In vivo patch-clamp analysis of hyperalgesia induced in ovarlectomized rats

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In vivo patch-clamp recordings were made from substantia gelatinosa (SG) neurons in the spinal dorsal horn to analyze a mechanism of hyperalgesia ovserved in ovariectomized rats. Noxious or non-noxious stimuli applied to the hind limb in normal rats elicited a barrage of EPSCs in all SG neurons tested and no significant difference was observed in amplitudes in both stimuli. While in OVX rats, the amplitude of noxious response was significantly larger than that of non-noxious one. Serotonin (40 μM) applied to the surface of the spinal cord depressed both responses in amplitude in normal rats, while in OVX rats, serotonin depressed only the touch-evoked responses but not pinch evoked one. Pre-treatment of OVX rats with Calcitonin prevented the augmentation of EPSCs in amplitude by noxious stimuli and the ineffectiveness of serotonin on the pinch-evoked response. Together with results obtained from slice examinations, these observations suggest that Aδ and C afferent terminals express distinct 5-HT receptor subtypes that are tonically controlled by the descending sertonergic system. In OVX rats, the receptor expressed at C afferent terminal is eliminated and results in increasing of glutamatergic transmission. After the treatment of rats with Calcitonin, the eliminated 5-HT receptor is restored. This plastic change in 5-HT receptor expression will be an underlying mechanism of hyperalgesia observed in OVX rats and its relief by Calcitonin.