Correspondence  |   August 2001
When Is Preemptive Analgesia Truly Preemptive?
Author Affiliations & Notes
  • Argyro Fassoulaki, M.D., Ph.D., D.E.A.A.
  • *University of Athens, Athens, Greece.
Article Information
Correspondence   |   August 2001
When Is Preemptive Analgesia Truly Preemptive?
Anesthesiology 8 2001, Vol.95, 565-566. doi:
Anesthesiology 8 2001, Vol.95, 565-566. doi:
To the Editor:—
We read with interest the article of Aida et al.  , 1 and we wish to point out our concerns. First, the authors use the term preemptive analgesia even though they treated the three groups with analgesics both before and after the surgical incision. Such a study design is not appropriate to demonstrate a preemptive effect because no comparison is attempted between similar analgesic interventions applied before or after the start of the surgical stimulus. 2 Furthermore, before the start of the stimulus, nitrous oxide, which has a preemptive effect, was administered to all groups. 3 
Second, the authors report that “for definitive preemptive analgesia, blockade of opioid and N  -methyl-d-aspartate [NMDA] receptors is necessary,” and that “This mechanism (dual blockade of opioid and NMDA receptors) may account for the current results.”1 Apparently, there is a misconception because it is the activation of the opioid receptors by an agonist (and not their “blockade”) that exerts an antinociceptive effect.
Third, why did the authors need a control group when their assumption could have been tested by an enhanced analgesic effect in the combination group? For the same reason, the use of naloxone is not justifiable. On the contrary, it is hard to persuade for the precise dose of naloxone required to reverse the aftereffect of epidural morphine and at the same time to allow the postoperative morphine to produce analgesia. The authors report that the naloxone administered neither increased postsurgical pain nor interfered with the postoperative morphine, but this is based on a retrospective observation. At the time of the design and conduct of the study, it would not be possible to predict the response of the patients.
Fourth, whether the vagus nerve conveys visceral true nociceptive information and to what degree remain controversial. 4 Vagal afferent pathways may have a modulatory antinociceptive and analgesic effect, and dorsal horns and spinothalamic tracts receive vagal inhibitory influences. 5 It seems more likely that the primary nociceptive input from the stomach comes from the afferent fibers following the sympathetic route to the dorsal horns. 4 With regard to the effects of the gastrectomy in particular, it seems more likely that nociception and pain originates mostly from the injury to the somatic structures of the area, rather than the viscera themselves. This nociception is predominantly conveyed by somatic afferent fibers to spinal segments, where nociceptive signals from sympathetic afferents also converge. It has been previously shown that systemically administered analgesics may potentiate the effect of other antinociceptive or analgesic agents administered neuraxially. 6,7 Therefore, in this context, the findings could be consistent with an interactive potentiation of the epidurally administered morphine by the systemically administered ketamine.
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McQuay HJ: Pre-emptive analgesia. Br J Anaesth 1992; 69: 1–3McQuay, HJ
Goto T, Marota JJ, Crosby G: Nitrous oxide induces preemptive analgesia in the rat that is antagonized by halothane. A nesthesiology 1994; 80: 409–16Goto, T Marota, JJ Crosby, G
Green T, Dockray GJ: Characterization of the peptidergic afferent innervation of the stomach in the rat, mouse and guinea-pig. Neuroscience 1988; 25: 181–93Green, T Dockray, GJ
Foreman RD: Organization of visceral input, Anesthesia: Biologic Foundations. Edited by Yaksh TL, Lynch C, Zapol WM, Maze M, Biebuyck JF, Saidman LJ. Philadelphia, Lippincott–Raven, 1997, pp 663–83
Fassoulaki A, Sarantopoulos C, Chondreli S: Systemic fentanyl enhances the spread of spinal analgesia produced by lignocaine. Br J Anaesth 1991; 67: 437–9Fassoulaki, A Sarantopoulos, C Chondreli, S
Sarantopoulos C, Fassoulaki A: Systemic opioids enhance the spread of sensory analgesia produced by intrathecal lidocaine. Anesth Analg 1994; 79: 437–9Sarantopoulos, C Fassoulaki, A