Double Blinded, Randomized, Placebo Controlled Study in Evaluating the Role of Pregabalin in Reducing Opioid Requirement in Spinal Fusion Surgeries of Two or More Vertebrae

Introduction

Postoperative pain is often thought to be inadequately treated in half of all surgical procedures . Postoperative pain management in patients undergoing spine surgery is often difficult and challenging. The challenges of opioid tolerance and paucity of efficient opioid sparing agents makes pain management even more complex. Preoperative strategies that can minimize postoperative pain include proper surgical technique, which would avoid or lessen nerve injury, and the use of preemptive analgesia. Studies have shown that the intensity of acute postoperative pain correlates with the risk of developing persistent pain. Post operative pain results from the direct activation of nociceptors, inflammation, and in some cases direct nerve injury to the nerves.

The data on preemptive analgesia are inconclusive . The concept, however, has sparked interest in mechanism-based analgesia and highlighted the process of central sensitization as a target for analgesic intervention .

The use of opioids is limited by their side effect profile and by the poor response of certain types of pain . The multiplicity of mechanisms involved in pain suggests that combination of opioid and non-opioid analgesic drugs will enhance analgesia. The concomitant reduction in opioid requirements, anticipated with the use of multimodal therapy, can also be expected to reduce side effects.

Pregabalin is a lipophilic gamma-amino-butyric acid (GABA) analog with anticonvulsant, anxiolytic and sleep-modulating properties. The effectiveness of pregabalin has been demonstrated in several pain models including neuropathic pain , , incisional injury and inflammation . Several previous studies conducted found that the use of gabapentin, the predecessor of pregabalin, reduced post operative pain and opioid requirements and decreased the number of opioid related adverse events , . Pregabalin is the pharmacologically active S enantiomer of 3-aminomethyl-5-methyl hexanoic acid; it has a similar pharmacological profile to gabapentin . Like gabapentin, pregabalin also binds to the α-2-δ subunit of voltage gated calcium channels, reducing the release of excitatory neurotransmitters: glutamate, norepinephrine, serotonin, dopamine and substance-P. It blocks the development of hyperalgesia and inhibits central sensitization , . Pregabalin has greater absorption, bioavailability, anticonvulsant, anti-hyperalgesic and anxiolytic properties than gabapentin , .