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This multimodal non-opioid pain management regimen, studied by the Henry Ford Health System, consists of a combination of four medications: ibuprofen, pregabalin, acetaminophen, and tizanidine. Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenase enzymes to reduce inflammation and pain. Pregabalin is a gabapentinoid that binds to the alpha-2-delta subunit of voltage-gated calcium channels, modulating the release of excitatory neurotransmitters to treat neuropathic and acute pain. Acetaminophen provides analgesic and antipyretic effects through central mechanisms, while tizanidine acts as a centrally acting alpha-2 adrenergic agonist to reduce muscle spasticity and provide supplemental analgesia. This regimen is being evaluated in Phase 4 clinical trials as an alternative to standard opioid-based analgesia for patients undergoing orthopedic procedures, such as open reduction and internal fixation (ORIF) of clavicle fractures, to mitigate the risks associated with opioid use.
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