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

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.

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.