidal
anti-inflammatory medications, steroids, anti-depressants, anti-convulsants).
Presence of chronic disease (e.g. cardiovascular disease, liver disease, kidney disease,