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At concentrations of 1 pM1 nM, DSIP stimulated calcium-dependent release of immunoreactive Met-enkephalin from rat lower brainstem slices in vitro suggesting any antinociceptive effects observed in animal models may be mediated through endogenous opioid peptide release rather than direct receptor binding [7]

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Additionally, Dihexas small molecular weight of 750 Da allows blood-brain barrier penetration approximately 1000-fold more efficient than BDNF, which is too large to cross the BBB effectively when administered peripherally