OBJECTIVE: To observe the effects of acupuncture at \"antihypertensive acupoint prescription\" on endothelial active factors and related autonomic neurotransmitters in spontaneous hypertension rats, and explore the vascular regulation and central regulation mechanisms of acupuncture for anti-hypertension.
METHODS: Thirty SPF grade male spontaneous hypertension rats were randomly divided into a model group (15 rats) and an acupuncture group (15 rats). Besides, 15 Wistar Kyoto rats were collected as a blank control group (normal group). In the acupuncture group, acupuncture was delivered at the \"antihypertensive acupoint prescription\" (bilateral \"Renying\" [ST 9], \"Quchi\" [LI 11], \"Zusanli\" [ST 36], \"Taichong\" [LR 3] and \"Neiguan\" [PC 6]), with needles retained for 30 min, once daily. The duration of intervention was 28 days. Every week, using the the irritation scale, the sign of sympathetic irritation was evaluated dynamically. The arterial blood pressure of the rats tail was determined, using non-invasive blood pressure measurement system. ELISA was adopted to detect the levels of calcitonin gene-related peptide (CGRP), nitric oxide (NO), endothelin-1 (ET-1), neuropeptide Y (NPY) in the serum. DAB chromogenic in situ hybridization (CISH) was provided to detect the mRNA expression of endothelial nitric oxide synthase (eNOS) in the internal carotid artery and the arcuate nucleus (ARC), and that of CGRP in the paraventricular nucleus posterior (PVP) and the ventrolateral medulla (VLM). Liquid chromatography-mass spectrometry (LC-MS) was used to detect the levels of epinephrine (E) and norepinephrine (NE) in the paraventricular nucleus anterior (PVA).
RESULTS: Compared with the normal group, the irritation scores, systolic blood pressure and diastolic blood pressure were increased at each time point in the model group (P<0.05). When compared with the model group, the irritation scores after the intervention for 3 and 4 weeks, and systolic and diastolic blood pressure after intervention for 2, 3 and 4 weeks were reduced in the acupuncture group (P<0.05). In comparison with the normal group, the serum CGRP and NO levels of the rats were decreased (P<0.05), and the serum ET-1 and NPY levels, as well as E and EN levels in PVA were increased (P<0.05) in the model group. The levels of serum CGRP and NO were elevated (P<0.05), and the serum ET-1 and NPY levels, as well as E and EN levels of PVA were reduced (P<0.05) in the acupuncture group when compared with those of the model group. In the model group, the media of internal carotid artery exhibited thickening and remodeling, while the neuron volume in ARC was small. In the acupuncture group, every layer of internal carotid artery was acceptably arranged, and the parvicellular neuron of ARC was moderate in volume. For the in situ hybridization of eNOS mRNA for the rats of each group, the smooth muscle cells were predominantly expressed in each layer of the internal carotid artery, whereas the expression of parvicellular neurons was dominated in ARC. In the model group, the large and small neurosecretory cells were distributed sparsely in the nerves of PVP; in the acupuncture group, the cells of these two species were distributed regularly; and there were few species of glial cell in the VLM of either the model group or the acupuncture group. In each group, for the in situ hybridization of CGRP mRNA, the small neurosecretory cells were expressed predominately in the PVP, while, the expression of glial cell nuclei and the cell cytoplasm was dominated in the VLM. Compared with the normal group, the mRNA expression of eNOS in the internal carotid artery and ARC and that of CGRP mRNA in the PVP and VLM was decreased in the model group (P<0.05). In the acupuncture group, when compared with the model group, the mRNA expression of eNOS in the internal carotid artery and ARC and that of CGRP in the PVP and VLM was increased in the acupuncture group (P<0.05).
CONCLUSIONS: Acupuncture at \"antihypertensive acupoint prescription\" can upregulate the level of vascular relaxing factors, downregulate the level of contracting factors, enhance the response of relaxing factors in targeting blood vessels and regulating the center. The mechanism may be related to the modulation of the sympathetic-adrenergic autonomic neurotransmitters in the paraventricular nucleus in spontaneous hypertension rats.
目的：观察针刺“降压方”对自发性高血压大鼠（SHR）内皮活性因子及相关自主神经递质的影响，探讨针刺降压的血管调节和中枢调控机制。方法：将30只SPF级雄性SHR随机分为模型组（15只）、针刺组（15只），另以15只京都种Wistar大鼠（WKR）为空白对照组（正常组）。针刺组予“降压方”（双侧“人迎”“曲池”“足三里”“太冲”“内关”）针刺，留针30 min，每日1次，共干预28 d。每周采用激惹评分动态评价大鼠交感激惹表征；通过全自动无创血压测量系统检测大鼠尾动脉血压；ELISA法检测血清降钙素基因相关肽（CGRP）、一氧化氮（NO）、内皮素-1（ET-1）、神经肽Y（NPY）含量；DAB显色原位杂交（CISH）检测颈内动脉、弓状核内皮型一氧化氮合酶（eNOS）及室旁核后部、延髓腹外侧CGRP mRNA表达；液相色谱及质谱联用检测室旁核前部肾上腺素（E）、去甲肾上腺素（NE）含量。结果：与正常组比较，模型组大鼠观察期间各时间点激惹评分及收缩压、舒张压升高（P<0.05）；与模型组比较，针刺组大鼠干预第3、4周后激惹评分及干预第2、3、4周后收缩压、舒张压降低（P<0.05）。与正常组比较，模型组大鼠血清CGRP、NO含量降低（P<0.05），血清ET-1、NPY含量及室旁核前部E、NE含量升高（P<0.05）；与模型组比较，针刺组大鼠血清CGRP、NO含量升高（P<0.05），血清ET-1、NPY含量及室旁核前部E、NE含量降低（P<0.05）。模型组大鼠颈内动脉中膜增厚且有重构表现，弓状核神经元体积较小；针刺组大鼠颈内动脉各层排布尚可，弓状核小细胞神经元适中。各组大鼠eNOS mRNA在颈内动脉主要表达于各层中平滑肌细胞，而在弓状核主要表达于小细胞神经元。模型组大鼠室旁核后部神经分泌大细胞及小细胞分布较为稀疏，针刺组大鼠两类细胞排布尚可；模型组、针刺组大鼠延髓腹外侧区胶质细胞种类相对较少。各组大鼠CGRP mRNA在室旁核后部主要表达于神经分泌小细胞，而在延髓腹外侧主要表达于胶质细胞核及细胞质。与正常组比较，模型组大鼠颈内动脉及弓状核eNOS mRNA、室旁核后部及延髓腹外侧CGRP mRNA表达降低（P<0.05）；与模型组比较，针刺组大鼠颈内动脉及弓状核eNOS mRNA、室旁核后部及延髓腹外侧CGRP mRNA表达增加（P<0.05）。结论：针刺“降压方”可上调血管舒张因子水平，下调血管收缩因子水平，同时增强血管舒缩因子靶向血管及调控中枢的响应，其机制可能与调节SHR室旁核交感肾上腺素能自主神经递质有关。.

Neurotransmitters are key modulators in neuro-immune circuits and have been linked to tumor progression. Medullary thyroid cancer (MTC), an aggressive neuroendocrine tumor, expresses neurotransmitter calcitonin gene-related peptide (CGRP), is insensitive to chemo- and radiotherapies, and the effectiveness of immunotherapies remains unknown. Thus, a comprehensive analysis of the tumor microenvironment would facilitate effective therapies and provide evidence on CGRP\'s function outside the nervous system. Here, we compare the single-cell landscape of MTC and papillary thyroid cancer (PTC) and find that expression of CGRP in MTC is associated with dendritic cell (DC) abnormal development characterized by activation of cAMP related pathways and high levels of Kruppel Like Factor 2 (KLF2), correlated with an impaired activity of tumor infiltrating T cells. A CGRP receptor antagonist could offset CGRP detrimental impact on DC development in vitro. Our study provides insights of the MTC immunosuppressive microenvironment, and proposes CGRP receptor as a potential therapeutic target.

BACKGROUND: The leaves of Artemisia argyi Levl.et Vant. have a long history of being used to treat skin diseases such as pruritus and dermatitis in China, but the therapeutic effect on allergic contact dermatitis (ACD) is still unclear.
OBJECTIVE: To investigate the effect and molecular mechanisms of the volatile oil of A. argyi leaves (abbreviated as \'AO\') in the treatment of ACD.
METHODS: The main components in AO were analyzed using GC-MS. The effect of AO on channel currents in hTRPA1-transfected HEK293T cells was studied by whole-cell patch clamp. Subsequently, chloroquine-evoked acute itch and squaraine dibutyl ester (SADBE)-induced ACD chronic itch model was established to evaluate the antipruritic effect through counting scratching behavior, and the anti-inflammatory effects on ACD mice were measured using histological analysis. Meanwhile, the changes of CGRP, the infiltration of nerve fibers and the recruitment of dendritic cells, the expression of Il-23 and Il-17 mRNA in skin lesions, the phosphorylation of ERK and p38 in dorsal root ganglion (DRG), were evaluated by molecular biological methods. Then the inhibitory effect of AO on AITC- or SADBE-activated TRPA1 channels in primary DRG neurons of C57BL/6, Trpa1-/- or Trpv1-/- mice was elucidated by Ca2+ imaging and immunofluorescence.
RESULTS: AO treatment inhibited the activation of TRPA1 in HEK293T cells and alleviated acute itch caused by chloroquine, but this effect was lacking in Trpa1-/- mice. Furthermore, administration of AO attenuated scratching behavior in SADBE-induced ACD mice. AO also inhibited the increase of nerve fibers and recruitment of dendritic cells, and down-regulated the expression of CGRP and the levels of Il-23 and Il-17 mRNA. Meanwhile, AO reduced the expression of p-p38 and p-ERK in the lesioned skin and DRG of SADBE-induced ACD mice. Additionally, AO blocked the activation of TRPA1 channels and decreased the levels of CGRP, p-p38, and p-ERK in DRG neurons.
CONCLUSIONS: AO could inhibit TRPA1 channels in sensory neurons, thereby reducing the release of CGRP and exerting anti-pruritic and anti-inflammatory effect. These findings also provide a new strategy for exploring the role of A. argyi in treating ACD.

OBJECTIVE: To observe the clinical effect of nape seven needles combined with pressing moxibustion for cervical vertigo (CV).
METHODS: A total of 70 patients with CV were randomized into an observation group and a control group, 35 cases in each group. In the observation group, nape seven needles combined with pressing moxibustion was delivered, once a day, 6 times a week, for consecutive 2 weeks. In the control group, betahistine hydrochloride tablet and aceclofenac dispersible tablet were given orally, for 2 weeks and 3 days respectively. Before and after treatment, the evaluation scale for cervical vertigo (ESCV) score was observed, the plasma levels of neuropeptide Y (NPY), endothelin-1 (ET-1) and calcitonin gene related peptide (CGRP) were detected, the hemorheologic and hemodynamic indexes were measured, and the clinical efficacy was evaluated after treatment in the two groups.
RESULTS: After treatment, the scores of dizziness, daily life and work ability, psychological and social adaptability, and headache, as well as the total scores of ESCV were increased compared with those before treatment (P<0.01, P<0.05) in the two groups, and the score and total score of neck and shoulder pain of ESCV was increased compared with that before treatment (P<0.01) in the observation group; each sub-item score and total score of ESCV in the observation group were higher than those in the control group (P<0.01, P<0.05). After treatment, the plasma levels of NPY and ET-1 were decreased compared with those before treatment (P<0.01), while the plasma levels of CGRP were increased compared with those before treatment (P<0.01, P<0.05) in the two groups; the plasma levels of NPY and ET-1 in the observation group were lower than those in the control group (P<0.01), the plasma level of CGRP in the observation group was higher than that in the control group (P<0.01). After treatment, the whole blood high shear viscosity, plasma viscosity and whole blood low shear viscosity were decreased compared with those before treatment (P<0.01, P<0.05), the mean velocity of basilar artery (BA), left vertebral artery (LVA) and right vertebral artery (RVA) were increased compared with those before treatment (P<0.05) in the two groups; the whole blood high shear viscosity, plasma viscosity and whole blood low shear viscosity in the observation group were lower than those in the control group (P<0.01), and the mean velocity of BA, LVA and RVA in the observation group were higher than those in the control group (P<0.05). The total effective rate in the observation group was 91.4% (32/35), which was superior to 71.4% (25/35) in the control group (P<0.05).
CONCLUSIONS: Nape seven needles combined with pressing moxibustion can effectively alleviate the clinical symptoms, and improve the hemorheology and hemodynamics in CV patients.
目的：观察项七针联合压灸治疗颈性眩晕（CV）的临床疗效。方法：将70例CV患者随机分为观察组和对照组，每组35例。观察组采用项七针联合压灸治疗，每日1次，每周6次，连续治疗2周。对照组予口服盐酸倍他司汀片（2周）和醋氯芬酸分散片（3 d）。分别于治疗前后观察两组患者颈性眩晕症状与功能评估量表（ESCV）评分，检测血浆神经肽Y（NPY）、内皮素-1（ET-1）、降钙素基因相关肽（CGRP）含量及血液流变学、血流动力学指标，并于治疗后评定两组临床疗效。结果：治疗后，两组患者ESCV眩晕、日常生活及工作能力、心理及社会适应能力、头痛评分及总分较治疗前升高（P<0.01，P<0.05），观察组患者颈肩痛评分较治疗前升高（P<0.01）；观察组患者ESCV各项评分及总分均高于对照组（P<0.01，P<0.05）。治疗后，两组患者血浆NPY和ET-1含量较治疗前降低（P<0.01），血浆CGRP含量较治疗前升高(P<0.01，P<0.05)；观察组患者血浆NPY、ET-1含量低于对照组（P<0.01），血浆CGRP含量高于对照组（P<0.01）。治疗后，两组患者全血高切黏度、血浆黏度、全血低切黏度均较治疗前降低（P<0.01，P<0.05），基底动脉（BA）、左侧椎动脉（LVA）、右侧椎动脉（RVA）平均血流速度均较治疗前升高（P<0.05）；观察组患者全血高切黏度、血浆黏度及全血低切黏度均低于对照组（P<0.01），BA、LVA、RVA平均血流速度均高于对照组（P<0.05）。观察组总有效率为91.4%（32/35），高于对照组的71.4%（25/35，P<0.05）。结论：项七针联合压灸可有效减轻CV患者临床症状，改善血液流变学及血流动力学。.

Spinal cord injury (SCI) represents a profound central nervous system affliction, resulting in irreversibly compromised daily activities and disabilities. SCI involves excessive inflammatory responses, which are characterized by the existence of high levels of proinflammatory M1 macrophages, and neuronal mitochondrial energy deficit, exacerbating secondary damage and impeding axon regeneration. This study delves into the mechanistic intricacies of SCI, offering insights from the perspectives of neuroimmune regulation and mitochondrial function, leading to a pro-fibrotic macrophage phenotype and energy-supplying deficit. To address these challenges, we developed a smart scaffold incorporating enzyme mimicry nanoparticle-ceriumoxide (COPs) into nanofibers (NS@COP), which aims to pioneer a targeted neuroimmune repair strategy, rescuing CGRP receptor on macrophage and concurrently remodeling mitochondrial function. Our findings indicate that the integrated COPs restore the responsiveness of pro-inflammatory macrophages to calcitonin gene-related peptide (CGRP) signal by up-regulating receptor activity modifying protein 1 (RAMP1), a vital component of the CGRP receptor. This promotes macrophage fate commitment to an anti-inflammatory pro-resolution M2 phenotype, then alleviating glial scar formation. In addition, NS@COP implantation also protected neuronal mitochondrial function. Collectively, our results suggest that the strategy of integrating nanozyme COP nanoparticles into a nanofiber scaffold provides a promising therapeutic candidate for spinal cord trauma via rational regulation of neuroimmune communication and mitochondrial function.

OBJECTIVE: Paclitaxel (PTX) is extensively utilized in the management of diverse solid tumors, frequently resulting in paclitaxel-induced peripheral neuropathy (PIPN). The present study aimed to investigate sex differences in the behavioral manifestations and underlying pathogenesis of PIPN and search for clinically efficacious interventions.
METHODS: Male and female C57BL/6 mice (5-6 weeks and 12 months, weighing 18-30 g) were intraperitoneally (i.p.) administered paclitaxel diluted in saline (NaCl 0.9%) at a dose of 2 mg/kg every other day for a total of 4 injections. Von Frey and hot plate tests were performed before and after administration to confirm the successful establishment of the PIPN model and also to evaluate the pain of PIPN and the analgesic effect of PD-L1. On day 14 after PTX administration, PD-L1 protein (10 ng/pc) was injected into the PIPN via the intrathecal (i.t.) route. To knock down TRPV1 in the spinal cord, adeno-associated virus 9 (AAV9)-Trpv1-RNAi (5 μL, 1 × 1013 vg/mL) was slowly injected via the i.t. route. Four weeks after AAV9 delivery, the downregulation of TRPV1 expression was verified by immunofluorescence staining and Western blotting. The levels of PD-L1, TRPV1 and CGRP were measured via Western blotting, RT-PCR, and immunofluorescence staining. The levels of TNF-α and IL-1β were measured via RT-PCR.
RESULTS: TRPV1 and CGRP protein and mRNA levels were higher in the spinal cords of control female mice than in those of control male mice. PTX-induced nociceptive behaviors in female PIPN mice were greater than those in male PIPN mice, as indicated by increased expression of TRPV1 and CGRP. The analgesic effects of PD-L1 on mechanical hyperalgesia and thermal sensitivity were significantly greater in female mice than in male mice, with calculated relative therapeutic levels increasing by approximately 2.717-fold and 2.303-fold, respectively. PD-L1 and CGRP were partly co-localized with TRPV1 in the dorsal horn of the mouse spinal cord. The analgesic effect of PD-L1 in PIPN mice was observed to be mediated through the downregulation of TRPV1 and CGRP expression following AAV9-mediated spinal cord specific decreased TRPV1 expression.
CONCLUSIONS: PTX-induced nociceptive behaviors and the analgesic effect of PD-L1 in PIPN mice were sexually dimorphic, highlighting the significance of incorporating sex as a crucial biological factor in forthcoming mechanistic studies of PIPN and providing insights for potential sex-specific therapeutic approaches.

Active artificial bone substitutes are crucial in bone repair and reconstruction. Calcium phosphate bone cement (CPC) is known for its biocompatibility, degradability, and ability to fill various shaped bone defects. However, its low osteoinductive capacity limits bone regeneration applications. Effectively integrating osteoinductive magnesium ions with CPC remains a challenge. Herein, we developed magnesium malate-modified CPC (MCPC). Incorporating 5% magnesium malate significantly enhances the compressive strength of CPC to (6.18 ± 0.49) MPa, reduces setting time and improves disintegration resistance. In vitro, MCPC steadily releases magnesium ions, promoting the proliferation of MC3T3-E1 cells without causing significant apoptosis, proving its biocompatibility. Molecularly, magnesium malate prompts macrophages to release prostaglandin E2 (PGE2) and synergistically stimulates dorsal root ganglion (DRG) neurons to synthesize and release calcitonin gene-related peptide (CGRP). The CGRP released by DRG neurons enhances the expression of the key osteogenic transcription factor Runt-related transcription factor-2 (RUNX2) in MC3T3-E1 cells, promoting osteogenesis. In vivo experiments using minipig vertebral bone defect model showed MCPC significantly increases the bone volume fraction, bone density, new bone formation, and proportion of mature bone in the defect area compared to CPC. Additionally, MCPC group exhibited significantly higher levels of osteogenesis and angiogenesis markers compared to CPC group, with no inflammation or necrosis observed in the hearts, livers, or kidneys, indicating its good biocompatibility. In conclusion, MCPC participates in the repair of bone defects in the complex post-fracture microenvironment through interactions among macrophages, DRG neurons, and osteoblasts. This demonstrates its significant potential for clinical application in bone defect repair.

Psoriasis is an immune-mediated skin disease associated with neurogenic inflammation, but the underlying molecular mechanism remains unclear. We demonstrate here that acid-sensing ion channel 3 (ASIC3) exacerbates psoriatic inflammation through a sensory neurogenic pathway. Global or nociceptor-specific Asic3 knockout (KO) in female mice alleviates imiquimod-induced psoriatic acanthosis and type 17 inflammation to the same extent as nociceptor ablation. However, ASIC3 is dispensable for IL-23-induced psoriatic inflammation that bypasses the need for nociceptors. Mechanistically, ASIC3 activation induces the activity-dependent release of calcitonin gene-related peptide (CGRP) from sensory neurons to promote neurogenic inflammation. Botulinum neurotoxin A and CGRP antagonists prevent sensory neuron-mediated exacerbation of psoriatic inflammation to similar extents as Asic3 KO. In contrast, replenishing CGRP in the skin of Asic3 KO mice restores the inflammatory response. These findings establish sensory ASIC3 as a critical constituent in psoriatic inflammation, and a promising target for neurogenic inflammation management.

OBJECTIVE: To observe the effect of moxibustion at \"Xinshu\" (BL15) and \"Feishu\" (BL13) on transient receptor potential vanilloid type 1(TRPV1), calcitonin gene-related peptide (CGRP), and serum interleukin-10 (IL-10) in the myocardial tissue of rats with chronic heart failure (CHF), so as to explore its underlying mechanisms in improvement of CHF.
METHODS: Male SD rats were randomly divided into the normal, model, moxibustion, capsaicin, moxibustion + capsaicin, and moxibustion + solvent groups, with 10 rats in each group. The CHF model was established by permanent ligation of the anterior descending branch of the left coronary artery. Mild moxibustion was applied to bilateral BL13 and BL15 for 30 min once daily for 4 weeks. Rats in the capsaicin group were smeared with capsaicin in the acupoint area once a day for 4 weeks. For rats of the moxibustion + capsaicin and moxibustion + solvent groups, capsaicin and solvent were applied to the acupoint area before moxibustion for 4 weeks, respectively. The ejection fraction (EF) and left ventricular fractional shortening rate (FS) were examined by echocardiography. HE staining was used to observe the myecardial morphological structure. The mRNA and protein expression levels of TRPV1, CGRP and galectin-3 (Gal-3) in myocardial tissue were detected by real-time quantitative PCR and Western blot, respectively. The content of IL-10 in serum was detected by ELISA.
RESULTS: After modeling, the pathological changes of myocardium (as cardiac muscle fiber disorder, inflammatory cell infiltration, etc.) were obvious, and the EF, FS, serum IL-10, protein and mRNA exspression of TRPV1 and CGRP were significantly decreased (P<0.01) in the model group compared with the normal group, while the protein and mRNA exspression of Gal-3 were significantly up-regulated (P<0.01). Following the interventions, the above-mentioned indexes were all reversed in moxibustion, capsaicin, and moxibustion + capsaicin groups (P<0.01), and the effect of moxibustion + capsaicin was the best (P<0.05, P<0.01).
CONCLUSIONS: Moxibustion can reduce myocardial injury and improve cardiac function in CHF rats, which may be related to its effects in up-regulating the expression of TRPV1 and CGRP, and down-regulating the expression of Gal-3 to alleviate myocardial fibrosis.
目的: 观察艾灸“心俞”“肺俞”对慢性心力衰竭（CHF）大鼠心肌组织瞬时受体电位香草酸亚型1（TRPV1）、降钙素基因相关肽（CGRP）及血清白细胞介素-10（IL-10）的影响，探讨艾灸“心俞”“肺俞”治疗CHF的作用机制。方法: SD大鼠随机分为正常组、模型组、艾灸组、辣椒素组、艾灸+辣椒素组、艾灸+溶媒组，每组10只。采用冠状动脉左前降支结扎致心肌梗死法制备CHF大鼠模型。艾灸组每日艾灸“心俞”“肺俞” 30 min；辣椒素组每日穴区涂抹辣椒素；艾灸+辣椒素组、艾灸+溶媒组分别将辣椒素、溶媒于艾灸前涂于穴区，艾灸方法同艾灸组。各组均治疗4周。采用小动物彩色多普勒超声仪检测各组大鼠射血分数（EF）及左室短轴缩短率（FS）；HE染色法观察大鼠心肌细胞形态结构；实时荧光定量PCR和Western blot法检测大鼠心肌组织中TRPV1、CGRP、半乳糖凝集素-3（Gal-3） mRNA和蛋白表达水平；ELISA法检测大鼠血清IL-10含量。结果: 与正常组比较，模型组大鼠心肌纤维紊乱，炎性细胞浸润明显，EF及FS降低（P<0.01），心肌TRPV1、CGRP mRNA和蛋白表达水平及血清IL-10含量降低（P<0.01），心肌Gal-3 mRNA和蛋白表达水平升高（P<0.01）。与模型组比较，艾灸组、辣椒素组、艾灸+辣椒素组上述指标均逆转（P<0.01）。与艾灸组、辣椒素组比较，艾灸+辣椒素组效果更佳（P<0.05，P<0.01）。结论: 艾灸“心俞”“肺俞”可以改善CHF大鼠心肌损伤，其作用可能与调控TRPV1通路，升高TRPV1、CGRP mRNA和蛋白表达，促进抗炎因子IL-10上调，降低Gal-3 mRNA和蛋白表达水平，从而减轻心肌纤维化有关。.

Oral squamous cell carcinoma (OSCC) associated pain commonly predicts adverse events among patients. This clinical feature indicates the engagement of nociceptors on sensory neurons during the development of malignancy. However, it is yet to be determined if targeting oncometabolite-associated nociception processes can hinder OSCC progression. In this study, we reported that nociceptive endings infiltrating both clinical samples and mouse tumor xenografts were associated with poorer clinical outcomes and drove tumor progression in vivo, as evidenced by clinical tissue microarray analysis and murine lingual denervation. We observed that the OSCC microenvironment was characteristic of excessive adenosine due to CD73 upregulation which negatively predicted clinical outcomes in the TCGA-HNSC patient cohort. Notably, such adenosine concentrative OSCC niche was associated with the stimulation of adenosine A2A receptor (A2AR) on trigeminal ganglia. Antagonism of trigeminal A2AR with a selective A2AR inhibitor SCH58261 resulted in impeded OSCC growth in vivo. We showed that trigeminal A2AR overstimulation in OSCC xenograft did not entail any changes in the transcription level of CGRP in trigeminal ganglia but significantly triggered the release of CGRP, an effect counteracted by SCH58261. We further demonstrated the pro-tumor effect of CGRP by feeding mice with the clinically approved CGRP receptor antagonist rimegepant which inhibited the activation of ERK and YAP. Finally, we diminished the impact of CGRP on OSCC with istradefylline, a clinically available drug that targets neuronal A2AR. Therefore, we established trigeminal A2AR-mediated CGRP release as a promising druggable circuit in OSCC treatment.