Knowledge mapping of acupoint sensitization and acupoint specificity: a bibliometric analysis.

Objective: The relationship between acupoint sensitization and acupoint specificity is a topic of significant interest in acupuncture research. Numerous clinical studies have demonstrated that needling pain sensitive acupoints yields superior therapeutic outcomes compared to traditional acupoints, particularly in the context of pain disorders. However, there is a lack of bibliometric analysis in acupuncture area. Therefore, the objective of this study is to offer a comprehensive overview of the knowledge structure and research hotspots pertaining to acupoint sensitization and acupoint specificity. Methods: The search for publications pertaining to acupoint sensitization and acupoint specificity was conducted in the Web of Science Core Collection (WoSCC) database from its inception until August 11, 2023. Subsequently, bibliometric analyses were carried out using VOSviewer, CiteSpace, R software (Bibliometrix package), and GraphPad Prism software. Results: This study includes 4,940 articles from 72 countries, with China and the United States being the leading countries. The number of publications related to acupoint sensitization and specificity has been increasing annually. Major research institutions involved in this field include the Shanghai University of Traditional Chinese Medicine, Kyung Hee University, Beijing University of Chinese Medicine, Chinese Academy of Chinese Medical Sciences, and China Medical University, among others. "Evidence-based Complementary and Alternative Medicine" is the most popular journal in acupuncture field, and "PAIN" is the most co-cited journal. Publications are contributed by 20,325 authors from all over the world, with Wu Huangan, Fang Jianqiao, Lin Yi-Wen, Liu Huirong, and Chen Rixin having published the most articles. Han Ji-Sheng is the most cited author in this research area. The main directions include the study of temperature specificity of acupoints, the diagnosis of acupoint sensitization diseases, and the study of the mechanism of acupoint sensitization. The most listed keywords in recent years are "TRPV1," "signaling pathway," and "diagnosis." Conclusion: This is the first bibliometric study to comprehensively summarize research trends and advances in acupoint sensitization and acupoint specificity, and the information highlights recent research preliminary and main directions that serve as a reference for acupoint sensitization and acupoint specificity research.

Peripheral neural mechanism of visceral pain and acupoint sensitization in 2, 4, 6-trinitrobenzene sulfonic acid-induced colitis model mice. / ç»“è‚ ç‚Žæ¨¡åž‹å°é¼ å† è„ç—›åŠç©´ä½æ•åŒ–çš„å¤–å‘¨ç¥žç»æœºåˆ¶æŽ¢è®¨.

OBJECTIVES: To explore the neural mechanism of visceral pain and related somatic (acupoints) sensitization by using in vivo calcium imaging of dorsal root ganglia (DRG) neurons. METHODS: Eight BALB/c mice were randomly divided into control and model groups, with 4 mice in each group. The colitis model was induced by colorectal perfusion of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS) once daily for 7 days. Mice of the control group received colorectal perfusion of normal saline once daily for 7 days. The location and area of the somatic neurogenic inflammation (cutaneous exudation of Evans blue ï¼»EBï¼½) of the 2 groups of mice were observed after intravenous injection of EB. For pain behavioral tests, sixteen C57BL/6J mice were randomly divided into control and model groups, with 8 mice in each group, and a Von Frey filament was used to stimulate the referred somatic reactive regions in colitis mice, and the number of avoidance and paw withdraw reaction within 10 tests was recorded. For in vivo DRG calcium imaging tests, 24 Pirt-GCaMP6s transgenic mice were randomly and equally divided into control group and colitis model group. The responses of the neurons in L6 or L4 DRG to colorectal distension (CRD), lower back brushing, or mechanical stimulation at the hindpaw were observed using confocal fluorescence microscope. RESULTS: Compared with the control group, the area of EB exudation spot in the hindpaw and lower back regions was increased in the colitis model group (P<0.05), and the avoidance or paw withdraw numbers induced by Von Frey stimulation at the lower back and hindpaw were increased (P<0.01, P<0.05), indicating that colitis induced regional skin (acupoints) sensitization in the lower back and hindpaw regions. Compared with the control group, the percentage of L6 DRG neurons activated by 60 mm Hg CRD in the colitis model mice were apparently increased (P<0.01), the activated neurons mainly involved the medium-sized DRG neurons (P<0.01). In Pirt-GCaMP6s transgenic mice, following brushing the skin of the receptive field (lower back) of L6 DRG neurons, the fluorescence intensity of the brushing-activated DRG neurons and small, medium and large-sized neurons were significantly higher in the colitis model group than those in the control group (P<0.001, P<0.01, P<0.05). After brushing and clamping the skin of the right hindpaw (receptive field of L4 DRG neurons), the percentages of the activated L4 DRG neurons were obviously higher in the colitis model group than those in the control group (P<0.01, P<0.05), while there were no significant changes in the proportion of small, medium and large-sized neurons between the control and colitis model groups. CONCLUSIONS: Colitis may lead to body surface sensitization at the same and adjacent neuro-segments as well as to an increase of the number and activity of the responsive lumbar DRG neurons, among which the L6 DRG neurons at the same neuro-segment as the rectum colon showed an increase in the number of responders and intensity of calcium fluorescence signal while L4 DRG neurons at the level adjacent to the rectum colon showed an increase in the number of responders, suggesting that there may be different mechanisms of peripheral neural sensitization.

[Relationship between acupoint sensitization and changes in dorsal root ganglion neuron excitability in myocardial ischemia mice].

OBJECTIVE: To investigate the relationship between the sensitization state of acupoints on the surface of the myocardial ischemia (MI) model mice and the changes in the electrophysiological properties of the dorsal root ganglion (DRG) neurons in the corresponding spinal cord segment, and its underlying mechanism. METHODS: Sixty-eight male C57BL/6J mice were randomly divided into control and model groups (34 mice in each group). The model group received an intraperitoneal injection of 160 mg/kg isoproterenol (ISO) to establish the MI model, and the control group received an injection of the same dose of normal saline as the model group. After modeling for about 6 days, MI proportion was measured by HE staining to verify the pathological changes in the heart tissue. Evans blue (EB) dye was injected into the tail vein of mice to reflect the size, location, distribution, and number of exudates on the body surface. Then, whole-cell membrane currents, intrinsic excitability and membrane properties of different types of DRG neurons were evaluated by electrophysiological experiment in vitro. RESULTS: Compared with the control group, the heart size was larger, with pathological outcomes showing enlarged myocardial hypertrophy, destroyed structure of cardiomyocytes, with mononuclear cell infiltration among the cardiomyocytes in the model group. Compared with the control group, the number of EB exudation points was significantly increased (P<0.01), which were mainly concentrated in the epidermis near the T1-T5 segment of the spinal cord, "Feishu" (BL13), "Jueyinshu" (BL14) and "Xinshu" (BL15) in the model group. Compared with the control group, the rheobase and action potential amplitude (APA) of DRG medium-sized neurons were obviously decreased (P<0.01, P<0.05), while the whole-cell membrane currents, the spike numbers, the average instantaneous frequency, and the average discharge frequency were markedly increased (P<0.01). There were no significant alterations in the membrane properties and intrinsic excitability induced by depolarized currents of small-sized neurons between groups. Compared with the control group, the whole-cell membrane currents, spike numbers, and the average instantaneous frequency were significantly increased in the model group(P<0.05, P<0.01) while rheobase was significantly decreased (P<0.05) in DRG medium-sized neurons labeled with biotin and CGRP. CONCLUSION: After the mice were modeled by ISO, the DRG medium-size neurons in the T1-T5 segment of the spinal cord may mediate the sensitization of acupoints on the body surface through their different neuronal membrane properties and intrinsic excitabilities.

[Study on the correlation between the thickness of superficial fascia at Dazhui(GV14) and cervical spondylosis].

OBJECTIVE: To observe the correlation between the thickness of superficial fascia at Dazhui (GV14) acupoint and cervical spondylosis, so as to explore the essence of its morphological and structural changes of acupoint sensitivity. METHODS: A retrospective study was conducted. According to the diagnostic criteria of "Guidelines for Diagnosis, Treatment and Rehabilitation of Cervical Spondylosis" (2017), 344 cases of cervical spine magnetic resonance imaging (MRI) examination were included and divided into control group (73 cases) and observation group (271 cases). The control group was healthy population, and the observation group was patients with cervical spondylosis conforming to the diagnostic criteria, including cervical spondylosis of neck type, cervical spondylosis radiculopathy, cervical spondylotic myelopathy, cervical spondylosis of vertebral artery type, and sympathetic cervical spondylosis. According to MRI images of cervical spine, the structure of GV14 acupoint including skin, superficial fascia layer and aponeurosis ligament layer were measured. RESULTS: The acupoint depth and the superficial fascia thickness at GV14 in the observation group were (56.6±8.8) mm and (22.8±7.6) mm, the acupoint depth and the superficial fascia thickness at GV14 were (49.8±7.0) mm and (16.6±6.6)mm in the control group, which were significantly greater in the observation group than in the control group (P<0.01). The superficial fascia thickness at GV14 of cervical spondylotic mye-lopathy, cervical spondylosis of neck type and cervical spondylosis radiculopathy in the observation group was (23.8±8.1)mm, (23.0±7.3)mm and (22.6±6.5)mm, the acupoint depth of GV14 was (58.7±8.8)mm, (56.2±9.1)mm and (55.8±6.4)mm, which were significantly thicker than the superficial fascia thickness and the acupoint depth in the control group (P<0.01). In the observation group，the superficial fascia thickness of GV14 of cervical spondylosis myelopathy was significantly thicker than those of sympathetic cervical spondylosis (17.8±8.1) mm and cervical spondylosis of vertebral artery type (19.9±5.9) mm (P<0.01, P<0.05). In the observation group, the depth of GV14 of cervical spondylosis myelopathy was thicker than that of cervical spondylosis of neck type, cervical spondylosis radiculopathy, sympathetic cervical spondylosis and cervical spondylosis of vertebral artery type(P<0.05，P<0.01)； the depth of GV14 of sympathetic cervical spondylosis was thinner than that of cervical spondylosis of neck type and cervical spondylosis radiculopathy (P<0.01). CONCLUSION: The superficial fascia thickness at GV14 was correlated with cervical spondylosis, and it is also related to cervical spondylotic myelopathy, cervical spondylosis of neck type and cervical spondylosis radiculopathy. The morphological and structural changes of GV14 in the state of cervical spondylosis were mainly the thickness of the superficial fascia.

[Research on mechanisms of acupoint sensitization in gastric ulcer mice from perspective of dorsal root ganglion neuronal excitability].

OBJECTIVE: To investigate the relationship between acupoint sensitization on the body surface and neuronal intrinsic excitability of the medium- and small-size dorsal root ganglion (DRG) neurons from the perspective of ion channel kinetics in mice with gastric ulcer. METHODS: Male C57BL/6J mice were randomly divided into control (n=32) and model groups (n=34). The gastric ulcer model was established by injection of 60% glacial acetic acid (0.2 mL/100 g) into the gastric wall muscle layer and submucosa near the pylorus in the minor curvature of the stomach. In contrast, the same dose of normal saline was injected in the same way in the control group. Six days after modeling, Evans blue (EB) solution was injected into the mouse's tail vein for observing the number and distribution of the exudation blue spots on the body surface. Histopathological changes of the gastric tissue were observed by H.E. staining. Then, whole-cell membrane currents and intrinsic excitability of medium- and small-size neurons in the spinal T9-T11 DRGs were measured by in vitro electrophysiology combining with biocytin-ABC method. RESULTS: In the control group, EB exudation blue spots were not obvious, while in the model group, the blue spots on the body surface were densely distributed in the area of spinal T9-T11 segments, the epigastric region, and the skin around "Zhongwan" (CV12) and "Huaroumen" (ST24) regions, and near the surgical incision region. Compared with the control group, the model group had a high level of eosinophilic infiltrates in the submucosa of gastric tissues, severe gastric fossa structure damage, gastric fundus gland dilation and other pathological manifestations. The number of exudation blue spots was proportional to the degree of inflammatory reaction in the stomach. In comparison with the control group, the spike discharges of type II of medium-size DRG neurons in T9-T11 segments were decreased, and the current of whole-cell membrane was increased, basic intensity was decreased (P<0.05), discharge frequency and discharge number were increased (P<0.01,P<0.000 1); while the discharges of type I small-size DRG neurons were decreased, those of type II neurons increased, the whole-cell membrane current was decreased, and discharge frequency and discharge number were decreased (P<0.01, P<0.000 1). CONCLUSION: Both the medium- and small-size DRG neurons from the spinal T9-T11 segments involve in gastric ulcer-induced acupoint sensitization via their different spike discharge activities. And intrinsic excitability of these DRG neurons can not only dynamically encode the plasticity of acupoint sensitization, but also can help us understand the neural mechanism of acupoint sensitization induced by visceral injury.

Study on the Specific Expression of Infrared Radiation Temperature on the Body Surface of Acupoint in Rats with Chronic Myocardial Ischemic Injury.

BACKGROUND: Infrared thermal imaging technology was used to observe the changes in infrared radiation temperature at acupoints in rats caused by chronic myocardial ischemia injury. OBJECTIVE: This study aims to compare the difference of body surface infrared radiation temperature information of three groups of acupoints: bilateral Neiguan (PC6), bilateral Yanglingquan (GB33), and bilateral Sham Acupoints (SA) in the pathological state of myocardial ischemia injury, and to explore the relationship between acupoints and viscera state. METHODS: SPF adult Wistar male rats (n = 20) were randomly divided into a control (CTL; n = 10) and an isoproterenol group (ISO; n = 10). Chronic myocardial injury was induced in rats by subcutaneous injection of isoproterenol hydrochloride for 14 d. On the second day after the establishment of the model, the serum levels of cardiac troponin (cTnI) and creatine kinase isoenzyme (CK-MB) were measured by enzyme-linked immunosorbent assay (ELISA). The morphological changes of the myocardial tissue in the two groups were observed by hematoxylin-eosin (HE) staining and their pathological scores were evaluated, which was then used to determine the myocardial ischemic injury. Two days before and after the establishment of the model, the electrocardiograms (ECG) of the two groups of rats were recorded by the (ECG) data acquisition system, and the infrared thermal imaging platform was used to detect the temperature of the six acupoints. RESULTS: 1. After subcutaneous injection of isoproterenol hydrochloride for 14 days, the ST segment of the ECG decreased in the ISO group compared with that of the CTL group; 2. Myocardial tissue injury was serious in the ISO group compared to the CTL group; 3. Serum cTn-I and CK-MB were significantly increased (P <0 01) in the ISO group, compared to that in the CTL group; 4. The infrared radiation temperature on the body surface of bilateral Neiguan (PC6) acupoints decreased significantly in the ISO group, compared to that of the CTL group. CONCLUSION: Infrared thermal imaging technology can be used to detect the changes in the energy state of acupoints. Chronic myocardial ischemic injury can cause a decrease in IR temperature on the body surface of bilateral Neiguan (PC6) acupoints, suggesting that visceral diseases can lead to changes in the energy metabolism of acupoints.

An infrared thermographic analysis of the sensitization acupoints of women with primary dysmenorrhea.

OBJECTIVE: To explore the sensitization acupoints of women with primary dysmenorrhea (PD) by comparing infrared radiation temperatures between acupoints and non-acupoints. METHODS: We tested 10 acupoints of every woman with PD and healthy subjects on premenstrual, menstrual, and postmenstrual days using an infrared imaging device. The primary outcome was the absolute value of body surface temperature difference (AVTD) between the left and right sides of the same testing point. RESULTS: A total of 58 PD patients and 57 healthy volunteers completed the test from May 2016 to May 2017. Compared with the healthy group, we observed a significant reduction and increase in the AVTD in Taichong (LR3) and Sanyinjiao (SP6), respectively, during menstrual days in the PD group (= 0.01; = 0.04); while during postmenstrual days, all AVTDs of Shuiquan (KI5), Diji (SP8), and Xuehai (SP10) were diminished in the PD group (= 0.01; = 0.03; = 0.01, respectively). No significant differences in AVTD were detected at any other points or testing times. CONCLUSIONS: Compared with the healthy group, the AVTDs of Taichong (LR3), Sanyinjiao (SP6), Shuiquan (KI5), Diji (SP8), and Xuehai (SP10) at menstruation-relevant points of PD patients were sensitized, providing a reference for the selection of acupoints in the treatment of PD.

[Sensory and sympathetic nerves are involved in the changes of skin temperature, blood infusion and inflammatory cytokines of cutaneous tissue in the sensitized area of colitis rats].

OBJECTIVE: To investigate the changes of skin temperature, blood infusion and inflammatory cytokines of cutaneous tissue in the sensitized area of colitis model rats, as well as the relationship between sensory and sympathetic nerves and the formation of sensitized area, and to initially reveal the partial physical-chemical characteristics of the sensitized area in the colitis model rats. METHODS: Thirty-five male SD rats were randomly divided into a control group (n=10), a model group (n=18) and a guanethidine group (n=7). 5% dextran sulfate sodium (DSS) was adopted for 6-day free drinking to establish colitis model in the model group and the guanethidine group. On day 6 and 7, in the guanethidine group, guanethidine solution (30 mg/kg) was injected intraperitoneally for sympathetic block. On day 7, after injection of evans blue (EB) solution, the EB extravasation areas on the body surface were observed to investigate the distribution and physical-chemical characteristics of the sensitized area. The control area was set up, 0.5 cm away from the sensitized area, and with the same nerve segment innervation. Disease activity index (DAI) score of rats was compared between the normal group and the model group, and the morphological changes in the colon tissue were investigated with HE method. Using infrared thermal imaging technology and laser speckle flow imaging technology, skin temperature and blood infusion were determined in the sensitized area and the control area of the rats in the model group. Immunofluorescence technique was adopted to observe the expression levels of the positive nerve fibers of substance P (SP), calcitonin gene-related peptide (CGRP) and tyrosine hydroxylase (TH), and the correlation with blood vessels; as well as the expression levels of SP positive nerve fibers/tryptase+ mast cells, and tryptase+ mast cells/5-hydroxytryptamine (5-HT) in skin tissue in the sensitized area and the control area of the rats in the model group. MSD multi-level factorial method and ELISA were applied to determine the contents of pro-inflammatory and anti-inflammatory cytokines (e.g. TNF-α, IL-1ß, IL-6, IL-4 and IL-10) and anti-inflammatory substance corticosterone (CORT). RESULTS: Sensitization occurred at the T12-S1 segments of the colitis model rats, especially at L2-L5 segments. Compared with the normal group, DAI score was increased in the rats of the model group (P<0.05), and the colonic mucosal damage was obvious, with the epithelial cells disordered, even disappeared, crypt destructed, submucosal edema and a large number of inflammatory cells infiltrated. In comparison with the control area, the skin temperature and blood infusion were increased in the sensitized area of the model group (P<0.05, P<0.01); as well as the expression levels of the positive nerve fibers of SP, CGRP and TH of skin tissue (P<0.05), which was specially distributed in peripheral vessels, the expression levels of SP positive nerve fibers/tryptase+ mast cells, and tryptase+ mast cells/5-HT of the skin tissue were all expanded (P<0.05) in the sensitized area of the model group. Compared with the model group, the number of sensitized areas was reduced in the guanethidine group (P<0.05). In comparison with the control area of the model group, in the sensitized area, the contents of pro-inflammatory cytokines, e.g. TNF-α, IL-1ß and IL-6, and the anti-inflammatory substance CORT of skin tissue were all increased (P<0.05); and the contents of IL-6 and TNF-α were negatively correlated with CORT (P<0.05). CONCLUSION: The sensitized areas on the body surface of colitis rats are mainly distributed in the L2-L5 segments. Sensory and sympathetic nerves are involved in the acupoint sensitization, and the sensitized areas may have the dynamic changes in pro-inflammatory and anti-inflammatory substances.

[Discussion of novel mode of acupuncture and moxibustion based on identifying the acupoint sensitization].

On the base of the paradigms of clinical studies on modern moxibustion by identifying the acupoint sensitization, the records of ancient literature in successive dynasties were collected on "identifying the sensitization" of acupoints in acupuncture. In association with acupoint detection of acupuncture recorded in current textbooks, a novel concept, "exerting acupuncture by identifying the acupoint sensitization" is proposed. Acupoint sensitization is the common initial link of effect achieved by both acupuncture and moxibustion. Hence, on the basis of the routine acupoint selection by differentiating syndrome, the state of acupoint must be considerably emphasized in either acupuncture or moxibustion. The clinical curative effect may be improved by selecting the sensitized points and identifying sensitization. This novel mode of diagnosis and treatment focuses on identifying acupoint sensitization by unifying acupuncture with moxibustion and in coincidence with the modern clinical characteristics of either acupuncture or moxibustion.

[Effect of electroacupuncture on mood and estrogen receptor α expression in mice with polycystic ovary syndrome induced by bisphenol A exposure].

OBJECTIVE: To compare the effect of electroacupuncture (EA) on "Guanyuan" (CV4) or sensitization points in mice with polycystic ovary syndrome (PCOS), so as to explore its mechanisms underlying improvement of PCOS. METHODS: In the first part of this study, 26 female ICR mice were randomized into control group (8 mice) and model group (18 mice). The PCOS model was established by gavage of bisphenol A (BPA) at a dose of 100 mg/kg, and the control group were gavage of equal volume of corn oil, once daily, 5 days a week for 4 conse-cutive weeks. Evans blue (EB) dye (0.1 mL/10 g) was injected into the caudal vein after modeling. The size, number and distribution of EB exudation points at the skin were observed. In the second part of this study, 32 mice were randomized into control, model, EA-CV4 and EA-sensitization points groups (8 mice in each group). EA (2 Hz, 2 mA) was applied to the sensitization points or CV4 for 20 min, once daily, 5 days a week for 4 conse-cutive weeks. The body weight was measured once a week for 8 consecutive weeks. The behavior changes were evaluated by open field test and elevated plus maze test. H.E. staining was used to observe the histopathologic changes of the ovary tissue. Serum level of estradiol (E2) was measured by ELISA. The expressions of estrogen receptor α (ER-α) in ovarian and uterine tissues were detected by Western blot and immunofluorescence. RESULTS: (1) In PCOS mice, the EB exudation points were found to overlap the lower abdomen, lumbosacral, chest, back and lower limbs regions, and the number of EB points was significantly more than that of the control group (P<0.01). (2) After the intervention and compared with the control group, the ovaries showed polycystic changes and an increase of atresia follicles with a larger diameter, the activity time in the central area, the total distance of movement, the times of open-arm entries, the duration in open-arm, the serum E2 content and the expression of ER-α in ovarian tissue were significantly decreased (P<0.01, P<0.05), while the mice's body weight and the expression of ER-α in uterine tissue were increased (P<0.05) in the model group. After the intervention and compared with the model group, a small number of normal follicles and corpus luteum were observed under microscope, the activity time in the central area, the total distance of movement, the times of open-arm entries, the duration in open-arm, the serum E2 content and the expression of ER-α in ovarian tissue were significantly increased (P<0.05, P<0.01), while the mice's body weight and the expression of ER-α in uterine tissue was decreased (P<0.05) in both EA-CV4 and EA-sensitization points groups. CONCLUSION: EA at sensitization points and CV4 can regulate the expression of estrogen and ER-α in PCOS mice, and improve the anxiety like behavior. EB exudation points on the body surface can not only reflect the functional changes of organs, but also treat diseases through body surface stimulation, suggesting a dual role in diagnosis and treatment.

Skin Temperature of Acupoints in Health and Disease: A Systematic Review.

Introduction: Despite substantial progress made in the field of acupuncture research, the existence and specificity of acupoints remain controversial. In recent years, the concept of acupoint sensitization has emerged as a theoretical framework for understanding acupoints as dynamic functional entities that are sensitized in pathological conditions. Based on this premise, some have claimed that specific acupoints are thermally distinct between healthy and clinical populations, but no systematic review has been conducted to synthesize and evaluate the quality of studies supporting such claims. In this review, we provide a summary and quality assessment of the existing literature addressing the question of whether changes in skin temperature at specific acupoints are indicative of pathological conditions. Methods: A systematic literature search was performed in PubMed, EMBASE, and AltHealthWatch (EBSCO Host), by combining variations of search terms relevant to acupoints and temperature. The search was limited to the English language, and publication dates ranged from database inception to December 2020. Two authors independently screened all resulting abstracts and subsequently read full-text articles for eligibility. Information on study design, sample, acupoints, parameters of skin temperature assessments, and main findings were extracted from included studies. Quality of the thermal sensing methodology was evaluated using a thermal assessment checklist, adapted from the Thermographic Imaging in Sports and Exercise Medicine (TISEM) consensus checklist, and a modified Newcastle-Ottawa Scale (NOS) for case-control studies. Results: The search strategy yielded a total of 1771 studies, of which 10 articles met the eligibility criteria. Eight studies compared skin temperature at acupoints in healthy versus clinical populations, and two studies assessed within-subject changes in temperature of acupoints in relation to changes in health status. There were seven clinical conditions examined in the included studies: chronic bronchial asthma, chronic hepatitis, hyperplasia of mammary glands, infertility, intracranial hypertension, obesity, and primary dysmenorrhea. There were numerous methodological quality issues related to skin temperature measurements. Eight studies with case-control designs reported significant differences between healthy and clinical populations in temperature at certain acupoints. Two studies with pre-post designs reported that changes in health-disease status could be associated with changes in temperature at specific acupoints. Conclusion: A review of the available literature suggests that certain acupoints may be thermally distinct between healthy and unhealthy states. However, given the methodological limitations and heterogeneity across included studies, no definitive conclusion could be drawn as to whether changes in skin temperature at specific acupoints are indicative of pathological conditions.

Mast Cells and Acupuncture Analgesia.

Mast cells are widely distributed in various parts of the human body and play a vital role in the progression of many diseases. Recently, the close relationship between mast cells and acupoints was elucidated, and the role of mast cells in acupuncture analgesia has attracted the attention of researchers worldwide. Using mast cells, acupuncture analgesia and acupoint as key words to search CNKI, PubMed, Web of Science and other databases, combining the representative articles in these databases with the published research papers of our group, we summarized: The enrichment of mast cells and the dense arrangement of collagen fibers, microvessels, and nerves form the basis for acupoints as the reaction sites of acupuncture; acupuncture can cause the deformation of collagen fibers and activate TRPV channels on mast cells membrane, so as to stimulate mast cells to release bioactive substances and activate nerve receptors to generate analgesic effect; system biology models are set up to explain the quantitative process of information initiation and transmission at acupuncture points, and indicate that the acupuncture effect depends on the local mast cells density. In a conclusion, this review will give a scientific explanation of acupuncture analgesia from the material basis of acupoints, the local initiation, and afferent biological mechanism.

[Revealing characteristics and rules of acupoint sensitization phenomena: based on knee osteoarthritis].

OBJECTIVE: To explore the characteristics and rules of acupoint sensitization phenomena based on knee osteoarthritis (KOA), one of the clinical dominant diseases of acupuncture-moxibustion. METHODS: In combination with literature and expert experiences, the acupoints with the highest use frequency in treatment of KOA were screened, e.g. Heding (EX-LE 2), Liangqiu (ST 34), Mingmen (GV 4), Neixiyan (EX-LE 4), Ququan (LR 8) and Dubi (ST 35). In 814 patients with KOA and 217 healthy subjects, the acupoint temperature, mechanic pain threshold and pressure pain threshold were detected separately. Using machine learning method, the sensitization was judged at each acupoint. RESULTS: Compared with healthy subjects, the acupoint temperature was increased and the mechanic pain threshold and pressure pain threshold were reduced in KOA patients (P<0.05). Besides, the cut-off value was presented to distinguish whether the acupoint was sensitized or not. The results of machine learning showed that the highest prediction accuracy of acupoint sensitization was 86.7% (Shenshu [BL 23]) and the lowest one was 73.9% (Heding [EX LE 2]). The prediction accuracy at the third clinical stage trial was higher, the highest was 93.3% (Ququan [LR 8]) in KOA patients. CONCLUSION: It is confirmed that the acupoint sensitization reflects the characteristics of disease and is correlative with the conditions of illness, which may provide the reference for the auxiliary diagnosis and condition assessment of KOA.

Discussion of novel mode of acupuncture and moxibustion based on identifying the acupoint sensitization / 中国针灸

On the base of the paradigms of clinical studies on modern moxibustion by identifying the acupoint sensitization, the records of ancient literature in successive dynasties were collected on "identifying the sensitization" of acupoints in acupuncture. In association with acupoint detection of acupuncture recorded in current textbooks, a novel concept, "exerting acupuncture by identifying the acupoint sensitization" is proposed. Acupoint sensitization is the common initial link of effect achieved by both acupuncture and moxibustion. Hence, on the basis of the routine acupoint selection by differentiating syndrome, the state of acupoint must be considerably emphasized in either acupuncture or moxibustion. The clinical curative effect may be improved by selecting the sensitized points and identifying sensitization. This novel mode of diagnosis and treatment focuses on identifying acupoint sensitization by unifying acupuncture with moxibustion and in coincidence with the modern clinical characteristics of either acupuncture or moxibustion.

Revealing characteristics and rules of acupoint sensitization phenomena: based on knee osteoarthritis / 中国针灸

OBJECTIVE@#To explore the characteristics and rules of acupoint sensitization phenomena based on knee osteoarthritis (KOA), one of the clinical dominant diseases of acupuncture-moxibustion.@*METHODS@#In combination with literature and expert experiences, the acupoints with the highest use frequency in treatment of KOA were screened, e.g. Heding (EX-LE 2), Liangqiu (ST 34), Mingmen (GV 4), Neixiyan (EX-LE 4), Ququan (LR 8) and Dubi (ST 35). In 814 patients with KOA and 217 healthy subjects, the acupoint temperature, mechanic pain threshold and pressure pain threshold were detected separately. Using machine learning method, the sensitization was judged at each acupoint.@*RESULTS@#Compared with healthy subjects, the acupoint temperature was increased and the mechanic pain threshold and pressure pain threshold were reduced in KOA patients (P<0.05). Besides, the cut-off value was presented to distinguish whether the acupoint was sensitized or not. The results of machine learning showed that the highest prediction accuracy of acupoint sensitization was 86.7% (Shenshu [BL 23]) and the lowest one was 73.9% (Heding [EX LE 2]). The prediction accuracy at the third clinical stage trial was higher, the highest was 93.3% (Ququan [LR 8]) in KOA patients.@*CONCLUSION@#It is confirmed that the acupoint sensitization reflects the characteristics of disease and is correlative with the conditions of illness, which may provide the reference for the auxiliary diagnosis and condition assessment of KOA.

[Roles of nociceptors in acupoint sensitization: recent advances].

Hyperalgesia and functional plasticity are the important components of acupoint sensitization. Reveal of the neuromechanism of acupoint sensitization may play a positive role in promoting the development of acupuncturology in the world. The nociceptors, including Aδ and C subtypes distributing in the acupoint region and target organs, are responsible for the transmission of signals of peripheral noxious stimuli and acupuncture-liking stimulation to the dorsal horns of the spinal cord and supraspinal levels. A previous study reveals that the C type nociceptors are involved in the acupoint sensitization. Recent studies indicate that there exists a subtype of mechanical responsiveness in the C type receptors, named "silent nociceptor" which is awa-kened when diseases occur, being very similar to the dynamic sensitization characteristics of acupoints. Hence, we, in the present review, make a discussion about the role of C-type silent nociceptor in the hyperalgesia and functional plasticity of the sensitized acupoint according to previous studies and recent advances, so as to provide more ideas and opportunities for the investigation on the scientific characteristics of acupoints.

[On the acupoint and its specificity].

Although acupuncture has spanned thousands of years in the history of traditional medicine, still some basic questions are not clarified. Acupuncture is the theory based on long time medical practice of the ancient sage, combined with objectivesymptom and medical expertise from diseases, and being applied for the instruction in clinic. In this way, acupoint is discovered by doctors in the practice of disease treatment other than a natural occurrence in the healthy population. And acupoint specificity is attached to the target organ involved in pathological condition. In our opinion, acupoint originates from somatic referred area reactive to visceral disorders. And accordingly, referred hyperesthesia of the somatic area is phenomenon of acupoint sensitization. Acupoint is the situ having health code formed in the biological evolution. Corresponding acupoint of a given organ is the alarmer for the state of health, and also is the trigger for self-healing where acupuncture can work as a gating-button. Therefore, acupoint must be accompanied with diseases in that it is reinforced by, relayed on, responsive to and neutralize by the pathological course. In conclusion, acupoint cannot exist without the disease. In another word, acupoint will be unshown, or be functionally hidden, under physiological condition.

[Association between skin microecology and acupoint sensitization].

The skin microecology interacts with the immune system for a lifetime, and the skin microecology is in dynamic balance in the physiological state. The flora with the same physical and chemical properties on the surface of the skin can maintain a relatively stable state in a certain period of time, and there are dynamic changes of microflora in both physiology and disease state. Combined with the study of the relationship among skin microorganisms, skin diseases and visceral diseases, the relationship between skin microecological changes and visceral pathological state is explored. On this basis, it is proposed that the sensitized acupoint is an abnormal manifestation of the body homeostasis imbalance on the body surface, and the local substance variation on the sensitization acupoint may induce microbial changes. In terms of treatment, moxibustion and other surface treatments that function through immunity may also involve microorganisms.

[Photoacoustic imaging study on spatial structure of microvessels around acupoints in mice with acute myocardial ischemia].

OBJECTIVE: To observe the changes of microvascular structure of acupoints caused by myocardial ischemia, so as to explore the application of photoacoustic imaging technology in the research of acupoint sensitization. METHODS: Twelve BALB/c mice were randomly divided into normal, sham operation and acute myocardial ischemia (AMI) model groups, with 4 mice in each group. AMI model was established by ligating the left anterior descending coronary artery. Electrocardiogram (ECG) was recorded by physiological signal acquisition system at 12 h and on the 14th day after modeling, and serum cardiac troponin T (cTnT) and creatine kinase isoenzyme MB (CK-MB) levels were detected by enzyme-linked immunosorbent assay. The microvascular structure changes of acupoints "Feishu"(BL13), "Jueyinshu"(BL14), "Quze"(PC3) and "Chize"(LU5) were observed by photoacoustic imaging technology, and distance (DM), inflection count metric (ICM), sum of angle metric(SOAM)and microvessel density (MVD) were calculated by microvascular quantification algorithm. RESULTS: Compared with the normal and sham operation groups, the ST segment of ECG was obviously elevated, serum cTnT and CK-MB were significantly increased in AMI model group at 12 h and on the 14th day after AMI (P<0.01). The ICM of BL14 in AMI model group was significantly decreased on the 14th day than that on the 7th day after AMI. Compared with the normal group, the ICM of BL14 was significantly increased in AMI model group on the 7th day after AMI(P<0.05). There were no significant changes in DM, ICM, SOAM and MVD at other acupoints on the 7th and 14th day (P>0.05) among the three groups. CONCLUSION: The change of ICM may be one of the characteristics of acupoint sensitization and photoacoustic imaging technology can be used to study the structure of acupoint microvessels.

[Acupoint sensitization enhances inhibitory effect of electroacupuncture on jejunum mobility in rats].

OBJECTIVE: To observe the effect difference of electroacupuncture (EA) at the sensitized and non-sensitized acupoint "Tianshu" (ST25) on the motility of jejunum in rats. METHODS: Male SD rats were randomly divided into blank control, sensitized ST25 (sensitization), and non-sensitized ST25 (non-sensitization) groups (n=16 in each group). The sensitization and non-sensitization were induced by injection of 15% mustard oil (20 µL) and Paraffin oil (20 µL) into the left ST25 area respectively. The rats' behavior reactions were assessed by recording the numbers and duration of licking the local sensitized skin region. At the end of experiments and after regular trans-cardiac perfusion and fixing with 10% neutral formaldehyde, the skin and muscular tissues of the ST25 region (1 cm×1 cm) were taken for H.E. staining to observe the local histopathologic changes. The intestinal motility was detected by recording the contraction pressure waves of jejunum through a small balloon-connected pressure transducer and an amplifier, followed by calculating the ratios of amplitude and frequency of contraction waves between pre- and post-EA stimulation. EA (2 Hz, 0.2-6.0 mA) was applied to the sensitized and non-sensitized ST25 regions for 20 s for comparing their effects on jejunum motility. RESULTS: Compared with the blank control group, mustard oil injection but not Paraffin oil injection resulted in histological edema and neutrophils infiltration in tissues of ST25 region, and also striking increase of the number and duration of licking (P<0.01), suggesting a sensitization of ST25 area after mustard oil injection. The ratios of spontaneous contraction amplitude and frequency of jejunum were remarkably decreased in mustard oil-treated rats compared to baseline and Paraffin oil group (P<0.001，P<0.01). The maximum inhibitory effect of EA on the intestinal movement amplitude was significantly higher in the sensitization group than in the blank control and non-sensitization groups (P<0.05，P<0.01), and there was a dose-effect relationship between the current intensity of EA (0.5-3.0 mA) and the inhibitory rate 50% of the contraction amplitude (not the frequency) in the sensitization group (P<0.001), but not in the blank control and non-sensitization groups (P>0.05). Additionally, 1.5 mA EA stimulation at the sensitized ST25 (not at the non-sensitized ST25) had an inhibitory effect on the contraction amplitude (P<0.05) rather than on the contraction frequency (P>0.05) in comparison with the blank control group. CONCLUSION: Sensitization of acupoint ST25 can modulate the motility of jejunum and enhances the inhibitory effect of EA on the contraction amplitude of jejunum in rats. The inhibitory effect of sensitized ST25 EA is evidently stronger than that of the non-sensitized ST25 EA.