It is clear that there are many adjuvants and nonopioid analgesics available to physicians for the treatment of pain and that polypharmacy in pain management is more likely to be the rule rather than the exception. Combining multiple agents that inhibit the pain transmission system at different levels is more likely to have success than any single agent alone and may allow for lower doses of each agent so as to reduce potential adverse or side effects. Combining agents that have NMDA receptor blocking action, Mu opioid agonist action, tetrodotoxin resistance (TTXr) sodium channel blockers, SNRI, neuronal calcium channel blockade, and anti-inflammatory actions can all contribute to central nervous system protection. Combining oral gabapentin (Neurontin®) 300-1,200 mg (Dirks et al. 2002, Gilron 2002, Matthews and Dickerson 2002, Hayashida et al. 2008, Begon et al. 2002) or pregabalin 75-150 mg (Lyrica®), and clonidine 0.2 mg along with acetaminophen 1,000 mg, and a COX-2 inhibitor (celecoxib 200 mg) (Celebrex®®) preoperatively, and then continuing postoperatively with the antineuropathic regimen of gabapentin or pregabalin (100-300 mg tid or 50 mg tid, respectively) (Begon et al. 2002) along with an appropriate opioid, anti-inflammatory, and antidepressant (for SNRI action) until wound healing has occurred could potentially reduce or eliminate the development of chronic pain after surgery. On this basis we can begin to target polypharmacy to help the brain to modulate neuropathic pain (Weissman and Haddox 1989). This is similar to the multimodal therapeutic recommendations of Power (2005).

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