Although pain is still the most common reason why patients seek health care, the mechanisms of transmission and perception of pain are not entirely understood. Understanding of the neurophysiologic mechanisms by which noxious and non-noxious stimuli are perceived is imperative for the development of new drugs and techniques to treat pain. Therefore, animal models of pain are necessary to further our understanding of the mechanisms of pain transmission. Currently available models to study transmission of pain use heat, pressure, or chemical stimulation to inflict pain. These models have led to many discoveries in the field but have limitations. Some of the limitations include the fact that heat and pressure can be associated with injury to animals, the stimuli can nonspecifically stimulate several types of nerve fibers (A beta-pressure, A delta-sharp pain, C-slow burning pain), and these stimuli can be associated with habituation learning. In order to study the mechanisms of the transmission of noxious stimuli, we developed a novel and non-injurious nociception assay to preferentially study transmission of noxious stimulus via nerve fibers in a live system. We use a neuro-stimulator that delivers electrical stimuli to the skin at different frequencies and intensities and produces transient discomfort without producing injury. Each of the electrical frequencies used preferentially stimulate a specific type of pain fiber and allows for the measure of vocalization threshold for each type of pain fiber. In the model, we define vocalization as the pain avoiding behavior to the electrical stimulus and use it as the end point to measure current vocalization threshold for each of the pain fibers. Unlike currently used pain models that may produce some tissue-injury in order to induce pain, this assay is non-injurious and preferentially stimulates each type of pain fibers. Therefore it might become a valuable tool for the study of the mechanisms of pain. ? We completed pilot studies for the development of this assay in mice, developed normative values for the response to each frequency, and have fully developed software application to control the neuro-stimulator, and automated a large portion of the protocol. In addition, we are implementing upgrades to enable completely automated data collection and storage. We are now using the model to study the impact of aging as well as the role of neuronal nitric oxide in the transmission of noxious stimuli in specific nociceptive nerve fibers. We are further developing the model to evaluate pharmacologic interventions with systemic and local analgesics, different strains and species of animals, and different pain models.

Agency
National Institute of Health (NIH)
Institute
Clinical Center (CLC)
Type
Intramural Research (Z01)
Project #
1Z01CL008056-04
Application #
7332171
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2006
Total Cost
Indirect Cost
Name
Clinical Center
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Finkel, Julia C; Quezado, Zenaide M N (2007) Hypothermia-induced bradycardia in a neonate receiving dexmedetomidine. J Clin Anesth 19:290-2
Finkel, Julia C; Pestieau, Sophie R; Quezado, Zenaide M N (2007) Ketamine as an adjuvant for treatment of cancer pain in children and adolescents. J Pain 8:515-21
Finkel, Julia C; Besch, Virginia G; Hergen, Adrienne et al. (2006) Effects of aging on current vocalization threshold in mice measured by a novel nociception assay. Anesthesiology 105:360-9