SBIR-STTR Award

The goal of this Phase I SBIR is to design, develop, build and test a new prototype of infra red laser thermal stimulator that can be used for differential activation of C and A-delta fibers (nociceptors) in humans. C and A-delta fiber nociceptors transduce and mediate pain of different sources, and are therefore responsible for carrying different types of pain information to the central nervous system. Clinical pain of different underlying pathologies can be differentially mediated by the activation of these two pain fiber types. Thus, the capacity of differential activation of C or A-delta fiber nociceptors in patients may allow for more specific diagnosis, better predictive power in pharmaceutical prescription, and better capacities to follow the clinical progress of the underlying disease. Currently, no tool is available to do the reproducible selective activation of C and A delta fibers in humans and clinically used thermal stimulators rely on electronically controlled contact heaters (Peltier thermodes). These, however, require conductive heating of pain fibers through overlying layers of skin. Similarly, laser stimulators commonly in use for research purposes (CO2 and Thullium) deposit energy entirely on the skin surface, whereas the nociceptors are located deeper in the skin. Thus, for both Peltier thermodes and these lasers, direct heating/activating of nociceptors is impossible, but requires potentially dangerous, high surface temperatures. The laser stimulation system that we propose to develop will use infrared coherent light that, due to its wavelength, allows for direct stimulation of underlying tissue that contains the nociceptor endings. Furthermore, our preliminary evidence suggests that, by altering the parameters of the laser stimulus, we can selectively activate either C or A-delta fibers, potentially allowing for a highly useful clinical tool. Thus, this proposal describes development and experimental work, which should allow for the development of a prototype stimulator that allows for selective activation of C or A-delta fibers in humans

Thesaurus Terms:
afferent nerve, biomedical equipment development, computer system design /evaluation, heat stimulus, laser, nociceptor, pain, personal computer bioengineering /biomedical engineering, clinical research, human subject, patient oriented research

The goal of this Phase II SBIR project is to develop and validate an efficient and consistent selective stimulator to assess A-delta and C fiber pain sensing neurons (nociceptors) for use with human volunteers for new drug evaluation and with pain patients to aide in diagnosis. There is currently no commercially available tool of similar capabilities on the market. Evaluation of thermal pain sensitivity in humans can be useful in describing the potential utility of putative analgesic drugs. The ability to reliably, differentiate pain mediated by the activation of unmyelinated (C) or myelinated (A-delta) nociceptors may also provide allow for more accurate prediction of the efficacy of pain treatments. There is also a potential utility of being able to differentially as certain pain mediated by these two afferent types in establishing a diagnosis for, and following the progress of patients in pain. Thus, it is our overall goal to establish stimulation protocols for use with our unique infrared diode laser that will allow, in humans, for the differential assessment of pain evoked by the activation of these two nociceptor types, and to test these protocols using benchmark pharmacologic agent. Thus, we hypothesize that the infrared diode laser will prove safe and reliable, such that it, and its components will be certifiable for meeting FDA requirements for non-invasive skin heating. To do this, we will determine the stimulus intensity margin between pain threshold measurement and skin damage. In addition, we will insure complete compatibility of the laser with functional magneto-resonance imaging systems and EEG cortical evoked potential recording systems, making any hardware and software adjustments that are necessary. We will also submit the laser and its components for certification as to electrical and magnetic interference and for medical laser safety standards, and make any device changes that are necessary to meet the requirements. We will also insure that the device protocols will allow for accurate and differential assessment of proalgesic and analgesic effects of drugs known to differentially affect C or A-delta nociceptors, including the TRPV1 agonist capsaicin, the A-delta sensitizing solvent dimethyl sulfoxide (DMSO), and the mu opioid analgesic morphine. To do this, we will assess psychophysical and cortical (EEG) responses evoked by brief pulses that activate A-delta nociceptors, or longer pulses that activate C fiber nociceptors.

Thesaurus Terms:
There Are No Thesaurus Terms On File For This Project.