Pain is the most common reason why patients seek health care and usually is the consequence of tissue damage that occurs during or after medical illness, surgery, or trauma including chemical and thermal injuries. More recently, pain has been regarded as a fifth vital sign along with blood pressure, heart rate, temperature, and respirations. Fortunately, the understanding of the neurophysiologic mechanisms by which noxious and non-noxious stimuli are perceived has substantially improved over the last few years and new drugs and techniques have been developed to treat pain. However, the mechanisms of pain are not entirely understood and humans still have a great deal of pain while in the hospital and many have debilitating chronic pain throughout their lives. The purpose of this study is to establish a non-injurious neuro-specific nociceptive assay in mice. To this end, we are using an FDA-approved neuro-stimulator that is currently used in humans for the diagnosis of pain syndromes and neurologic diseases. This device delivers electrical stimuli to the skin at different frequencies and intensities, and produces transient discomfort without producing injury. Given that currently used pain models have limitations and may produce some tissue-injury in order to induce pain, the development of a non-injury producing animal model would add an invaluable tool for the study of the mechanisms of pain. With this study, we have used a technique that does not stimulate the peripheral cutaneous nerve organ used for the transmission of a painful stimulus (nociceptors), does not produce tissue-injury, and yet produces transient discomfort and pain-avoiding behavior by stimulating specific nerve fibers. Under DASS 02-01 we completed pilot studies for the development of a non-injurious neuro-specific nociceptive assay in mice, developed normative values for the response to each frequency, and have fully developed a software application to control the neuro-stimulator and automate a large portion of the protocol. The automation also required the development of custom hardware, which is also used to digitally record sensor signals and events. Subsequent investigations will further validate the model and demonstrate its value for studies of the mechanisms of pain and pharmacodynamics of new therapeutic agents to treat pain.
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