Temporal and spatial determinants of sacral dorsal horn neuronal windup in relation to isoflurane-induced immobility

Robert C. Dutton, Jason M. Cuellar, Edmond I. Eger, Joseph F. Antognini, Earl Carstens

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


BACKGROUND: Windup is a progressive increase in response of dorsal horn neurons to repetitive C-fiber stimulation that may underlie temporal summation of pain. We investigated the frequency- and intensity-dependency of windup, and the effects of isoflurane and N-methyl-d-aspartate (NMDA) receptor blockade, to determine if they parallel the influence of temporal and spatial summation of noxious stimuli on anesthetic requirements. METHODS: We recorded responses of rat sacral dorsal horn neurons to 20-s trains of electrical tail stimulation at different frequencies (0.3-10 Hz) and intensities (0.8-5 × stimulus threshold) during delivery of 0.7 to 1.3 minimum alveolar anesthetic concentration isoflurane. Summed responses (area under the curve [AUC] windup), initial response, absolute windup (AUC minus 20 times the initial response), and slope of windup were quantified. RESULTS: Increases in stimulus intensity and frequency progressively increased AUC windup (P < 0.01 for both) and correlated with isoflurane concentrations required for immobility (R = 0.98 and 0.97, respectively). Increasing the isoflurane concentration significantly suppressed each measure of windup elicited by low-intensity and low-frequency, but not high-intensity and high-frequency stimulus trains. The initial response magnitude significantly correlated with slope of windup across stimulus intensities and isoflurane concentrations. The NMDA receptor antagonist MK801 significantly reduced windup (to 53%; P < 0.05) at 1 Hz. CONCLUSION: Windup of dorsal horn neurons at low stimulus intensities and frequencies increases isoflurane requirements for immobility via a NMDA receptor-dependent mechanism. At high stimulus intensities and frequencies, windup was resistant to isoflurane consistent with larger anesthetic requirements for immobility.

Original languageEnglish (US)
Pages (from-to)1665-1674
Number of pages10
JournalAnesthesia and Analgesia
Issue number6
StatePublished - Dec 2007

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine


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