Exploration of Key Brain Regions Involved in Acupuncture and Moxibustion Analgesia: An Imaging-Based Study.

Pain is a major global public health issue that significantly impacts patients’ quality of life and drives the continuous rise in global healthcare expenditures. 1 According to the Global Burden of Disease Study (GBD 2019), 2 chronic pain has become one of the leading causes of disability worldwide, with musculoskeletal pain, neuropathic pain, and migraines being the most prevalent types. Currently, approximately 20–30% of the global population suffers from chronic pain, with particularly high incidence rates among elderly individuals, women, and low-income populations. 3 The International Association for the Study of Pain (IASP) defines pain as an unpleasant sensory and emotional experience associated with actual or potential tissue damage. 4 Chronic pain not only limits patients’ mobility and daily activities but is also closely linked to mental health issues, such as anxiety, depression, and sleep disorders. Although pharmacological treatments (such as nonsteroidal anti-inflammatory drugs and opioids) play a crucial role in pain management, their long-term use is often accompanied by tolerance, dependence, and side effects, prompting researchers to explore safer and more effective non-pharmacological approaches. Understanding the mechanisms underlying pain development and its treatment is crucial for addressing this significant public health challenge. Acupuncture and moxibustion, rooted in traditional Chinese medicine’s meridian theory, involve stimulating specific acupoints to regulate qi and blood flow. Its analgesic mechanism involves multiple levels and systems, mainly including the coordinated regulation of the nervous, immune, and endocrine systems. In recent years, clinical and neurophysiological studies have shown that acupuncture and moxibustion has a significant analgesic effect in the treatment of chronic pain, musculoskeletal pain, neuropathic pain, and other diseases. 5 , 6 Studies have found that acupuncture and moxibustion can activate the endogenous analgesic pathway, promote the release of endorphins, 5-hydroxytryptamine (5-HT) and other analgesic substances, thus regulating pain perception and inflammatory response. 7 In addition, acupuncture and moxibustion can achieve analgesic effect by promoting the release of endogenous opioid peptides, up regulating the expression of local endorphins and peripheral opioid receptors, and inhibiting the effect of endogenous pain causing substances. 8 This process enhances the nervous system’s regulatory functions, ultimately providing pain relief. 9 Acupuncture and moxibustion have been approved and recommended as primary analgesic methods by the World Health Organization (WHO) and have been listed as WHO-recommended, nonpharmacological options for pain management. They have been recognized as green analgesic methods both domestically and internationally due to their advantages, including few adverse reactions, wide applicability, and fast effectiveness under standardized diagnostic and treatment criteria compared with modern drug therapy. 10 In view of opioid addiction and drug side effects, acupuncture and moxibustion has shown great potential in pain management as an alternative or adjuvant therapy. However, the mechanism underlying acupuncture and moxibustion analgesia is not completely clear, and its exploration has always been a hotspot in alternative and complementary medicine research. In recent years, neuroimaging techniques have undergone rapid advancements, significantly enhancing our comprehension of pain processing within the central nervous system (CNS). 11 These techniques offer advantages, such as being non-invasive, free of radiation, and providing high spatial resolution, making them valuable tools in modern neuroscience and acupuncture research. Through the use of neuroimaging, researchers can non-invasively observe the effects of acupuncture on brain activity and visualize specific brain regions involved in neuronal processes. This approach offers abundant visual evidence, shedding light on the central mechanisms behind acupuncture and moxibustion analgesia. The CNS response to acupuncture and moxibustion can enhance the clinical effectiveness of their analgesic properties, likely through changes in CNS functional connectivity, restoration of normal plasticity, and consequent pain relief. In this study, we aimed to analyze brain activity changes linked to acupuncture and moxibustion in the treatment of pathological pain, summarize the CNS regions activated by their analgesic effects across different pain types, explore the underlying central mechanisms of pain relief, and offer insights for future research.

The PubMed database was searched on April 15, 2024, using the keywords “acupuncture”, “analgesia”, and “neuroimaging”, and studies on regional information in the brain were selected. Without limiting the country of publication, only English literature was included, and duplicates and publications without full text availability were excluded. Two authors independently screened titles and abstracts, resolving disagreements through discussion, with the final decision being made by senior authors. To ensure comprehensive coverage, a secondary reference search was performed. After the initial screening, 1012 articles were excluded, and 65 full text articles were reviewed. Ultimately, 37 studies met the inclusion criteria. The search strategy is detailed in the Supplementary Materials . Articles were reviewed based on their abstracts and full texts and selected if they met the following criteria: original research, inclusion of patients with pathological pain, and use of neuroimaging to study brain changes resulting from acupuncture or moxibustion. Articles meeting any of the following criteria were excluded: non-acupuncture, non-pain, and non-imaging studies; non-experimental articles, such as protocols, systematic reviews, meta-analyses, and syntheses; and experimental pain research. Excel software was used to establish a literature file database to count the characteristics of the publications related to acupuncture and moxibustion analgesia research (including the publication title, corresponding author, disease name, sample size, intervention mode, acupoint selection, acupuncture and moxibustion mode, imaging method, analysis method, and activation of brain regions after acupuncture). The study selection process diagram is shown in Figure 1 . Figure 1 Flow diagram of the review process. Flow diagram of the review process.

The search was conducted on April 15, 2024, and a total of 1012 relevant records were retrieved. After title and abstract screening, 947 articles were excluded. The remaining 65 articles were fully reviewed and assessed for quality. Through discussion and consensus, 37 neuroimaging studies focusing on pathological pain were ultimately included in this review. Since 1997, there have been clinical research publications on acupuncture and moxibustion analgesia using imaging technology, and the overall number of publications has been increasing. The results are shown in Figure 2A comparison of all included studies in terms of acupoint use, control interventions, number of participants, and outcomes is presented in Table 1 . Table 1 Study Characteristics Source Diagnosis Sample Size (n) Gender (Male/Female) Age (y) Type of Intervention Acupoints Imaging Method Brain Region 12 ALBP ALBP: 28 ALBP: 17/11 - MA BL40 fMRI S1, M1, S2, frontal eye field, frontal lobe, dmPFC, SMA, HIP, PHG, AG, pACC, pMCC, DMN, insula, temporal lobe, lateral temporal cortex, THA, mammillary body, supramarginal gyrus, PAG 13 CNP TA: 66 SA: 33 - - MA SJ15, SI14, SI15, BL11, LI16 fMRI DR, thalamus, MR, parahippocampal gyrus, amygdala, insula, lingual gyrus, middle frontal gyrus, middle frontal gyrus 14 CSAP CSAP: 37 HCs: 65 CSAP: 20/17 HCs: 26/39 CSAP: 65.05 ± 7.23 HCs: 56.71 ± 5.49 MA PC6, HT5, LI5, LI6 fMRI right orbitofrontal gyrus, HIP, PHG, left calcarine, L-MCC, brain stem, ITG, THA, cerebellum crus, left cuneus 15 CSP Contra-group: 12 Ipsi-group: 8 Contra-group: 6/6 Ipsi-group: 4/4 Contra-group: 53.33 ± 5.26 Ipsi-group: 54.13 ± 7.45 MA ST38 fMRI limbic lobe, IPL, IFG, L-MFG, SMA, pACC, brain stem, THA, PoCG 16 CTS CTS: 37 HCs: 30 CTS: 7/30 HCs: 11/19 CTS: 48.5 ± 10.0 HCs: 47.5 ± 9.6 EA TW5, LV4, PC7, SP6 fMRI PAG, S1, S2, SMA, insula 17 CTS CTS: 59 CTS: 10/49 CTS: 49.1 ± 9.8 EA TW5, LV4, PC7, SP6 fMRI S1, S2, PFC, SMA, PCC, insula 18 CTS CTS: 80 HCs: 34 CTS: 15/65 HCs: 6/28 CTS: 49.3 ± 8.6 HCs: 49.7 ± 9.9 EA TW5, PC7 fMRI S1 19 CTS CTS: 10 HCs: 9 CTS: 4/6 HCs: 3/6 CTS: 51.1 HCs: 46.9 EA TW5, PC7, HT3, PC3, SI4, LI5, LI10, LU5 fMRI S1, M1 20 EMT Tret: 30 Con: 30 Tret: 0/30 Con: 0/30 Tret: 35.2 ± 4.7 Con: 36.4 ± 4.8 MA, MOX CV3 fMRI HIP 21 FM - - - EA LI11, LI4, GB34, SP6, ST36, LV3, DU20 fMRI S1, insula 22 HID HID: 20 HID: 8/12 - BA BL40, BL25, BL26 fMRI limbic lobe, insula, MFG, SFG, orbit of superior frontal gyrus, IFG, ventral anterior nucleus, ventrolateral nucleus, putamen, CG, brain stem, STG, MTG, THA, AMY 23 KOA KOA: 15 HCs: 15 KOA: 7/8 HCs: 4/11 KOA: 59.13 ± 10.27 HCs: 58.53 ± 8.15 MA EXLE5 fMRI right putamen, right lingual gyrus, striatum, RPN 24 KOA KOA: 30 KOA: 17/13 KOA: 58 ± 8 MA ST35, GB34, SP9, GB39, SP6 fMRI mFP, L-pMPFC, rACC, PAG 25 KOA Boosted Acu: 17 Standard Acu: 17 TAU: 12 Boosted Acu: 8/9 Standard Acu: 7/10 TAU: 4/8 Boosted Acu: 61.3 ± 6.9 Standard Acu: 61.2 ± 7.7 TAU: 60.1 ± 7.1 MA ST35, GB34, SP9, GB39, SP6 fMRI L-mPFC, vmPFC, Nac, rACC, PoCG, PaCG 26 KOA VA: 21 SA: 22 VA: 10/11 SA: 7/15 VA: 57 ± 7 SA: 59 ± 7 EA LI3, LI4 fMRI OPFC, R-S2, IPL, DLPFC, mPFC, putamen, ACC, insula, STG, supramarginal gyrus 27 KOA PCs: 30 - - MOX ST35 fMRI parietal lobe, frontal lobe, THA, cerebellum, occipital lobe, PreCG 28 KOA PCs: 30 PCs: 17/13 PCs: 58 ± 8 MA GB34, SP9, GB39, SP6, ST35 fMRI rFPN, mPFC, pACC, ECN 29 KOA PCs: 44 PCs: 17/13 PCs: 57.5 ± 8.3 MA ST35, GB34, SP9, GB39, SP6 fMRI MFC, HIP, PAG 30 LBP VA: Augmented: 12 Limited: 12 SA: Augmented: 13 Limited: 13 VA: Augmented: 4/8 Limited: 4/8 SA: Augmented: 5/8 Limited: 5/8 VA: Augmented: 43.00 (11.09 Limited: 34.98 (13.16) SA: Augmented: 40.02 (13.51) Limited: 39.51 (14.40) MA GV3, BL23, BL40 fMRI SPL, mPFC, VTA, AG, ACC, insula, PCU, AMY, PAG 31 LBP cLBP: 20 HCs: 10 cLBP: 10/10 HCs: 5/5 cLBP: 38.1±6.4 HCs: 38.1±6.4 MA BL23, GV3, BL40, KI3 fMRI DLPFC, mPFC, ACC, DMN, PCU 32 LBP TA: 24 SA: 26 TA: 8/16 SA: 11/15 TA: 39.0 ± 12.6 SA: 40.0 ± 13.7 MA GV3, BL23, BL40, KI3 fMRI mPFC, AG, putamen, insula, caudate nucleus 33 LBP LBP: 102 HCs: 50 LBP: 44/58 HCs: 16/34 LBP: 41.2 ± 12.0 HCs: 41.4 ± 12.3 MA GV3, BL23, BL40, KI3 fMRI S1 34 Migraine PCs: 30 PCs: 12/18 PCs: 32.87 ± 8.71 EA TE5, GB34, GB20, ST8, LI6, ST36 FDG-PET/CT OFC, MFG, HIP, PHG, AG, MCC, PCC, insula, STG, MTG, fusiform gyrus, cerebellum, PCU, supramarginal gyrus, PoCG 35 MwoA MwoA: 48 HCs: 48 MwoA: 11/37 HCs: 11/37 MwoA: 21.29 ± 1.89 HCs: 21.17 ± 0.93 MA GB34, GB40, SJ5, GB33, GB42, SJ8, ST36, ST42, LI6 MRI insular lobe, IPL, SFG, MFG, CG 36 MwoA CM: 14 HCs: 18 CM: 5/9 HCs: 9/9 CM: 42.91 ± 10.18 HCs: 38.59 ± 7.96 MA SJ5, GB20, GB8, ST8 fMRI L-SPFG, R-TPL, L-ACC, SMG, L-PCU 37 MwoA MwoA: 70 HCs: 43 MwoA: 15/56 HCs: 9/34 MwoA: 21.51 HCs: 22.23 MA GB34, GB40, SJ5, GB35, GB42, SJ8, ST36, ST42, LI6 fMRI L-MFG, L-STG, MTG, lingual gyrus, cuneus 38 MwoA MwoA: 37 HCs: 15 MwoA: 6/31 HCs: 2/13 MwoA: 37.97 ± 9.82 HCs: 34.88 ± 6.66 EA DU20, EXHN5, GB20, GB8, GB5, GB15, LI4, LR3 fMRI AG, cerebellum 39 MwoA Active acupoint: 40 Inactive acupoint: 40 Active acupoint: 12/28 Inactive acupoint: 11/29 Active acupoint: 33.35 ± 11.69 Inactive acupoint: 33.23 ± 9.73 MA SJ5, GB20, GB34, GB40, SJ22, PC7, GB37, SP3 fMRI IPL, MFG, SMA, L-HIP, AG, pACC, R-PCC, insula, brain stem, STG, ITG, MTG, THA, lingual gyrus, cerebellum, cuneus, R-PoCG 40 MwoA TA: 24 SA: 20 PCs: 0/44 TA: 33.04 ± 6.43 SA: 35.30 ± 9.43 MA GB20, GB8, PC6, SP6, LR3 fMRI R-SFG, R-IFG, R-MFG, L-ACC, R-STG, left cuneus 41 MwoA MMoA: 38 HCs: 10 MMoA: 16/22 HCs: 3/7 37.6 MA GB20, LR3, EX-HN5, GV20, EX-HN1 fMRI lingual gyrus, DMN, cerebellum 42 Sciatica Sciatica: 12 HCs: 15 Sciatica: 6/6 HCs: - Sciatica: 61.42 ± 14.84 HCs: - MA BL23, GB30, BL40, GB34, BL60, GB39, BL23, BL25, BL27, GB30, BL37, BL54, BL36, GB31, BL40, ST36, GB34, SP9, BL58, SP6, GB39, BL60, KI3, BL62 fMRI mPFC, PCC, cerebellum, L-PCU 43 PD Tret: 9 Con: 7 Tret: 4/5 Con: 5/2 Tret: 60.7 ± 6.3 Con: 70.4 ± 8.2 MA GV20, GB34, BL52 fMRI S1, insular gyrus, L-MFG, L-STG, MTG, right flocculus of cerebellum, supramarginal gyrus, PoCG, PreCG 44 PDM VA: 18 SA: 18 VA: 0/18 SA: 0/18 VA: 24.89 ± 4.59 SA: 26.13 ± 4.54 MA SP6 fMRI R-MFG, L-dACC, ACC, R-CAU, left cerebellum, cuneus, R-MFG, PAG, L-PoCG 45 PDM PDM: 29 PDM: 0/29 VA: 24.86 ± 1.75 SA: 24.53 ± 2.07 MA SP6, GB39 PET SMN, SN, DMN 46 PDM TA: 19 SA: 34 TA: 0/19 SA: 0/34 TA: 25.37 ± 2.41 SA: 24.20 ± 2.01 MA SP6 fMRI SMA, rACC, L-PreCG 47 PDM PDM: 23 HPs: 23 PDM: 0/23 HPs: 0/23 PDM: 21.74 ± 2.01 HPs: 22.26 ± 2.12 MOX CV4, CV8, SP6 fMRI L-IFG, L-PHG, MCC, pACC, L-PCC, PCU 48 TKA EA: 16 SA: 15 HCs: 32 EA: 2/14 SA: 2/13 HCs: 10/21 EA: 71.4 ± 6.1 SA: 69.4 ± 5.0 HCs: 68.8 ± 4.4 EA ST32, ST36, SP9, GB34 fMRI R-AG, L-MTG, PCU, right cuneus, MOG Abbreviations : fMRI, functional magnetic resonance imaging; PET-CT, Positron emission tomography with computed tomography; FDG-PET/CT, fluorodeoxyglucose positron emission tomography combined with computed tomography; ALBP, acute low back pain; CNP, Chronic neck pain; CSAP, chronic stable angina pectoris; CSP, chronic shoulder pain; CTS, carpal tunnel syndrome; EMT, Endometriosis; FM, fibromyalgia; HID, lumbar disc herniation; KOA, knee osteoarthritis; LBP, low back pain; MwoA, migraine without aura; PD, Parkinson’s disease; PDM, Primary dysmenorrhea; TKA, total knee arthroplasty; PFC, prefrontal cortex; OFC, orbitofrontal cortex; mPFC, medial prefrontal cortex; L-mPFC, left- medial prefrontal cortex; DLPFC, dorsolateral prefrontal cortex; L-pMPFC, left-posterior medial prefrontal cortex; SMA, supplementary motor area; SMN, the sensorimotor network; SN, salience network; DMN, default mode network; ECN, executive control network; rFPN, right-frontoparietal network; SFG, superior frontal gyrus; MFG, middle frontal gyrus; R-MFG, right- middle frontal gyrus; IFG, inferior frontal gyrus; L-IFG, left-inferior frontal gyrus; R-IFG, right-inferior frontal gyrus; PreCG, precentral gyrus; L-PreCG, left-precentral gyrus; M1, primary motor cortex; PCU, precuneus; L-PCU, left-precuneus; SPL, superior parietal lobule; IPL, inferior parietal lobule; PoCG, postcentral gyrus; L-PoCG, left-postcentral gyrus; R-PoCG, right-postcentral gyrus; S1, primary somatosensory cortex; S2, secondary somatosensory cortex; R-S2, right-secondary somatosensory cortex; AG, angular gyrus; R-AG, right-angular gyrus; STG, superior temporal gyrus; L-STG, left-superior temporal gyrus; R-STG, right-superior temporal gyrus; SFG, superior frontal gyrus; R-SFG, right-superior frontal gyrus L-SPFG, left-superior prefrontal gyrus; MTG, middle temporal gyrus; ITG, inferior temporal gyrus; MOG, middle occipital gyrus; MFG, middle frontal gyrus; L-MFG, left-middle frontal gyrus; R-MFG, right-middle frontal gyrus; HIP, hippocampus; PHG, parahippocampus; L-PHG, left-parahippocampus; CG, cingulated gyrus; CAU, caudate nucleus; Nac, nucleus accumbent; AMY, amygdala; THA, thalamus; RPN, raphe nuclei; ACC, anterior cingulate gyrus; rACC, rostral anterior cingulate cortex; L-ACC, left-anterior cingulate cortex; pACC, pregenual anterior cingulate gyrus; PCC, posterior cingulate cortex; R-PCC, right-posterior cingulate cortex; MCC, middle cingulate cortex; L-MCC, left-middle cingulate cortex; pMCC, posterior midcingulate cortex; R-TPL, right-temporal lobe; VTA, ventral tegmental area; DR, dorsal raphe nucleus; MR, median raphe nucleus. Figure 2 Annual distribution of clinical research publications in the field of acupuncture and moxibustion analgesia using imaging technology. Study Characteristics Abbreviations : fMRI, functional magnetic resonance imaging; PET-CT, Positron emission tomography with computed tomography; FDG-PET/CT, fluorodeoxyglucose positron emission tomography combined with computed tomography; ALBP, acute low back pain; CNP, Chronic neck pain; CSAP, chronic stable angina pectoris; CSP, chronic shoulder pain; CTS, carpal tunnel syndrome; EMT, Endometriosis; FM, fibromyalgia; HID, lumbar disc herniation; KOA, knee osteoarthritis; LBP, low back pain; MwoA, migraine without aura; PD, Parkinson’s disease; PDM, Primary dysmenorrhea; TKA, total knee arthroplasty; PFC, prefrontal cortex; OFC, orbitofrontal cortex; mPFC, medial prefrontal cortex; L-mPFC, left- medial prefrontal cortex; DLPFC, dorsolateral prefrontal cortex; L-pMPFC, left-posterior medial prefrontal cortex; SMA, supplementary motor area; SMN, the sensorimotor network; SN, salience network; DMN, default mode network; ECN, executive control network; rFPN, right-frontoparietal network; SFG, superior frontal gyrus; MFG, middle frontal gyrus; R-MFG, right- middle frontal gyrus; IFG, inferior frontal gyrus; L-IFG, left-inferior frontal gyrus; R-IFG, right-inferior frontal gyrus; PreCG, precentral gyrus; L-PreCG, left-precentral gyrus; M1, primary motor cortex; PCU, precuneus; L-PCU, left-precuneus; SPL, superior parietal lobule; IPL, inferior parietal lobule; PoCG, postcentral gyrus; L-PoCG, left-postcentral gyrus; R-PoCG, right-postcentral gyrus; S1, primary somatosensory cortex; S2, secondary somatosensory cortex; R-S2, right-secondary somatosensory cortex; AG, angular gyrus; R-AG, right-angular gyrus; STG, superior temporal gyrus; L-STG, left-superior temporal gyrus; R-STG, right-superior temporal gyrus; SFG, superior frontal gyrus; R-SFG, right-superior frontal gyrus L-SPFG, left-superior prefrontal gyrus; MTG, middle temporal gyrus; ITG, inferior temporal gyrus; MOG, middle occipital gyrus; MFG, middle frontal gyrus; L-MFG, left-middle frontal gyrus; R-MFG, right-middle frontal gyrus; HIP, hippocampus; PHG, parahippocampus; L-PHG, left-parahippocampus; CG, cingulated gyrus; CAU, caudate nucleus; Nac, nucleus accumbent; AMY, amygdala; THA, thalamus; RPN, raphe nuclei; ACC, anterior cingulate gyrus; rACC, rostral anterior cingulate cortex; L-ACC, left-anterior cingulate cortex; pACC, pregenual anterior cingulate gyrus; PCC, posterior cingulate cortex; R-PCC, right-posterior cingulate cortex; MCC, middle cingulate cortex; L-MCC, left-middle cingulate cortex; pMCC, posterior midcingulate cortex; R-TPL, right-temporal lobe; VTA, ventral tegmental area; DR, dorsal raphe nucleus; MR, median raphe nucleus. Annual distribution of clinical research publications in the field of acupuncture and moxibustion analgesia using imaging technology. The 37 reviewed articles involved a total of 14 diseases, including eight articles on migraine without aura; seven articles on knee osteoarthritis; five articles on lower back pain; four articles each on carpal tunnel syndrome and primary dysmenorrhea; and one article each on sciatica, lumbar disc herniation with lower back and leg pain, chronic shoulder pain, chronic neck pain, stable angina, Parkinson’s disease, fibromyalgia, endometriosis, and acute pain after knee replacement surgery. The proportion of diseases is shown in Figure 3 . Figure 3 Proportion of diseases subjected to acupuncture and moxibustion analgesia research using imaging technology. Proportion of diseases subjected to acupuncture and moxibustion analgesia research using imaging technology. A total of 34 studies employed acupuncture stimulation methods, with 22 utilizing manual acupuncture and 12 opting for electroacupuncture as the intervention. Only two studies chose moxibustion as the treatment, and just one study combined both acupuncture and moxibustion. The specific selection of acupoints for pathological conditions is presented in Table 2 . Table 2 Literature Research of the Disease Details and Acupoint Selection in the Clinical Research Field of Acupuncture and Moxibustion Analgesia Based on Imaging Technology Investigated Diseases Selection of Acupoints Migraine TE5, GB34, GB20, ST8, LI6, GB40, SJ5, GB33, GB42, SJ8, ST36, ST42, GB35, GB8, DU20, EXHN5, GB5, GB15, LI4, LR3, SJ22, PC7, GB37, SP3, PC6, SP6, LR3, GV20, EX-HN1 Knee osteoarthritis EXLE5, ST35, GB34, SP9, GB39, SP6, LI3, LI4 Low back pain BL40, GV3, BL23, KI3 Carpal tunnel syndrome TW5, LV4, PC7, SP6, GB34, KD3, SP5, HT3, PC3, SI4, LI5, LI10, LU5 Primary dysmenorrhea SP6, GB39, CV4, CV8 Chronic neck pain SJ15, SI14, SI15, BL11, LI16 Chronic stable angina pectoris PC6, HT5, LI5, LI6 Chronic shoulder pain ST38 Endometriosis-associated pain CV3 Fibromyalgia LI11, LI4, GB34, SP6, ST36, LV3, DU20, HT7 Lumbar disc herniation BL40, BL25, BL26 Sciatica BL23, GB30, BL40, GB34, BL60, GB39, BL23, BL25, BL27, GB30, BL37, BL54, BL36, GB31, BL40, ST36, GB34, SP9, BL58, SP6, GB39, BL60, KI3, BL62 Parkinson’s disease GV20, GB34, BL52 Total knee arthroplasty ST32, ST36, SP9, GB34 Literature Research of the Disease Details and Acupoint Selection in the Clinical Research Field of Acupuncture and Moxibustion Analgesia Based on Imaging Technology This review categorized and summarized the clinical study results based on the corresponding brain structures. The frequency of acupuncture and moxibustion activation of brain regions was 51 times in the frontal lobe, 39 times in the limbic lobe, 36 times in the parietal lobe, 25 times in the temporal lobe, 15 times in the occipital lobe, 13 times in the insular lobe, 11 times in the basal nucleus, 9 times in the cerebellum, 9 times in the thalamus, 6 times in the aqueduct gray matter of the mesencephalic island, 7 times in the brainstem, and one time each in the hypothalamus and ventral dorsal tegmental area. The detailed frequency of activated brain lobes is shown in Figure 4A-F . Figure 4 Total frequency of brain region appearances in articles included in the analysis. Notes : ( A ) The proportion of brain regions activated in the frontal lobe. ( B ) The proportion of brain regions activated in the limbic lobe. ( C ) The proportion of brain regions activated in the parietal lobe. ( D ) The proportion of brain regions activated in the temporal lobe. ( E ) The proportion of brain regions activated in the occipital lobe. ( F ) The proportion of brain regions activated in the basal ganglia. ( G ) The total frequency of brain region appearances in the articles. Abbreviations : PFC, prefrontal cortex; SMA, supplementary motor area; SFG, superior frontal gyrus; MFG, middle frontal gyrus; IFG, inferior frontal gyrus; PreCG, precentral gyrus; M1, primary motor cortex; PCU, precuneus; SPL, superior parietal lobule; IPL, inferior parietal lobule; PoCG, postcentral gyrus; S1, primary somatosensory cortex; S2, secondary somatosensory cortex; AG, angular gyrus; STG, superior temporal gyrus; MTG, middle temporal gyrus; ITG, inferior temporal gyrus; MOG, middle occipital gyrus; HIP, hippocampus; PHG, parahippocampus; CG, cingulated gyrus; CAU, caudate nucleus; Nac, nucleus accumbent; AMY, amygdala. Total frequency of brain region appearances in articles included in the analysis. For analgesia, acupuncture was used more frequently than moxibustion. Acupuncture mainly activated the frontal lobe, parietal lobe, limbic lobe, temporal lobe, insular lobe, occipital lobe, basal nucleus, cerebellum, dorsal thalamus, periaqueductal gray matter (PAG), brainstem, hypothalamus, and ventral dorsal tegmental area ( Figure 4G ). The brain areas activated by hand acupuncture and electroacupuncture mostly overlapped. Moxibustion mainly activated the limbic frontal lobe, parietal lobe, occipital lobe, thalamus, and cerebellum ( Figure 4G ). These findings indicate that, while different intervention methods activate specific brain regions, they also share common areas of activation. Pain can be categorized as either acute or chronic, depending on the duration of the condition. In the current review, acute pain diseases included acute low back pain, 12 acute pain after total knee arthroplasty, 48 and acute migraine without aura. 34 Chronic pain diseases included migraine without aura, 35–41 knee osteoarthritis, 23–29 carpal tunnel syndrome, 16–19 chronic low back pain, 30–33 Parkinson’s disease, 43 chronic stable angina pectoris, 14 a herniated lumbar disc with low back and leg pain, 22 non-acute sciatica, 42 chronic shoulder pain, 15 fibromyalgia, 21 chronic neck pain, 13 primary dysmenorrhea 44–47 and endometriosis. 20 Both acute and chronic pain engage multiple brain regions, including the temporal lobe, limbic system (such as the insula and amygdala), frontal lobe, parietal lobe, and cerebellum. These areas are crucial for pain perception, emotional regulation, and motor responses associated with pain. Notably, both types of pain strongly activate parts of the limbic system, such as the insula and amygdala, highlighting the emotional processing of pain. However, acute pain primarily activates regions involved in sensory and motor processing, like the parietal lobe and primary somatosensory cortex. In contrast, chronic pain predominantly engages areas linked to pain evaluation, processing, and attention, such as the frontal lobe and insula. Additionally, chronic pain activates regions within the basal ganglia, including the striatum, which may be related to non-pain symptoms like movement disorders. Chronic pain also shows broader activation within the limbic system, including the hippocampus and amygdala, indicating a possible role in emotional memory processing ( Figure 5A and B ). Figure 5 Brain response to acupuncture treatment for different pain types. Notes : ( A ) Brain regions activated after acupuncture and moxibustion for acute pain. ( B ) Brain regions activated after acupuncture and moxibustion for chronic pain. ( C ) Brain regions activated after acupuncture and moxibustion for visceral pain. ( D ) Brain regions activated after acupuncture and moxibustion for physical pain. Brain response to acupuncture treatment for different pain types. Based on the location of pain in the body, it can be classified as visceral or somatic pain. In this review, primary dysmenorrhea 44–47 and endometriosis 20 were included in the analysis of visceral pain. Acute low back pain, 12 acute pain after total knee arthroplasty, 48 acute migraine without aura, 34 Migraine without aura, migraine without aura, 35–41 knee osteoarthritis, 23–29 carpal tunnel syndrome, 16–19 chronic low back pain, 30–33 Parkinson’s disease, 43 chronic stable angina pectoris, 14 a herniated lumbar disc with low back and leg pain, 22 non-acute sciatica, 42 chronic shoulder pain, 15 fibromyalgia, 21 chronic neck pain, 13 were included in the analysis of somatic pain. Both visceral and somatic pain activated several brain regions, including the insular cortex, cerebellum, limbic system, basal ganglia, and the frontal, parietal, temporal, and occipital lobes. However, visceral pain activated more regions in the medial aspect of the limbic system, including the PAG matter, whereas somatic pain activated more regions in the motor and somatosensory cortex. Visceral pain showed a less widespread activation in the brain, mainly concentrated in the cortex and limbic system. In contrast, somatic pain had a broader activation range, including the cortex, limbic system, and deep structures, such as the thalamus and hypothalamus ( Figure 5C and D ). In this study, both migraine and knee osteoarthritis were treated with acupuncture and moxibustion, making them suitable for comparing different brain region responses to these two treatment methods. For migraine, electroacupuncture and hand acupuncture both activated the frontal lobe, parietal lobe, temporal lobe, insular lobe, basal ganglia, and other cortical areas and subcortical structures related to pain, attention, and motor functions. In addition, electroacupuncture activated the limbic system and thalamus. Electroacupuncture focused more on the frontal lobe, temporal lobe, and other anterior regions, whereas hand acupuncture focused more on the parietal lobe, thalamus, and other posterior regions ( Figure 6A ). Figure 6 Brain region activation in response to different treatment methods used for the same disease. Notes : ( A ) Differences in brain areas responding to electroacupuncture and hand-acupuncture in migraine. ( B ) Differences in brain regions responding to acupuncture and moxibustion in knee osteoarthritis. Brain region activation in response to different treatment methods used for the same disease. For knee osteoarthritis, acupuncture and moxibustion co-activated areas including the frontal lobe, parietal lobe, occipital lobe, and thalamus. However, acupuncture-induced activation was more pronounced in the anterior regions, such as the prefrontal lobe, frontoorbital gyrus, and anterior cingulate gyrus, whereas moxibustion-induced activation was more pronounced in the middle and posterior regions, such as the parietal lobe, putamen, and thalamus ( Figure 6B ). The articles included in this review were categorized based on the imaging methods used. The majority employed functional magnetic resonance imaging (fMRI) to investigate the mechanisms of acupuncture analgesia, while only two studies utilized positron emission tomography (PET).

Acupuncture and moxibustion are distinctive therapeutic methods in traditional Chinese medicine. However, current research on their mechanisms, aided by imaging technology, is notably imbalanced. The academic focus has heavily favored acupuncture over moxibustion, leading to a limited scientific understanding of moxibustion’s therapeutic mechanisms. This research bias has resulted in a deeper exploration of acupuncture’s CNS effects, covering various physiological and neurologic aspects. Yet, as moxibustion is an integral part of acupuncture therapy, its mechanisms also warrant thorough investigation within modern medical contexts. Researchers are encouraged to use imaging technology to explore moxibustion’s unique mechanisms, aiming to fully uncover the potential and value of acupuncture and moxibustion in contemporary medicine. This study provides a comprehensive analysis of the central mechanisms underlying acupuncture and moxibustion analgesia, highlighting the significant brain regions affected by these traditional Chinese medicine practices. Neuroimaging studies indicate that acupuncture predominantly activates the frontal lobe, limbic system, parietal lobe, and other areas crucial for pain perception, emotional regulation, and cognitive function. Both acupuncture and moxibustion stimulate the ACC and PFC, which are essential in modulating pain and emotional responses. Moreover, the activation of the brainstem and PAG highlights the role of the endogenous opioid system in pain relief. These findings underscore the potential of acupuncture and moxibustion as effective non-pharmacological approaches for pain management and offer valuable insights for future research and clinical applications.

This review analysed the literature on changes of brain function associated with acupuncture and moxibustion analgesia determined using imaging technology. Acupuncture and moxibustion exert their analgesic effects by stimulating different areas of the CNS and modulating neurotransmitters, signaling pathways, and immune responses. 49 Neuroimaging studies have demonstrated that acupuncture influences various brain regions involved in pain perception, emotional regulation, and cognitive functions. The following sections highlight key findings from neuroimaging research on the brain areas affected by acupuncture analgesia. According to this study, the frontal lobe is frequently activated by acupuncture. The prefrontal cortex (PFC) is responsible for executive functions, such as working memory, decision-making, and emotional regulation. 50 Acupuncture and moxibustion have been found to alter the functional connectivity of the PFC, thereby reducing cognitive and emotional responses to pain. At the molecular level, this effect is linked to the modulation of neurotrophic factors, like the brain-derived neurotrophic factor (BDNF), which plays a crucial role in promoting neuronal survival and synaptic plasticity. 51 Changes in the levels of BDNF and other neurotrophic factors contribute to the PFC’s role in pain and stress reduction. 11 Moreover, the primary somatosensory cortex (S1) is a key region within the brain responsible for processing sensory information, including pain signals. 52 Neuroimaging studies have revealed that acupuncture can modulate the activity of S1, resulting in altered pain perception. 16 , 43 This modulation is associated with alterations in synaptic activity and neurotransmitter release, particularly involving glutamate and gamma-aminobutyric acid (GABA). 53 , 54 Glutamate is typically associated with excitatory signals, which increase the chances that a neuron will fire, while GABA serves as an inhibitory neurotransmitter, decreasing neuron firing. The balance between these neurotransmitters is essential for proper brain function and pain processing. 55 In the context of acupuncture, altering the activity of glutamate and GABA might modify how intensely pain is felt. The S1’s role in encoding the intensity and location of pain makes it a crucial target for these therapies. Acupuncture and moxibustion can also affect pain-related cerebral cortex areas, such as the motor cortex and sensory cortex, change their functional connections, and reduce pain perception and transmission. 56 The limbic system, including the anterior cingulate cortex (ACC), insula, and hippocampus, is another critical area influenced by acupuncture. The ACC plays a central role in emotional processing and pain perception. 57 Acupuncture and moxibustion have been shown to alter the functional connectivity of the ACC, leading to a reduction in the emotional and cognitive components of pain. 24 , 47 Molecularly, this effect is associated with the regulation of neurotransmitters, such as serotonin and dopamine, which are involved in mood and pain modulation. 58 , 59 The insula integrates sensory and affective aspects of pain. 60 The hippocampus, associated with memory and emotional responses, 61 also shows altered activity patterns under acupuncture and moxibustion. 20 These alterations in the limbic system emphasize acupuncture’s capacity to regulate both the sensory and emotional aspects of pain, offering a more holistic approach to pain management. Acupuncture also affects other brain regions, including the parietal, temporal, and occipital lobes, basal ganglia, cerebellum, thalamus, and brainstem. Within the parietal lobe, the postcentral gyrus (PoCG) and superior parietal lobule (SPL) are components of the somatosensory cortex, playing a crucial role in processing sensory information and localizing pain. 62 The temporal lobe regions, such as the superior temporal gyrus (STG) and middle temporal gyrus (MTG), are involved in sensory integration and memory, contributing to the overall perception of pain. 63 The activation of the occipital lobe suggests a potential integration of visual and sensory information. Moreover, the basal ganglia, particularly the caudate nucleus and putamen, play a vital role in motor control and pain modulation. 64 , 65 The cerebellum’s role in motor coordination and the thalamus’s function as a relay center for sensory signals further emphasize acupuncture’s comprehensive impact on the brain. 66 The brainstem, particularly the PAG, is involved in the endogenous pain modulation system, facilitating the release of endogenous opioids and contributing to pain relief. 67 Endogenous opioid peptides are important analgesic neurotransmitters, which can inhibit pain generation and transmission. Moreover, the thalamus is also a key component of the descending inhibitory system. 68 Therefore, acupuncture inhibits pain transmission and perception by activating endogenous analgesic systems in these regions. 69 The brain regions influenced by acupuncture are primarily concentrated in the default mode network and basal ganglia. The default mode network is linked to spontaneous thought and introspection, while the basal ganglia are involved in motor control and conditioned learning. 70 , 71 This suggests that acupuncture not only modulates brain regions directly associated with pain, but also affects higher brain functions more broadly. This may be related to the overall acupuncture-induced regulation. In addition to physiological regulation, acupuncture and moxibustion affect the psychological state of individuals, reducing anxiety and depression, increasing pleasure, and diminishing the degree and duration of pain. This highlights the complex interaction between physiological and psychological processes in pain management through acupuncture and moxibustion. The study analyzed and compared acute, chronic, somatic, and visceral pain, demonstrating that acupuncture and moxibustion activate specific brain regions depending on the nature of the experienced pain. Both acute and chronic pain activated certain common brain regions, but chronic pain affected a wider range of brain regions because of its persistence, complexity, and accompanying symptoms. In particularly, chronic pain involved more areas of the PFC, limbic system, and basal ganglia, further underscoring the widespread effects of chronic pain on the CNS. Chronic pain differs from acute pain with regards to the implicated neurologic mechanisms, mainly related to the duration of pain and extent of its effects on the nervous system. Acute pain is usually a sudden, short-lived pain experience, in which pain signals are transmitted from injured tissues to the CNS, activating brain regions associated with pain perception and triggering corresponding physiological and behavioral responses. 72 Pain caused by injury or illness is considered chronic if it lasts for more than three months. 1 Chronic pain has more complex and persistent manifestations and symptoms than acute pain. 73 At the same time, chronic pain is often accompanied by numerous comorbid symptoms and conditions, such as mood disorders and cognitive decline. 74 From a neurologic perspective, pain signals triggered by chronic pain activate more brain regions, including the PFC, limbic system, and basal ganglia. These brain regions play important roles in pain perception, emotional regulation, and attention control. For example, the PFC is involved in the cognitive processing and emotional regulation of pain, 75 the limbic system in the attentional and emotional responses to pain, 76 and the basal ganglia in the motor and behavioral responses to pain. 77 Chronic pain not only affects the CNS at the perceptual and cognitive levels, but also induces a wide range of physiological and psychological changes. Long-term pain stimulation can cause plasticity changes in the CNS, making the transmission of pain signals more sensitive and resulting in increased persistence and prolonged duration of pain. 78 Therefore, the therapeutic approach to chronic pain needs to consider its extensive effects on the CNS. Both somatic and visceral pain involve the same areas of the brain. However, visceral pain and somatic pain differ in the extent and focus of activation of specific brain regions due to their different locations and symptoms. 79 This distinction underscores the intricate nature of pain processing within the brain. The current study suggests that visceral pain is more likely to trigger the activation of brain regions associated with mood and emotion, 80 which may explain why visceral pain is often accompanied by strong emotional responses. In contrast, somatic pain tends to activate areas associated with sensory perception and movement. These findings underscore the intricate and multifaceted nature of pain processing in the brain. Different types of pain activate distinct brain regions, and by assessing brain changes in patients with various pain conditions treated with acupuncture and moxibustion, we can reveal disease-specific neuromodulation effects. The above results indicate that differences in activated brain regions during acupuncture and moxibustion treatment may reflect characteristics of different pain types and disease specificity. The high correlation of common brain regions reflects the stability of acupuncture and moxibustion regulation of brain functional connectivity. Electroacupuncture and manual acupuncture were found to activate a wider range of sensory cortex areas, including the parietal, temporal, and occipital lobes, which are closely linked to somatosensory processing and pain perception. However, moxibustion activated more prominently the limbic system and occipital lobe, possibly due to the mild heat sensation associated with moxibustion. These findings suggest that acupuncture and moxibustion exhibit distinct patterns of brain function regulation, providing unique perspectives for exploring their mechanisms in pain treatment. According to this study, medical imaging techniques have been used in clinical research on acupuncture analgesia since 1997. With the continuous development of medical imaging technology, an important milestone occurred in 2014, which was the first publication peak. This indicates that advances in medical imaging techniques have facilitated in-depth research into the mechanism of acupuncture analgesia. fMRI has high and comprehensive spatial and temporal performance and can provide detailed imaging information to help researchers observe brain changes during acupuncture and moxibustion treatment. However, limitations of current technology have impeded the progress in visualizing acupuncture and moxibustion analgesia mechanisms. Nevertheless, with the continuous advances of medical imaging techniques, we believe that we can overcome these limitations in the future and further reveal the mechanism of acupuncture and moxibustion analgesia.

The study revealed that acupuncture produces a notable analgesic effect. However, the analysis was constrained by a small sample size, with only 37 included articles, and the range of examined disease types was relatively limited. Variations in stimulation parameters may also have influenced changes in functional connectivity. Additionally, the control group design had certain limitations. Future studies should aim to increase the sample size, expand the range of disease types, standardize stimulation parameters, and optimize control group design to enhance the study’s reliability.