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Further examining the change in gene expression revealed that an extensive number of these metabolic genes are increased in expression both at 24 h and 48 h (Extended Data Fig

454 This might be caused by factors such as the method of administration, the expectations of patients or researchers, and gender differences in pain reports

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the inventors also surprisingly found inhibitory activity with certain embodiments of the invention where R 1 is methyl with dual positional substitutions (see e.g., compounds 2j, 2m, 2k, and 2l, Table 2)

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