Differential effects of halothane and isoflurane on lumbar dorsal horn neuronal windup and excitability

Abstract

Windup of spinal nociceptive neurones may underlie temporal summation of pain, influencing the minimum alveolar concentration (MAC) of anaesthetics required to prevent movement to supramaximal stimuli. We hypothesized that halothane and isoflurane would differentially affect windup of dorsal horn neurones. We recorded 18 nociceptive dorsal horn neurones exhibiting windup to 1 Hz electrical hindpaw stimuli in rats. Effects of 0.8 and 1.2 MAC isoflurane and halothane were recorded in the same neurones (counterbalanced, crossover design). Windup was calculated as the total number of C-fibre (100-400 ms latency) plus afterdischarge (400-1000 ms latency) spikes/20 stimuli (area under curve, AUC) or absolute windup (C-fibre plus afterdischarge-20 x initial response). Increasing isoflurane from 0.8 to 1.2 MAC did not affect AUC, but increased absolute windup from 429 (62) to 618 (84) impulses/20 stimuli (P<0.05) and depressed the initial C-fibre response from 14 (3) to 8 (2) impulses (P<0.05). Increasing halothane from 0.8 to 1.2 MAC depressed AUC from 690 (79) to 537 (65) impulses/20 stimuli (P<0.05) and the initial response from 18 (2) to 13 (2) impulses (P<0.05), but absolute windup was not affected. Absolute windup was 117% greater during 1.2 MAC isoflurane compared with 1.2 MAC halothane. Windup was significantly greater under isoflurane than halothane anaesthesia at 1.2 MAC, whereas the initial C-fibre response was suppressed more by isoflurane. These findings suggest that these two anaesthetics have mechanistically distinct effects on neuronal windup and excitability.