peripheral neuropathy in primates/pain research

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Abstract from Pain. 2004 Sep;111(1-2):151-61.

The effect of a kainate GluR5 receptor antagonist on responses of

spinothalamic tract neurons in a model of peripheral neuropathy in

primates.

Palecek J, Neugebauer V, Carlton SM, Iyengar S, Willis WD.

Institute of Physiology, Academy of Sciences, Prague, Czech Republic.

The responses of antidromically identified spinothalamic tract (STT)

neurons to mechanical and thermal stimuli were compared in anesthetized

normal and neuropathic monkeys before and after administration of a

GluR5 kainate receptor antagonist (LY382884) into the spinal cord dorsal

horn through a microdialysis fiber. Peripheral neuropathy was induced by

tight ligation of the L7 spinal nerve 13-15 days prior to the

experiment. STT neurons recorded in the animals with neuropathy showed

increased responsiveness to weak mechanical stimuli and to heating and

cooling of the skin compared to STT cells in normal animals. In both

normal and the neuropathic monkeys the responses of the STT neurons to

mechanical and thermal stimuli were attenuated by LY382884 application

in a concentration-dependent manner. Intraspinal application of LY382884

in the neuropathic animals led to a potent reduction of those responses

of the STT neurons that were aggravated by the peripheral neuropathy

(weak mechanical, heat and innocuous cooling stimuli). These results

suggest that kainate receptors are involved in synaptic activation of

STT cells in the normal state and may also play an important role in

pathological pain states such as peripheral neuropathy in primates.

Kainate receptor antagonists could thus be useful for the treatment of

certain forms of allodynia and hyperalgesia.