Abstract

IntroductionKnee 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.MethodsIn 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.ResultsFor 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.DiscussionOur 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.

Highlights

  • Knee osteoarthritis is a common disease in the elderly

  • No functional connectivity (FC) changes of Periaqueductal gray (PAG) were observed between pre-acupuncture and post-acupuncture in both patients with KOA and groups with HC

  • For dorsal raphe nuclei (RPN), no FC changes were observed between preacupuncture and post-acupuncture in two groups; no FC differences were found between patients with KOA and HC at pre-acupuncture, whereas FC in patients with KOA was significantly higher in right putamen at post-acupuncture compared with HC (Figure 2A and Table 1, p

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Summary

Introduction

Knee osteoarthritis is a common disease in the elderly. Patients suffer from long-term chronic pain and reduced life quality. 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. Acupuncture is considered an effective therapy to relieve the chronic pain of KOA [4,5,6], but the mechanism underlying its clinical efficacy is still controversial. This study aims to explore the mechanism of acupuncture treatment by investigating how acupuncture induces the functional connectivity (FC) of brains in patients with KOA. Functional MRI (fMRI) studies have investigated how the activation of PAG and RPN contributes to neural mechanisms underlying chronic pain. Another study demonstrated that dorsal RPN and ventral PAG have the potential to regulate pain by releasing dopamine and glutamate [15]

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