To the Editor:—

The recent study of Carli et al.  1provides valuable evidence that enhanced postoperative analgesia with an epidural catheter can improve outcome in terms of quality of life. A mock epidural catheter in the control group might have added further assurance that nonblinding did not lead to differential treatment or expectations between the study groups, but the authors did an excellent job of standardizing postoperative care to minimize this effect.

However, recent advances in the study of pain treatments suggest that an additional control should be present in studies on the efficacy of epidural compared to intravenous analgesia. The group receiving intravenous analgesia should also receive low dose intravenous or subcutaneous local anesthetic, to produce plasma levels comparable to those in the epidural group. Local anesthetic at plasma levels achieved with nontoxic intravenous administration or prolonged epidural administration has been shown to have analgesic properties in animal models both in vitro  2,3and in vivo , 2and in humans. 4,5Of particular relevance to the issue of whether “diminishing postoperative pain may decrease the incidence of long-term chronic pain”6is the efficacy of intravenous local anesthetic in treating neuropathic pain models. 2,5The mechanism(s) of this effect remains to be elucidated, but occurs at levels too low to block sodium channels, and may involve effects on neuronal calcium homeostasis 3,7and frequency of sodium channel response to stimuli. 2Low-dose local anesthetics also have significant antiinflammatory effects, 8and the levels of acute phase inflammatory proteins may affect subjective acute postoperative physical well being. 9 

This comment is not specific to Carli et al.  1Unfortunately, most if not all clinical studies of epidural anesthesia on outcome have neglected this control, even those that have rigorously included an epidural catheter in subjects not receiving epidural analgesia to blind the study;e.g. , Norris et al.  10 

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Strichartz GR, Zhou Z, Sinnott C, Khodorova A: Therapeutic concentrations of local anaesthetics unveil the potential role of sodium channels in neuropathic pain. Novartis Found Symp 2002; 241: 189–201
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