Y Wang1,2, F Huo1,2. 1. Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, China. 2. Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University, Xi'an, 710061, China.
Abstract
BACKGROUND: Early hyperexcitability activity of injured nerve/neuron is critical for developing sympathetic nerve sprouting within dorsal root ganglia (DRG) since lacosamide (LCM), an anticonvulsant, inhibits Na+ channel. The present study tried to test the potential effect of LCM on inhibiting sympathetic sprouting in vivo. METHODS: Lacosamide (50 mg/kg) was daily injected intraperitoneally into rats subjected to chronic compression DRG (CCD), an animal model of neuropathic pain that exhibits sympathetic nerve sprouting, for the 1st 7 days after injury. Mechanical sensitivity was tested from day 3 to day 18 after injury, and then DRGs were removed off. Immunohistochemical staining for tyrosine hydroxylase (TH) was examined to observe sympathetic sprouting, and patch-clamp recording was performed to test the excitability and Na+ current of DRG neurons. RESULTS: Early systemic LCM treatment significantly reduced TH immunoreactivity density in injured DRG, lowered the excitability level of injured DRG neurons and increased paw withdrawal threshold. These effects on reducing sympathetic sprouting, inhibiting excitability and suppressing pain behaviour were observed 10 days after the end of early LCM injection. In vitro 100 μmol/L LCM instantly reduced the excitability of CCD neurons via inhibiting Na+ current and reducing the amplitude of AP. CONCLUSIONS: All the findings suggest, for the first time, that early administration of LCM inhibited sympathetic sprouting and then alleviated neuropathic pain. SIGNIFICANCE: Early LCM administration inhibited sympathetic sprouting within DRG in CCD rats via reducing hyperexcitability of neurons. Early LCM administration suppressed neuropathic pain in CCD rats.
BACKGROUND: Early hyperexcitability activity of injured nerve/neuron is critical for developing sympathetic nerve sprouting within dorsal root ganglia (DRG) since lacosamide (LCM), an anticonvulsant, inhibits Na+ channel. The present study tried to test the potential effect of LCM on inhibiting sympathetic sprouting in vivo. METHODS:Lacosamide (50 mg/kg) was daily injected intraperitoneally into rats subjected to chronic compression DRG (CCD), an animal model of neuropathic pain that exhibits sympathetic nerve sprouting, for the 1st 7 days after injury. Mechanical sensitivity was tested from day 3 to day 18 after injury, and then DRGs were removed off. Immunohistochemical staining for tyrosine hydroxylase (TH) was examined to observe sympathetic sprouting, and patch-clamp recording was performed to test the excitability and Na+ current of DRG neurons. RESULTS: Early systemic LCM treatment significantly reduced TH immunoreactivity density in injured DRG, lowered the excitability level of injured DRG neurons and increased paw withdrawal threshold. These effects on reducing sympathetic sprouting, inhibiting excitability and suppressing pain behaviour were observed 10 days after the end of early LCM injection. In vitro 100 μmol/L LCM instantly reduced the excitability of CCD neurons via inhibiting Na+ current and reducing the amplitude of AP. CONCLUSIONS: All the findings suggest, for the first time, that early administration of LCM inhibited sympathetic sprouting and then alleviated neuropathic pain. SIGNIFICANCE: Early LCM administration inhibited sympathetic sprouting within DRG in CCDrats via reducing hyperexcitability of neurons. Early LCM administration suppressed neuropathic pain in CCDrats.