Understanding pain modulatory systems in the brainstem and spinal cord requires a detailed understanding of the anatomic connections among the neurons in these regions of the nervous system because the circuit diagram forms the basis for understanding the function of this extended neuronal network. However, this is a highly challenging endeavor because the specific connections among these neurons, and the functions they subserve, appear to be different in different animal species and even among different stocks and strains of the same species. Such anatomic differences can confuse the interpretation of studies that determine the function of these neuronal systems by using different rat stocks and strains. These conclusions emphasize the continued importance of anatomic investigations to advances in our understanding of pain mechanisms and argue for the use of strains and stocks of rats for which the anatomic circuitry is well-defined. Last, in view of the increased emphasis that has been placed on the use of gene-targeting strategies in different inbred strains of mice to understand the mechanisms of pain modulation, it will become increasingly important to have a detailed understanding of the potential differences in the neural circuitry of the pain modulatory pathways in this species as well.
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