Altered thalamic neurotransmitters metabolism and functional connectivity during the development of chronic constriction injury induced neuropathic pain

Zhifu Wang,Long Li,Jing Tao,Xiangmei Yu,Weilin Liu,Shengxiang Liang,Minguang Yang,Sheng Huang

doi:10.1186/s40659-020-00303-5

Zhifu Wang, Long Li + Show 6 more

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https://doi.org/10.1186/s40659-020-00303-5

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Abstract

BackgroundTo investigate the thalamic neurotransmitters and functional connections in the development of chronic constriction injury (CCI)-induced neuropathic pain.MethodsThe paw withdrawal threshold was measured by mechanical stimulation the right hind paw with the von frey hair in the rats of CCI-induced neuropathic pain. The N-acetylaspartate (NAA) and Glutamate (Glu) in thalamus were detected by magnetic resonance spectrum (MRS) process. The thalamic functional connectivity with other brain regions was scanned by functional magnetic resonance image (fMRI).ResultsThe paw withdrawal threshold of the ipsilateral side showed a noticeable decline during the pathological process. Increased concentrations of Glu and decreased levels of NAA in the thalamus were significantly correlated with mechanical allodynia in the neuropathic pain states. The thalamic regional homogeneity (ReHo) decreased during the process of neuropathic pain. The functional connectivity among the thalamus with the insula and somatosensory cortex were significantly increased at different time points (7, 14, 21 days) after CCI surgery.ConclusionOur study suggests that dynamic changes in thalamic NAA and Glu levels contribute to the thalamic functional connection hyper-excitation during CCI-induced neuropathic pain. Enhanced thalamus-insula functional connection might have a significant effect on the occurrence of neuropathic pain.

Highlights

Neuropathic pain due to injuries or lesions in the peripheral nervous system is always accompanied by allodynia, hyperalgesia, and even numbness [1, 2]
Changes in mechanical threshold on the days 0, 7, 14, 21 after constriction injury (CCI) surgery As illustrated in Fig. 1, compared to the sham group, the paw withdrawal threshold of the ipsilateral side showed a prominent decline in rats on day 7 (5.48 ± 0.56 g vs 11.80 ± 1.57 g, **P < 0.01), day 14 (3.53 ± 0.70 g vs 11.67 ± 1.68 g, **P < 0.01), and day 21 after CCI surgery (5.26 ± 0.78 g vs 11.13 ± 0.67 g, **P < 0.01)
CCI-induced paw withdrawal threshold decrease compared with the sham group, two-way repeated Analysis Of Variance (ANOVA), F1, 51 = 206.166, P < 0.001, post hoc Tukey test: **P < 0.01

Summary

Introduction

Neuropathic pain due to injuries or lesions in the peripheral nervous system is always accompanied by allodynia, hyperalgesia, and even numbness [1, 2]. Previous studies have revealed that aberrant activity and neurotransmitter alterations in the central nervous system are the significant pathological mechanism in a variety of pain models [8,9,10]. A variety of in vivo studies have demonstrated that thalamic NAA alteration is critical in the development of chronic pain. Glutamate (Glu) levels have been reported to distinguishing healthy individuals from patients [11, 12]. Due to their magnetic sensitivity and mass enrichment in vivo, proton nuclei are widely applied in magnetic resonance spectroscopy studies. To investigate the thalamic neurotransmitters and functional connections in the development of chronic constriction injury (CCI)-induced neuropathic pain

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