In Vitro Studies on Pharmacological Regulation and Genetic Risk Factors of Peripheral Human Nociceptors

Study Overview
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Brief Summary
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This protocol is for a number of in vitro studies using human surgical biopsies and evaluating the pharmacology and genetics of human nociceptors (pain detecting) neurons

Detailed Description
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Purpose/Objectives a. Specific Aims Specific Aim 1: Characterize in humans the effects of inflammation and neuronal degeneration on peripheral levels of NPY, and related Y receptors (Y1, Y2, Y5) in periradicular tissue. Specific Aim 2: Determine whether NPY inhibits neurosecretion from peripheral terminals of capsaicin-sensitive neurons innervating normal versus inflamed tissue. Specific Aim 3: Determine whether peripheral administration of NPY is analgesic and/or anti-allodynic in patients experiencing spontaneous pain and mechanical allodynia in a clinical model of inflammation with associated neuronal degeneration. Specific Aim 4: Evaluate whether population characteristics are associated with altered pain reports. First, we will determine whether patients with the C1128 single nucleotide polymorphism (SNP) of the PreProNPY gene, whose phenotype confers substantially augmented peripheral NPY neurosecretion, report less pain compared with patients without this genetic polymorphism. Second, we will determine whether ethnic/cultural factors associated with an underserved minority population (Hispanics in the San Antonio area) are associated with altered pain reports.

Official Title
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Studies on Normal and Inflamed Dental Pulp, NPY Regulation of Peripheral Human Nociceptors, Peripheral Mechanisms of Opioid Analgesia, Cannabinoid-induced Desensitization of TRPV1 Receptors Adrenergic Modulation of Trigeminal Nociceptors

Conditions
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Pain

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willingness to participate; identified indication to have a tooth extraction; 16-90 years old; diagnosis of normal pulp; or diagnosis of irreversible pulpitis requiring a symptom of spontaneous pain and positive and lingering response to pulp vitality test. Exclusion Criteria: History of taking steroids within the last month; history of taking analgesics in the last four hours.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of inflammation in periradicular tissues. | Extracted human teeth are sectioned to obtain the crown dental pulp which is placed in a well plate. The pulp is moved every twenty minutes through proprietary substances for a total of 60 to 120 minutes depending on the specific experiment. After each 20 minute fraction, the buffer solution in each well plate is collected, labeled and placed in the -80 freezer along with the pulp sample. | Immediately following tooth extraction and dental pulp procurement. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Altered pain reports. | Patients provide perceived pain within the first 24 hours post-extraction via a take-home pain postcard. The postcard has a Visual Analog Scale pain graft that the patient marks and returns via mail. | 24 hour post-tooth extraction. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain in teeth