Upregulation of spinal glutamate receptors in chronic pain.

Recent studies indicate that glutamate binding to N-methyl-D-aspartate receptors in the spinal cord is involved in triggering the development of chronic pain However, the processes which directly underlie the increased pain remain unclear. Here we report that, following peripheral nerve injury (ligation of the sciatic nerve) in the rat, there is an increase in immunoreactive labelling of non-N-methyl-D-asparatate, AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate), glutamate receptors in the superficial laminae of the lumbar spinal cord ipsilateral to the ligation. The increase in AMPA receptor expression peaks 14 days after nerve ligation and decreases 35 days post-ligation, corresponding to the time-course of heightened sensitivity to mechanical and thermal noxious stimuli (hyperalgesia) induced by the ligation. Given evidence that AMPA receptors in the superficial laminae mediate fast nociceptive transmission in the spinal cord, our findings suggest that an upregulation of spinal AMPA receptors contributes to hyperalgesia following peripheral nerve injury.