Effect of sympathetic sprouting on the excitability of dorsal root ganglion neurons and afferents in a rat model of neuropathic pain

Increased sympathetic nerve excitability has been reported to aggravate a variety of chronic pain conditions, and an increase in the number of sympathetic nerve fibers in the dorsal root ganglion (DRG) has been found in neuropathic pain (NP) models. However, the mechanism of the neurotransmitter nor...

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Veröffentlicht in:Biochemical and biophysical research communications 2022-01, Vol.587, p.49-57
Hauptverfasser: Ji, Yun, Shi, Wenjiao, Yang, Jie, Ma, Bingjie, Jin, Tian, Cao, Bingbing, Liu, Xianguo, Ma, Ke
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Sprache:eng
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Zusammenfassung:Increased sympathetic nerve excitability has been reported to aggravate a variety of chronic pain conditions, and an increase in the number of sympathetic nerve fibers in the dorsal root ganglion (DRG) has been found in neuropathic pain (NP) models. However, the mechanism of the neurotransmitter norepinephrine (NE) released by sympathetic nerve fiber endings on the excitability of DRG neurons is still controversial, and the adrenergic receptor subtypes involved in this biological process are also controversial. In our study, we have two objectives: (1) To determine the effect of the neurotransmitter NE on the excitability of different neurons in DRG; (2) To determine which adrenergic receptors are involved in the excitability of DRG neurons by NE released by sprouting sympathetic fibers. In this experiment, a unique field potential recording method of spinal cord dorsal horn was innovatively adopted, which can be used for electrophysiological study in vivo. The results showed that: Forty days after SNI, patch clamp and field potential recording methods confirmed that NE enhanced the excitability of ipsilateral DRG large neurons, and then our in vivo electrophysiological results showed that the α2 receptor blocker Yohimbine could block the excitatory effect of NE on A-fiber and the inhibitory effect on C-fiber, while the α2A-adrenergic receptor agonist guanfacine (100 μM) had the same biological effect as NE. Finally, we concluded that NE from sympathetic fiber endings is involved in the regulation of pain signaling by acting on α2A-adrenergic receptors in DRG. •After nerve injury, sympathetic nerve fibers sprouted in DRG mainly surrounded large diameter neurons.•The number of sympathetic nerve buds in DRG 14 days after SNI was small, and the cell excitability did not change after norepinephrine (NE) administration.•Our electrophysiological study demonstrated that NE is involved in the regulation of neuralgia through α2A adrenergic receptors in large diameter neurons.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2021.11.096