Perioperative nimodipine and postoperative analgesia

Opioids are the mainstay of treating acute postoperative pain. However, they are associated with a number of adverse events, including nausea and vomiting, respiratory depression, mood alteration, and pruritus. Treatment with adjunctive analgesic drugs can have a morphine-sparing effect, thereby reducing these side effects. This has been demonstrated with nonsteroidal antiinflammatory drugs, such as diclofenac (1), but these drugs are associated with their own adverse event profile, including gastrointestinal hemorrhage and renal impairment. There is growing evidence suggesting that voltage-gated calcium channels have an important role in the transmission of nociceptive impulses. Subtypes of voltage-gated calcium channels include L-, N-, and T- Ca2+ calcium channels. Calcium influx and efflux from sensory neurons appears to facilitate nociceptive neurotransmitter release in the spinal cord (2). Acute opioid exposure decreases intracellular calcium levels and Ca2+ binding to synaptic membranes (3). Conversely, increases in intracellular Ca2+ are associated with development of central sensitization after a noxious insult (4). L-type voltage-gated Ca2+ channels have been shown to have a functional role in morphine antinociception in a diabetic rat model (5). It seems logical to hypothesize, therefore, that inhibition of Ca2+ into sensory neurons using calcium antagonists might reduce pain and requirement for morphine in clinical situations. Nimodipine is a dihydropiridine calcium channel antagonist, which binds to the L-type voltage gated calcium channel. It crosses the blood-brain barrier and is demonstrably effective in the prevention of secondary ischemic neurological damage after subarachnoid hemorrhage (6). There are case reports of its efficacy when administered epidurally in reducing pain and opioid requirement in patients receiving palliative analgesic therapy (7). However, a placebo-controlled cross-over study in cancer patients failed to demonstrate any analgesic benefit of oral nimodipine (8). We tested the hypothesis in a randomized, double-blind, placebo-controlled clinical trial that perioperative nimodipine commenced preoperatively and continued for 48 h postoperatively would reduce pain and morphine requirements.N/