Liu S, et al. - The role of sonic hedgehog (Shh) signaling in opioid-induced hyperalgesia and tolerance was investigated. Researchers noted hyperalgesia and tolerance to be obvious with repeated administration of morphine. A Significant delay in the generation of morphine-induced hyperalgesia (MIH) and tolerance was noted with pharmacologic and genetic inhibition of Shh signaling in addition to the associated neurochemical changes. Findings thereby suggest that Shh signaling may be a critical mediator for MIH and tolerance by regulating brain-derived neurotrophic factor expression. Inhibition of Shh signaling, particularly during the early phase, could be effective in delaying or suppressing MIH and tolerance.