Gabapentin: The First Preemptive Anti-Hyperalgesic for Opioid Withdrawal Hyperalgesia?

Abstract

Departments of Anesthesiology and Pharmacology & Toxicology, Queen's University, Kingston, Ontario, Canada. gilroni@post.queensu.caIn Reply:—The above letter responds to the provocative question of whether gabapentin is a “broad spectrum” analgesic 1and appropriately points out that things are not quite so simple.Gustorff et al. postulate that the effects of gabapentin reported by Dirks et al. 2are not due to antinociception but, rather, to the suppression of hyperalgesia caused by withdrawal from intraoperative opioids. This is a reasonable hypothesis; however, it should be noted that Fassoulaki et al. recently observed similar reductions in pain and opioid consumption with gabapentin in patients who received no intraoperative opioids. 3Therefore, gabapentin's effects cannot be solely due to suppression of opioid withdrawal hyperalgesia.Nevertheless, this raises questions central to understanding the modulation of pain by gabapentin. While Gustorff et al. correctly indicate that postoperative pain is predominantly nociceptive, they fail to emphasize the importance of spinal sensitization, 4which contributes to hyperalgesia and allodynia and which may be suppressed by gabapentin. Indeed, although gabapentin has little antinociceptive effect in the uninjured organism, it has been shown, in the absence of opioids, to reduce pain responses after surgical tissue injury. 5The latter comments by Gustorrf et al. illustrate the complexities of interpreting gabapentin's effect when administered with opioids. Ethical conduct of most postoperative trials requires the provision of rescue analgesia, often in the form of patient-controlled analgesia with morphine, which necessitates the integration of pain measures with morphine consumption as co-relevant outcome measures. 6Although trials have been equivocal thus far, 7,8the possibility that mechanisms of opioid tolerance 9contribute to postoperative hyperalgesia and increased opioid requirements may confound results of analgesic trials. Therefore, gabapentin trials involving concomitant morphine administration must be interpreted in light of a possible interaction between these drugs. In this regard, we have observed in the rat that gabapentin prevents the development of morphine tolerance and partially reverses established tolerance indicating that such an interaction indeed exists. 10Thus, although follow-up studies will further characterize the role of gabapentin in postoperative pain, even more sophisticated strategies are needed to distinguish between its specific pharmacological effects (e.g. , analgesia, antihyperalgesia, antiallodynia and reversal of opioid tolerance).