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. 2022 Jan 18:12:813723.
doi: 10.3389/fneur.2021.813723. eCollection 2021.

Acupuncture Enhances Dorsal Raphe Functional Connectivity in Knee Osteoarthritis With Chronic Pain

Nan Gao  1 , Haiping Shi  2 , Sheng Hu  1   3 , Bixiang Zha  2 , Aihong Yuan  2 , Jianhua Shu  3 , Yinqiu Fan  2 , Jin Bai  2 , Hongyu Xie  2 , Jingcheng Cui  4 , Xiaoxiao Wang  1 , Chuanfu Li  2 , Bensheng Qiu  1 , Jun Yang  2
Affiliations

Acupuncture Enhances Dorsal Raphe Functional Connectivity in Knee Osteoarthritis With Chronic Pain

Nan Gao et al. Front Neurol. .

Abstract

Introduction: Knee osteoarthritis is a common disease in the elderly. Patients suffer from long-term chronic pain and reduced life quality. Acupuncture has been proven to be an effective treatment for KOA. However, the neural mechanism of acupuncture is unclear, so far. Periaqueductal gray (PAG) and raphe nuclei (RPN) are essential structures associated with chronic pain in human brains. This study aims to investigate functional connectivity (FC) changes of PAG and RPN in KOA to interpret the neural mechanism of acupuncture.

Methods: In 15 patients with KOA and 15 healthy controls (HC), we acquired Visual Analog Scale (VAS) scores and resting-state fMRI images of each participant before and after acupuncture stimulation on EX-LE5 acupoint. Then, PAG and RPN were selected as seeds to perform FC analysis based on resting-state fMRI images. Finally, we compared FC patterns of PAG and RPN between patients with KOA and HC, then between pre-acupuncture and post-acupuncture. Correlations between FC values and VAS scores were calculated as well.

Results: For PAG, FC of patients with KOA was lower in the right lingual gyrus at post-acupuncture compared with HC (p <0.001, uncorrected). For dorsal RPN, FC of patients with KOA was significantly higher in right putamen at post-acupuncture compared with HC (p <0.001, corrected with FDR), and FC changes were significant between pre-acupuncture and post-acupuncture in patients with KOA. Post-acupuncture FC values between dorsal RPN and right putamen were correlated with VAS scores. For medial RPN, FC of patients with KOA was lower in the right cerebellum at post-acupuncture compared with HC (p <0.001, uncorrected), but no significant FC changes were found between pre-acupuncture and post-acupuncture in patients with KOA. FC values between medial RPN and right cerebellum were not correlated with VAS scores at pre-acupuncture and post-acupuncture.

Discussion: Our study demonstrated that acupuncture enhanced FC between dorsal RPN and the right putamen in patients with KOA, which was associated with chronic pain intensity. This result suggests that acupuncture stimulation can enhance FC between dorsal raphe and striatum, illustrating a neural mechanism that acupuncture can drive the patients' brain, with KOA, to perceive pain.

Keywords: acupuncture; chronic pain; functional connectivity; functional magnetic resonance imaging; knee osteoarthritis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Representation of seed regions. PAG, periaqueductal gray; DRPN, dorsal raphe nuclei; MRPN, medial raphe nuclei.
Figure 2
Figure 2
Group differences of FC. (A) FC of dorsal RPN of patients with KOA enhanced at post-acupuncture compared with HC. The result was corrected for FDR with p <0.001. (B) FC differences of right putamen between pre-acupuncture and post-acupuncture in KOA. (C) FC of medial RPN of patients with KOA decreased at post-acupuncture compared with HC. The result was uncorrected with p < 0.001. (D) FC differences of right cerebellum between pre-acupuncture and post-acupuncture in KOA. **: represents significant group difference with p <0.05; ns: represents no significant group difference.
Figure 3
Figure 3
Relationships between FC and pain intensity. (A) Correlation between FC of right putamen and pain intensity in KOA. (B) Correlation between FC of right cerebellum and pain intensity in KOA. Pre, pre-acupuncture; Post, post-acupuncture.
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