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Updated: Aug 12, 2026
The Spared Nerve Injury SNI Model of Induced Mechanical Allodynia in Mice
Published on: August 18, 2011
Synaptic Dynamics of the Feed-forward Inhibitory Circuitry Gating Mechanical Allodynia in Mice
Qun Wang1, Xiao Zhang, Xiaolan He
1From the Department of Pain Medicine, Xijing Hospital, Fourth Military Medical University, Xian, China (Q.W., X.Z., X.H., S.D., Z.J., P.L., C.L., N.G., Y.L.) the Zhejiang Key Laboratory of Organ Development and Regeneration, Institute of Life Sciences, Hangzhou Normal University, Hangzhou, China (L.Q.).
Background:
The authors' previous studies have found that spinal protein kinase C γ expressing neurons are involved in the feed-forward inhibitory circuit gating mechanical allodynia in the superficial dorsal horn. The authors hypothesize that nerve injury enhances the excitability of spinal protein kinase C γ expressing interneurons due to disinhibition of the feed-forward inhibitory circuit, and enables Aβ primary inputs to activate spinal protein kinase C γ expressing interneurons.
Methods:
Prkcg-P2A-tdTomato mice were constructed using the clustered regularly interspaced short palindromic repeats and clustered regularly interspaced short palindromic repeats-associated nuclease 9 technology, and were used to analyze the electrophysiologic properties of spinal protein kinase C γ expressing neurons in both normal conditions and pathologic conditions induced by chronic constriction injury of the sciatic nerve. Patch-clamp whole cell recordings were used to identify the nature of the dynamic synaptic drive to protein kinase C γ expressing neurons.
Results:
Aβ fiber stimulation evoked a biphasic synaptic response in 42% (31 of 73) of protein kinase C γ expressing neurons. The inhibitory components of the biphasic synaptic response were blocked by both strychnine and bicuculline in 57% (16 of 28) of neurons. Toll-like receptor 5 immunoreactive fibers made close contact with protein kinase C γ expressing neurons. After nerve injury, the percentage of neurons double-labeled for c-fos and Prkcg-P2A-tdTomato in animals walking on a rotarod was significantly higher than that in the nerve injury animals (4.1% vs. 9.9%, 22 of 539 vs. 54 of 548,P < 0.001). Aβ fiber stimulation evoked burst action potentials in 25.8% (8 of 31) of protein kinase C γ expressing neurons in control animals, while the proportion increased to 51.1% (23 of 45) in nerve injury animals (P = 0.027).
Conclusions:
The Prkcg-P2A-tdTomato mice the authors constructed provide a useful tool for further analysis on how the spinal allodynia gate works. The current study indicated that nerve injury enhanced the excitability of spinal protein kinase C γ expressing interneurons due to disinhibition of the feed-forward inhibitory circuit, and enabled Aβ primary inputs to activate spinal protein kinase C γ expressing interneurons.
