Enhanced wind-up of the C-fiber-mediated nociceptive flexor reflex movement following painful diabetic neuropathy in mice

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 Adelta- 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 Adelta- 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 Adelta-fiber-mediated movement. Moreover, post-CS facilitation, which reflects the prolonged excitability increase, was observed in both Adelta-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.