Impaired formalin-evoked changes of spinal amino acid levels in diabetic rats

To investigate mechanisms by which diabetes alters sensory processing, we measured levels of amino acid neurotransmitters in spinal dialysates from awake, unrestrained control and diabetic rats under resting conditions and following hind paw formalin injection. Under resting conditions, glutamate concentrations in spinal dialysates were significantly (P < 0.05) decreased in diabetic rats compared to those of control rats whereas aspartate, taurine, glycine and citrulline remained unchanged and GABA was significantly (P < 0.05) increased. Noxious stimulation of the hind paw by subcutaneous injection of 0.5% formalin into the dorsum caused a defined flinching behavior in the afflicted paw, and the amount of flinching was significantly (P < 0.05) greater in diabetic rats than in controls. Paw formalin injection significantly (P < 0.05) increased dialysate levels of glutamate, aspartate, taurine, glycine and citrulline by 3- to 4-fold above basal in both control and diabetic rats. The concentration of glutamate in dialysate samples collected immediately after paw formalin injection remained significantly (P < 0.05) lower in diabetic rats compared to those in controls. Formalin injection did not alter dialysate GABA concentrations in control rats, whereas in diabetic rats there was an increase of 151 ± 15% above basal levels. These findings indicate that the selective depression of basal and stimulus-evoked glutamate levels in the spinal cord of diabetic rats occurs in parallel with elevated spinal GABA levels. Because increased pain-associated behavior is accompanied by an attenuated spinal glutamate spike following paw formalin injection, hyperalgesia in diabetic rats does not appear to be secondary to enhanced glutamatergic input to the spinal cord.