Can inflammatory pain prevent the development of acute tolerance to alfentanil?
Constant pain could, in principle, counteract mobilization of antianalgesia systems and prevent the development of acute tolerance to the analgesic effects of opioids. We sought to determine whether a tonic nociceptive input caused by inflammation inhibits the development of acute tolerance to alfentanil. The inflammation was induced by injection of carrageenan into the rat hind paw. A threshold of motor response to increasing pressure on the paw was used to determine analgesia. Alfentanil was administered IV with an infusion algorithm designed to maintain a constant plasma level of opioid for 4 h. The degree of acute tolerance was determined on the basis of decline in the level of analgesia. The continuous decline of the analgesic effect from its peak at 30 min to the end of the 4-h infusion period was profound, despite the constant-rate infusion of alfentanil. The degrees of decline were very similar in rats with and without carrageenan-induced inflammation (from 242 +/- 31 to 154 +/- 20 g, P < 0.0001; and from 242 +/- 33 to 148 +/- 14 g, P < 0.0001, respectively). The results suggest that inflammatory nociceptive input does not prevent the development of acute tolerance to opioid-induced analgesia measured as an increased reaction threshold to painful pressure. We conclude that acute tolerance to the analgesic effect of opioids is profound and develops very rapidly, even in the presence of constant nociceptive input.


CONCLUSIONS
We examined whether inflammatory pain can prevent the rapid decline in analgesic effectiveness (acute tolerance) of alfentanil during its IV infusion. We found that acute tolerance to the analgesic effect of alfentanil, in the presence of constant pain caused by inflammation, develops as rapidly as without it.
Kissin
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Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, USA. kissin@zeus.bwh.harvard.edu
Bright
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CA
Bradley
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EL
D015760:Alfentanil / Q000627:therapeutic use*; D000698:Analgesia; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000818:Animals; D002351:Carrageenan; D004361:Drug Tolerance / Q000502:physiology*; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D017288:Pain Threshold; D051381:Rats; D017207:Rats, Sprague-Dawley
D000701:Analgesics, Opioid; D015760:Alfentanil; D002351:Carrageenan