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

• Effects of inflammation in periradicular tissues. [ Time Frame: Immediately following tooth extraction and dental pulp procurement. ] [ Designated as safety issue: No ]
  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.
  
  

• Altered pain reports. [ Time Frame: 24 hour post-tooth extraction. ] [ Designated as safety issue: No ]
  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.
  
  

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.