Previous studies have demonstrated the involvement of astrocytes in the modulation of pain. The water channel aquaporin-4, which is expressed in astrocytes but not neurons, has also been demonstrated to function in sensory processing, including hearing, vision, and olfaction. In the present study, we investigated a possible role of aquaporin-4 in the processing of nociception by measuring behavioral responses to noxious stimulation in aquaporin-4 knockout mice. Pain thresholds were increased in knockout mice, when compared to wild-type mice, with thermal and chemical stimulation but not mechanical stimulation. Aquaporin-4 knockout mice presented normal locomotor activity and basal skin temperature. Likewise, the electrophysiological recordings showed a significant decrease in the number of dorsal horn neurons sensitive to noxious thermal stimuli in aquaporin-4 knockout mice. Moreover, latencies to thermal stimuli were significantly prolonged in a subset of dorsal horn wide-dynamic-range neurons. Taken together, these results suggest that aquaporin-4 plays a role in the processing of nociception.
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