Journal of Neuroscience, Vol 16, 730-743, Copyright © 1996 by Society for Neuroscience
Spinal cord NMDA receptors modulate peripheral immune responses and spinal cord c-fos expression after immune challenge in rats subjected to unilateral mononeuropathy
U Herzberg, MP Murtaugh, D Carroll and AJ Beitz
Department of Veterinary Pathobiology, University of Minnesota, St. Paul 55108, USA.
To characterize further the neural involvement in local immune reactions,
we evaluated the effect of intrathecal NMDA-receptor blocker dizocilpine
maleate (MK-801) on the peripheral immune response itself and on spinal
cord c-fos expression induced by the delayed-type hypersensitivity (DTH)
response. Immune challenge took place in the hind paw ipsilateral or
contralateral to an injured sciatic nerve in both previously sensitized and
immune-naive animals. An enhanced immune response was observed bilaterally
in the hind paws of animals subjected to unilateral mononeuropathy compared
with sham-operated controls. In contrast, no such enhancement was observed
when neuropathic animals were challenged in the front paws. The increased
DTH response was blocked successfully by the intrathecal administration of
an analgesic dose of MK-801. Compared with sham-operated animals, animals
subjected to unilateral mononeuropathy showed both a differential
distribution and an increase in the number of c-fos-labeled neurons in the
dorsal horn of the L3-L5 spinal cord segments after immune challenge. This
was observed irrespective of whether the challenge took place ipsilateral
or contralateral to the injured nerve. In addition to reversing the changes
in immune response, intrathecal administration of MK-801 reversed the
pattern of c-fos immunoreactivity in the spinal cord after immune challenge
in neuropathic animals. These data suggest that select groups of spinal
cord neurons participate in enhancing the peripheral immune response to a
specific antigen in neuropathic animals and that this enhancement involves
central NMDA receptors.