Acute inhibition of signalling phenotype of spinal GABAergic neurons by tumour necrosis factor-alpha

作者：Zhang Haijun; Dougherty Patrick M^*

来源：The Journal of Physiology, 2011, 589(18): 4511-4526.

DOI：10.1113/jphysiol.2011.215301

Spinal application of TNF alpha induces both allodynia and hyperalgesia, and at least part of the pronociceptive effects of TNF alpha have been suggested as due to the impaired function of spinal inhibitory neurons (disinhibition). The present study explores the effects of TNF alpha on the signalling phenotype of spinal GABAergic neurons identified in transgenic mice expressing green fluorescent protein at the glutamic acid decarboxylase 67 (GAD67) promoter. Acute application of TNF alpha directly inhibits the excitability of a subset of GAD67(+) spinal neurons. TNF alpha-induced inhibition was dependent on the activation of p38 mitogen-activated protein kinase (MAPK) within these GAD67(+) neurons. TNF alpha receptor 1 (TNFR1) but not receptor 2 (TNFR2) was identified on spinal GAD67(+) neurons, suggesting that TNF alpha signals through TNFR1. Voltage-clamp recordings of GAD67(+) neurons indicated that the inhibitory effect of TNFa was through suppression of the hyperpolarization-activated cation current (I(h)). This study defines a novel mechanism of spinal disinhibition mediated by a TNF alpha-TNFR1-p38 pathway within GABAergic inhibitory interneurons.

• 出版日期2011-9-15