Reduced GABAergic neuronal activity in zona incerta causes neuropathic pain in a rat sciatic nerve chronic constriction injury model

Abstract

Purpose

The zona incerta (ZI) is below the ventral tier of the thalamus and has a strong influence selectively in higher-order thalamic relays. Although neuropathic pain has been suggested to result from reduced gamma-aminobutyric acid (GABA) and GABAergic signaling in the ZI, the mechanisms remain unclear. Here, the role of GABA and GABAergic signaling was investigated in the ZI in neuropathic pain using sciatic nerve chronic constriction injury (CCI) rats.

Materials and methods

Single-unit neuronal activity was recorded, and microdialysis was performed in the ZI of CCI rats and sham-treated rats in vivo. This study also compared ZI neuronal activity after treatment with saline, the GABA_A receptor agonist (muscimol), or the GABA_A receptor antagonist (bicuculline).

Results and conclusion

CCI rats exhibited hypersensitivity to pain as evidenced by decreased hind paw withdrawal threshold and latency. CCI rats also showed reduced GABA level and decreased neuronal activity in the ZI compared with sham-treated rats. Treatment with GABA_A receptor agonist, but not GABA_A receptor antagonist, ameliorated pain hypersensitivity and increased the firing rate (spikes/s) of ZI neurons in CCI rats.

Keywords:

• sciatic nerve injury
• chronic pain
• neuropathic pain
• zona incerta
• neural cell recording
• GABA

Supplementary material

Table S1 Firing rate in zona incerta

Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF 2014K1A3A1A21001372 and NRF2016H1D5A1908909).

Disclosure

The authors report no conflicts of interest in this work.