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The relationship between dorsal horn neurotransmitter content and allodynia in neuropathic rats treated with high-frequency transcutaneous electric nerve stimulation.

OBJECTIVE
To examine the relation between axon terminal neurotransmitter content in the dorsal horn and allodynia in neuropathic rats treated with high-frequency transcutaneous electric nerve stimulation (TENS).


DESIGN
A completely randomized experimental design. Two groups of rats received a chronic constriction injury to the right sciatic nerve, and 2 groups did not. The rats were either treated or not treated with TENS.


SETTING
Research laboratory.


ANIMALS
Adult male Sprague-Dawley rats (150-165g).


INTERVENTIONS
TENS was delivered daily for 1 hour to the chronic constriction injury rats or to the uninjured rats through self-adhesive electrodes applied to the skin innervated by the right dorsal rami of lumbar spinal nerves 1 to 6.


MAIN OUTCOME MEASURES
Thermal and mechanical pain thresholds were assessed bilaterally in the hind paws of all rats twice before the chronic constriction injury surgery (baseline) and then 12 days after the surgery. An analogous time frame of assessment was used for rats that did not have chronic constriction injury surgery. Thermal and mechanical allodynia were expressed as difference scores between the pain thresholds of the right and left hind paws. These values were normalized to differences that existed between the 2 paws at baseline. The amino acid content of dorsal horn axon terminals was assessed bilaterally with high-pressure liquid chromatography, and values were normalized to wet weight.


RESULTS
The mean level of thermal and mechanical allodynia did not differ between the TENS-treated and untreated rats with chronic constriction injury. However, there was a significant relation between the dorsal horn, axon terminal content of glutamate (adjusted R(2)=.45, P<.01) and glycine (adjusted R(2)=.51, P<.005) and the magnitude of mechanical allodynia present in TENS-treated chronic constriction injury rats, but not in any other group. As axon terminal glutamate and glycine decreased in the right dorsal horn and increased in the left, mechanical allodynia was reduced or absent. When this trend was reversed, mechanical allodynia was more severe. Daily TENS also reduced the mean axon terminal content of aspartate, glutamate, and glycine bilaterally in the chronic constriction injury rats from the level observed in untreated neuropathic rats (P<.05).


CONCLUSION
The variability in responsiveness of mechanical allodynia to daily TENS treatment in neuropathic rats is related to the axon terminal content of glutamate and glycine in the dorsal horn. These findings may help explain a similar variability in humans when TENS is used to treat neuropathic pain.