Bradykinin Receptors and Pain

NCT00083356 | Completed Phase 2

• 2 other identifiers: 04018204-NR-0182
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

This study will examine whether bradykinin receptors are produced at the site of wisdom tooth extraction and if they contribute to the amount of inflammation and pain that follows surgery. Bradykinin is a molecule produced by enzymes at the site of an injury and then binds to receptors to cause pain. The study will also evaluate the role of genetic factors in the production of bradykinin and their receptors and the pain associated with minor surgical procedures. Patients between 16 and 35 years of age who are referred to the NIH dental clinic for removal of two wisdom teeth may be eligible for this study. Candidates must be in good health and must not be allergic to aspirin, non-steroidal anti-inflammatory drugs, sulfites, or amide anesthetics. They will be screened with a medical history and oral examination, including x-rays to confirm the need for wisdom tooth extraction. On the morning of surgery following an overnight fast, participants have a blood sample drawn to extract DNA for gene studies. Just before surgery, they are given an intravenous (IV) sedative to induce drowsiness and a local anesthetic to numb the mouth. They are also given IV either Ketorolac, a non-steroidal anti-inflammatory drug, or placebo, a look-alike medication with no active ingredient. After the extractions, a small piece of plastic tubing is placed in both extraction sites, and every 20 minutes for the next 3 hours inflammatory fluid is collected from the tubing for measuring chemicals believed to cause pain and swelling. Patients rate their pain by answering pain-related questions every 20 minutes. Patients who have pain that is not relieved by the study medication (Ketorolac or placebo) are given, upon request, 50 mg of the pain reliever tramadol (Ultram). Patients remain in the clinic for at least 3 hours and no more than 7 hours after surgery in order for monitoring the effects of the study drugs as the local anesthetic wears off. Patients undergo two biopsies during the study - one before and one after the extraction - to measure any changes in chemicals produced in response to the surgery. The second biopsy is done either 3, 7, or 24 hours after the extraction. Patients in the 3- and 7-hour groups are given a small dose of local anesthetic in the gum for the second biopsy and remain in the clinic until the biopsy is done; those in the 24-hour group are given forms to record pain ratings at home and return to the clinic the following morning for a 2-hour follow-up visit. All patients are given standard pain medication (flurbiprofen) to take at home.

Conditions

Tooth, Impacted

Keywords

Pain; Kinins; Inflammation; Gene Expression; Oral Surgey; Bradykinin B1 Receptors; Acute Peripheral Inflammation; Inflammatory Gene Expression; Wisdom Teeth; Third Molar Extraction

Interventions

Wisdom tooth extraction PROCEDURE

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female volunteers referred for third molar extraction willing to undergo 2 or 3 visits: 1 screening visit; 1 surgical appointment; and a possible follow-up research-related appointment
• Between the ages of 16 to 35 years (based upon eruption patterns and age-related complications associated with surgical extraction of third molars
• In general good health- American Society of Anesthesiologists (ASA) status I or II (healthy subjects based upon criteria for safe administration of out-patient conscious sedation)
• Willing to undergo observation period for three hours postoperatively
• Ability to complete a 100 mm visual analog scale and a category scale every 20 minutes for the first 3 postoperative hours
• Willing to have a microdialysis probe placed beneath the surgical flap during the first 3 hours post-surgery
• Willing to have a preoperative biopsy on the day of surgery, and a postoperative biopsy either at 3, 7 or 24 hours following surgery
• Willing to return, if needed, 24 hours post-operation for the postoperative biopsy
• Must have two lower partial (rating is equal to 3) or fully impacted (rating is equal to 4) wisdom teeth (mandibular third molars)
• As assessed at the screening visit, the sum of the mandibular third molar surgical difficulty ratings must be between 6 to 8 in order to evaluate subjects experiencing similar pain levels

You may not qualify if:

• Patients who are allergic to aspirin, NSAIDs, sulfites, or amide anesthetics
• Patients who have had asthma, or hives
• Patients who are pregnant or nursing
• Patients with history of peptic ulcers and/or GI bleeding
• Chronic use of medications confounding the assessment of the inflammatory response or analgesia, for example, NSAIDs, COX-2 inhibitors, antihistamines, steroids, antidepressants
• Patients who have clinical signs suggestive of infection, inflammation, or pre-existing pain at either extraction site
• Patients with severe kidney disease
• Patients who are taking any of the following drugs: ACE inhibitor; potassium sparing diuretics; aspirin on a near daily basis; coumadin or other blood thinners
• Patients who are taking drugs known to inhibit P450 2C9 and drugs metabolized by P450 2D6
• Unusual surgical difficulty (determined from panoramic radiograph or during the actual surgery)

Sponsors & Collaborators

• National Institute of Nursing Research (NINR): lead

Study Sites (1)

National Institute of Nursing Research (NINR)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Walker K, Perkins M, Dray A. Kinins and kinin receptors in the nervous system. Neurochem Int. 1995 Jan;26(1):1-16; discussion 17-26. doi: 10.1016/0197-0186(94)00114-a.

  PMID: 7787759 BACKGROUND

• Ahluwalia A, Perretti M. B1 receptors as a new inflammatory target. Could this B the 1? Trends Pharmacol Sci. 1999 Mar;20(3):100-4. doi: 10.1016/s0165-6147(99)01321-8.

  PMID: 10203864 BACKGROUND

• Bock MG, Longmore J. Bradykinin antagonists: new opportunities. Curr Opin Chem Biol. 2000 Aug;4(4):401-6. doi: 10.1016/s1367-5931(00)00107-1.

  PMID: 10959767 BACKGROUND

MeSH Terms

Conditions

Tooth, Impacted; Pain; Inflammation

Condition Hierarchy (Ancestors)

Tooth Diseases; Stomatognathic Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: May 21, 2004
• First Posted: May 21, 2004
• Study Start: May 1, 2004
• Study Completion: February 1, 2006
• Last Updated: March 4, 2008

Record last verified: 2006-02

Locations

US (1)