To the Editor:—

It was with great interest that we read the study of Dirks et al. , who found a substantial reduction in postoperative morphine consumption over 4 h after remifentanil-based anesthesia for radical mastectomy by preoperative application of a single dose of 1200 mg oral gabapentin. 1The authors suggested either a potential effect of gabapentin on acute pain or the potential modulation of intraoperative induction of opioid tolerance. In an accompanying editorial, Gilron pointed out the vast analgesic potency of gabapentin in humans. 2 

However, in a human inflammatory pain model, 1200 mg gabapentin reduced neither the primary hyperalgesia to heat nor the secondary hyperalgesia to pinprick. 3In the human heat-capsaicin model, 1200 mg gabapentin reduced the secondary hyperalgesia to pinprick but did not affect the primary hyperalgesia response. 4Hence, in accordance with studies in chronic pain, 5,6gabapentin provides antihyperalgesic but not antinociceptive properties. Postoperative pain, however, is predominantly nociceptive in origin.

Dirks et al.  performed high-dose remifentanil-based anesthesia using 0.4 μg/kg/min. It is well known that opioids may induce hyperalgesia. 7In particular the transition from short-acting opioids may be accompanied by hyperalgesia. 8Because remifentanil does not induce acute opioid tolerance, 9an increase in postoperative morphine consumption after high-dose remifentanil-based anesthesia may be explained by the development of opioid withdrawal hyperalgesia. 10 

Dirks et al.  studied only the immediate postoperative stage for a period of 4 h. Any information about the postoperative morphine consumption over the first 24 h is lacking. Taken together they may, therefore, have studied remifentanil withdrawal induced hyperalgesia after mastectomy. Thus we suggest that gabapentin may not be a “broad-spectrum” analgesic for postoperative pain therapy, but rather the first effective antihyperalgesic drug for the preemptive treatment of transient hyperalgesia after short-acting opioid-based anesthesia. Further studies are needed to test this fascinating aspect of gabapentin.


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Gilron I: Is gabapentin a “Broad-spectrum” analgesic? A nesthesiology 2002; 97: 537–9
Werner MU, Perkins FM, Holte K, Pedersen JL, Kehlet H: Effects of gabapentin in acute inflammatory pain in humans. Reg Anesth Pain Med 2001; 26: 322–8
Dirks J, Petersen KL, Rowbotham MC, Dahl JB: Gabapentin suppresses cutaneous hyperalgesia following heat-capsaicin sensitization. A nesthesiology 2002; 97: 102–7
Backonja M, Beydoun A, Edwards KR, Schwartz SL, Fonseca V, Hes M, LaMoreaux L, Garofalo E: Gabapentin for the symptomatic treatment of painful neuropathy in patients with diabetes mellitus: A randomized controlled trial. JAMA 1998; 280: 1831–6
Gustorff B, Nahlik G, Spacek A, Kress HG: Gabapentin in the treatment of chronic intractable pain. Schmerz 2002; 16: 9–14
Eisenach JC: Preemptive hyperalgesia, not analgesia? A nesthesiology 2000; 92: 308–9
Koppert W, Dern SK, Sittl R, Albrecht S, Schuttler J, Schmelz M: A new model of electrically evoked pain and hyperalgesia in human skin: The effects of intravenous alfentanil, S(+)-ketamine, and lidocaine. A nesthesiology 2001; 95: 395–402
Gustorff B, Nahlik G, Hoerauf KH, Kress HG: The absence of acute tolerance during remifentanil infusion in volunteers. Anesth Analg 2002; 94: 1223–8
Guignard B, Bossard AE, Coste C, Sessler DI, Lebrault C, Alfonsi P, Fletcher D, Chauvin M: Acute opioid tolerance: Intraoperative remifentanil increases postoperative pain and morphine requirement. A nesthesiology 2000; 93: 409–17