Introduction: Glutamate is involved in nociceptive processes in the CNS. Although the glutamate is known to also be involved in peripheral nervous system nociception the mechanisms have not been investigated.
Methods: A nerve injury was performed on the sciatic nerve of adult male Sprague Dawley rats. Seven days post nerve injury the rats were anesthetized and the L4 and L5 dorsal root ganglia were removed and placed in a recoding chamber perfused with artificial CSF and patch clamp recordings performed on small diameter neurons (<30um) using standard methods. Glutamate receptor agonists and antagonists were applied via a 30um tip diameter pipette placed 100um from the recorded neuron.
Results: Neurons from control dorsal root ganglia responded to application of NMDA, AMPA, KA and mGluR selective agonists with inward currents and the effects of the agonists were blocked by prior application of the selective antagonists. Neurons from nerve injured ganglia had decreased action potential threshold and nerve injured neurons showed increased inward currents in response to application of selective agonists. Because there is known to be interactions between the receptor subtypes, control ganglia were incubated in DHPG (mGluR agonist) for 2 hours prior to patch clamp recording. Under these conditions AMPA selective agonists resulted in increased inward currents compared with controls.
Conclusions: These results show that peripheral nerve injury results in increased excitability of small diameter neurons and also increases the response to glutamate. mGluR receptors appear to play a key role in after nerve injury by changing the response of ionotropic glutamate receptors by an as yet undetermined mechanism. These findings open new opportunities for treating neuropathic pain using glutamate acting drugs that act only in the periphery, therefore avoiding many CNS side effects of currently used therapies.
Patient Care: These findings open new opportunities for treating neuropathic pain using glutamate acting drugs that act only in the periphery, therefore avoiding many CNS side effects of currently used therapies.
Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the importance of glutamate receptors in peripheral nerve injury, 2) Understand the interaction between different classes of glutamate receptors in the peripheral nervous system. 3) Understand the importance peripheral nerves activation in generating and maintaining neuropathic pain.