Over the last several years, the scientific literature has been replete with numerous new approaches to the treatment of pain. Unfortunately, approaches that were promising in the laboratory do not always translate to better clinical treatments. Similarly, the underlying physiology and clinical relevance of some animal pain models used to evaluate these new treatments have not been clearly demonstrated. One of the reasons for these disparities may have to do with the fact that some analgesic treatments appear to differentially attenuate only some kinds of nociception. Some standard tests then, may miss the potential utility of a treatment for a pain type that is not modeled by those tests. One distinction that we have found to be important in determining antinociceptive capacity of treatments is whether, and to what extent a nociceptive response is mediated by the activation of unmyelinated or myelinated primary afferent nociceptors. Another reason that results of rodent tests do not always predict clinical outcomes and vice versa may be the phylogenetic distance between humans and rodents. It is likely that testing potential treatments using non-human primates models might be more predictive of clincial utility in some cases. Thus, there is a need for the development of a primate assay which allows for the differential assessement of nociception mediated by myelinated or unmyelinated nociceptors. The purpose of the work outlined in this proposal is to provide preliminary evidence that the principles determined in rodents with regards to differential testing of Adelta and C fiber mediated nociception are also applicable to the testing of non-human primates. The experiments described here make use of demonstrated differences in the sensitivity of nociception mediated by myelinated or unmyelinated nociceptors to different rates of skin heating, topical application of the neurotoxin capsaicin, and the systemic application of the opiate analgesic morphine. The goal of this work is to develop a primate nociceptive assay which will allow for better predictions of the clinical utility of novel approaches to the treatment of pain.
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