Electroacupuncture suppresses glucose metabolism and GLUT-3 expression in medial prefrontal cortical in rats with neuropathic pain

Abstract

Background: Accumulating evidence has demonstrated that the electroacupuncture (EA) stimulation could effectively alleviate neuropathic pain. The medial prefrontal cortex (mPFC) is a vital part of the cortical representation of pain in the brain, and its glucose metabolism is mostly affected in the progression of pain. However, the central mechanism of EA analgesia remains unclear.

Methods: Fifty-four male SD rats were equally randomized into sham surgery (Sham) group, chronic constriction injury (CCI) group and EA stimulation (EA) group. The CCI model, involving ligature of the right sciatic nerve, was established in all animals except the Sham group. EA stimulation was applied on the right side acupoints of Huantiao (GB30) and Yanglingquan (GB34) in the EA group. Paw withdrawal threshold (PWT) and paw thermal withdrawal latency (PWL) were measured. The ¹⁸ F-fluorodeoxyglucose positron emission tomography (FDG-PET) was used to evaluate glucose metabolism changes in the mPFC. The expression of glucose transporter 3 (GLUT-3) in the mPFC was determined by immune histochemistry and ELISA.

Results: Comparing with CCI groups, EA treatment was obviously reversed CCI-induced mechanical allodynia (P < 0.01), thermal hyperalgesia (P < 0.01) and the increase of glucose metabolism in the left mPFC (P < 0.05). Furthermore, EA treatment significantly decreased the protein expression of GLUT-3 in the left mPFC (P < 0.01).

Conclusions: Our results indicate that EA analgesia effect may be related to suppressing the glucose metabolism and GLUT-3 expression in the mPFC. This study could provide a potential insight into the central mechanisms involved in the analgesic effect of EA.

Keywords: Electroacupuncture; Glucose metabolism; Glucose transporter-3; Medial prefrontal cortex; Neuropathic pain.

Fig. 1

a Localization of acupoints used by electroacupuncture. b Flow chart of the experiment

Fig. 2

Effects of EA treatment in PWT and PWL of rats from the Sham, CCI and EA groups (n = 8 per group). PWT (a) and PWL (b) were recorded on the 0, 7th and 14th day after surgery. Data are presented as mean ± SD. Post hoc Tukey test ^## P < 0.01, compared with the Sham group; **P < 0.01, compared with the CCI group

Fig. 3

Before and after EA stimulation, 18F-FDG/PET/CT images of the left mPFC in rats from three groups. PET/CT image fusion: Fig a, b, c, j, k, l (coronal plane); Fig d, e, f, m, n, o (sagittal plane); Fig g, h, i, p, q, r (horizontal plane). Colour codes: Red = high, Blue = low

Fig. 4

Before and after EA stimulation, the uptake rates in the left mPFC of rats from three groups (n = 8 per group). Post hoc Tukey test, ^#P < 0.05, compared with the Sham group; ^*P < 0.05, compared with the CCI group

Fig. 5

The representative image and average optical density of GLUT-3 by the immunohistochemical detection in the left mPFC in rats from three groups. Representative image (Scale bar: 50 μm) of IHC staining of GLUT-3 in the left mPFC of rats from a Sham group (n = 6), b CCI group (n = 6), c EA group (n = 6). Positive immunoreactivity appears as brown color, and the GLUT-3 immunoreaction product was mainly expressed in the cell membrane (red arrow). d Post hoc Tukey test^# P < 0.05, compared with the Sham group. ^*P < 0.05, compared with the CCI group

Fig. 6

GLUT-3 concentrations on the left mPFC detected by ELISA in three groups (Sham, n = 4; CCI, n = 4; EA, n = 4). Post hoc Tukey test, ^#P < 0.01, compared with the Sham group, *P < 0.01, compared with the CCI group