Optogenetic Activation of Peripheral Somatosensory Neurons in Transgenic Mice as a Neuropathic Pain Model for Assessing the Therapeutic Efficacy of Analgesics

被引:3
|
作者
Chen, Hao-Hao [1 ,2 ]
Mohsin, Muhammad [2 ]
Ge, Jia-Yi [1 ]
Feng, Yu-Ting [1 ]
Wang, Jing-Ge [1 ]
Ou, Yu-Sen [2 ]
Jiang, Zuo-Jie [2 ]
Hu, Bo-Ya [2 ]
Liu, Xing-Jun [1 ,2 ]
机构
[1] Nantong Univ, Sch Pharm, Nantong 226001, Jiangsu, Peoples R China
[2] Shantou Univ, Pain & Related Dis Res Lab, Med Coll, Shantou 515041, Guangdong, Peoples R China
基金
中国国家自然科学基金;
关键词
optogenetics; primary somatosensory afferents; neuropathic pain; mouse model; analgesics; advillin-Cre; GENE-RELATED PEPTIDE; DORSAL-ROOT GANGLIA; FACTOR-I RECEPTOR; CA(V)3.2 CHANNEL; ANIMAL-MODELS; MECHANISMS; ITCH; MANAGEMENT; AFFERENTS; ALLODYNIA;
D O I
10.1021/acsptsci.3c00254
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Optogenetics is a novel biotechnology widely used to precisely manipulate a specific peripheral sensory neuron or neural circuit. However, the use of optogenetics to assess the therapeutic efficacy of analgesics is elusive. In this study, we generated a transgenic mouse stain in which all primary somatosensory neurons can be optogenetically activated to mimic neuronal hyperactivation in the neuropathic pain state for the assessment of analgesic effects of drugs. A transgenic mouse was generated using the advillin-Cre line mated with the Ai32 strain, in which channelrhodopsin-2 fused to enhanced yellow fluorescence protein (ChR2-EYFP) was conditionally expressed in all types of primary somatosensory neurons (advillin(cre)/ChR2(+/+)). Immunofluorescence and transdermal photostimulation on the hindpaws were used to verify the transgenic mice. Optical stimulation to evoke pain-like paw withdrawal latency was used to assess the analgesic effects of a series of drugs. Injury- and pain-related molecular biomarkers were investigated with immunohistofluorescence. We found that the expression of ChR2-EYFP was observed in many primary afferents of paw skin and sciatic nerves and in primary sensory neurons and laminae I and II of the spinal dorsal horns in advillin(cre)/ChR2(+/+) mice. Transdermal blue light stimulation of the transgenic mouse hindpaw evoked nocifensive paw withdrawal behavior. Treatment with gabapentin, some channel blockers, and local anesthetics, but not opioids or COX-1/2 inhibitors, prolonged the paw withdrawal latency in the transgenic mice. The analgesic effect of gabapentin was also verified by the decreased expression of injury- and pain-related molecular biomarkers. These optogenetic mice provide a promising model for assessing the therapeutic efficacy of analgesics in neuropathic pain.
引用
收藏
页码:236 / 248
页数:13
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