| Summary: | We examined wind-up of the nociceptive flexor withdrawal responses in diabetic mice that had developed tactile allodynia after treatment with streptozotocin (STZ). In control and STZ-treated mice, simultaneous activation of Aδ- and C-fibers by electrical stimuli at C-fiber intensity delivered to the ventral aspect of the toe elicited a biphasic withdrawal reflex composed of short- and long-latency movements of the ipsilateral hind paw that were respectively mediated by activation of Aδ- and C-fibers. There were no significant differences between control and diabetic mice in the activation threshold of each reflex movement or the amplitude of reflexes elicited by various stimulus intensities. However, a repetitive conditioning stimulus (CS) elicited significantly greater wind-up of the C-fiber-mediated movement and early saturation of wind-up in diabetic mice. In both control and diabetic mice, the CS elicited no or occasionally slight wind-up of the Aδ-fiber-mediated movement. Moreover, post-CS facilitation, which reflects the prolonged excitability increase, was observed in both Aδ-fiber- and C-fiber-mediated movements of control mice, whereas significant post-CS facilitation was only obtained in the C-fiber-mediated movement of diabetic mice, which may reflect supraspinal descending influences. Such changes in the excitability of spinal neurons in diabetic mice may represent some aspect of painful diabetic neuropathy. Keywords:: diabetes, allodynia, flexor reflex, wind-up, C-fiber
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