Acupuncture at Feng chi (GB20) and Yang ling quan can improve migraine pain by reducing microglial activation and microglial-mediated inflammatory responses that could be regulated by the toll like receptor 4 (TLR4)/nuclear factor kappa B (NF-κB) pathway (2). 

A similar study with Shai gu (GB8) and Yang ling quan for migraine suffering rats showed pain relief by inhibiting the expression of Cx43 and activation of astrocytes and neurons, and reducing release of pro-inflammatory factor IFN-γ in TNC (3).

In a review of the mechanisms of acupuncture, in animal models, on migraine, researchers found that acupuncture, with the primary points at Feng chi and Yang ling quan, exerts its therapeutic effect on migraine by regulating neurotransmitter release, inhibiting inflammatory responses, modulating central analgesic mechanisms, and suppressing glial cell activation (4).

EA significantly ameliorated the mechanical and thermal hyperalgesia, reduced c-Fos levels in the trigeminal ganglion, and comprehensively attenuated plasma and dural levels of vasoactive neurotransmitters, especially in the multiple acupuncture points group Feng chi (GB20) and Yang ling quan (GB34) in migraine rats. This study showed that the point combination was more effective than those points used individually (5). 

EA at Tai chong (LR3) and Yang ling quan (GB34) mediates analgesia through both opioid and endocannabinoid pathways. TRPM8 is critical for EA to activate the opioid pathway, while its inhibition or deletion shifts the analgesic mechanism towards reliance on the cannabinoid system (6). 

Acupuncture, at Bai hui (DU20), Yin tang (DU24+), Ren ying (ST9), Nei guan (PC6), Yang ling quan (GB34), and moxibustion, at Zhong wan (REN12), Xia wan (REN10), Qi hai (REN6), Guan yuan (REN4), Ge shu (BL17) and Dan shu (BL19), can improve arterial elasticity in patients with early carotid atherosclerosis, and it is safe and effective (7)

Acupuncture at ST9 (ren ying), PC6 (nei guan), GB34 (yang lingquan), DU20 (bai hui) and EX-HN3 (yin tang) was also shown to that acupuncture had a certain effect on reducing the thickness and volume of carotid plaque and improving the stability of plaque with minor side effects (8).

fMRI studies:

• In a review of post-stroke acupuncture, researches found that Yanglingquan (GB34), Baihui (DU20) and Shenting (DU24) were the most commonly used points, treatment was given for 4-8 weeks and manual, electro and scalp acupuncture were all used. The researchers surmised that, ‘acupuncture can potentially facilitate the reversible restoration of impaired neurological functions. This effect may be attributed to stimulating neural cell biological activity in specific brain areas, leading to alterations in neuronal activity, structural reorganization of the brain network, or changes in the strength of functional connectivity within those areas.’ (9)
• Acupuncture at GB34 may increase motor-cognition connectivity meanwhile decrease compensation of unaffected motor cortex and homolateral synkinesis, which can definitely promote the rehabilitation of hemiplegia and spasm (10).
• Electroacupuncture stimulation (EAS) at GB34 appears to be more related to motor function than EAS at its sham point, suggesting specificity of the GB34 acupoint. The results of this study provide neurobiological evidence for the existence of acupoint specificity (11).
• Acupuncture at GB34 triggered intersubject functional correlation among upper limb motor, upper limb/hand/face, lower limb, tongue/larynx sensory, and movement imagination regions in the patient group. Patients had a stronger response if they were in the early stage of post stroke damage, a month or less, or if the post stroke damage was less (12)
• acupuncture at GB34 led to a signal synchronization change of regional homogeneity in the cognitive, motor, default network, limbic system and other parts of encephalic regions (13)
• Stroke patients revealed decreased functional connectivity between the bilateral M1s compared with healthy subjects, and the decreased functional connectivity was significantly enhanced after acupuncture at GB34, a potential mechanism for post stroke recovery (14)
• Researchers doing fMRI on healthy volunteers at Zu san li (ST36) and Yang ling quan concluded that: ‘the results of our neuroimaging study suggest that the combination of acupoints could more widely activated areas of the brain compared to a single acupoint. Additionally, the combination of acupoints can activate some new brain areas and generate new curative effects.’ An critical conclusion when we consider how and why we stack points and the biomechanisms we want to achieve for patients as well as how we even study what biomechanisms are enacted (15)
• ‘left GB34 induced neural responses in the left putamen, caudate body, insula, postcentral gyrus, claustrum, right and left thalamus, right middle frontal gyrus, hypothalamus, and subthalamic nucleus. Acupuncture on the right GB34 induced neural responses in the right middle frontal gyrus, inferior parietal lobule, thalamus, putamen, lateral globus pallidus, medial globus pallidus, and insula. Interestingly, the putamen and insula were ipsilaterally activated by acupuncture on either the left or right GB34; therefore, they seem to be the main target areas affected by GB34 acupuncture. This is the first reported functional magnetic resonance imaging study directly comparing needling on the right and left GB34. Although more replication studies are needed, our preliminary results prove that acupuncture has different modulatory effects on the brain when performed on the right versus left side.’ (16)
• Curiously acupuncture at Yang ling quan activated the hippocampus, thalamus, globus pallidus, caudate body, claustrum, cingulate gyrus, and culmen in males, and the middle and inferior frontal gyrus, precuneus, postcentral gyrus, inferior parietal lobule, superior temporal gyrus, caudate body, insula, fusiform gyrus, cingulate gyrus, amygdala, and parahippocampal gyrus in females. The middle/medial frontal gyrus, middle temporal gyrus, thalamus, globus pallidus, caudate body, uvula, and cerebellar tonsil were activated when data from all subjects were combined. Relative to males, females exhibited greater brain activation in the right-sided postcentral gyrus, precentral gyrus, precuneus, postcentral gyrus, inferior parietal lobule, declinive, middle occipital gyrus and parahippocampal gyrus. This research suggests that men may get stronger motor benefit from Yang ling quan and women may get more emotional and sensory regulation (17)

Spasticity 

Acupuncture at Yang ling quan can also spastic paresis after middle cerebral artery occlusion in rats. Researchers saw improvements in neurological deficit, muscle tone, and cerebral blood flow, alongside up-regulated expressions of GABAAγ2 and KCC2, whose pathway could regulate spasticity. These effects were stronger with waggle needling (18). 

Similarly, acupuncture can alleviate post-stroke spasticity, effectively, which may be related to its effect in up-regulating the expressions of Na+/K+-ATPase and EAATs (GLAST and GLT-1) in the hippocampus. The anti-spastic effect of acupuncture at GB34+GV20 is superior to GB34 alone (19).

In other words, the above study shows acupuncture can relieve spasticity by inhibiting neural excitation that leads to heightened muscle tone whereas this study shows it relieves spasticity by reducing excitotoxicity and hyperexcitability, dampening overactive motor neurons.

Parkinson’s Disease

• Yang ling quan is one of the most commonly used points for Parkinson’s disease, a review found and with other points can lead to protecting dopaminergic neurons and reducing α-synuclein levels, reducing anti-oxidant stress, increasing anti-neuroinflammatory response, up-regulation of neurotrophic factors and reduction of nerve cell apoptosis, down-regulation of endoplasmic reticulum stress and improvement of mitochondrial function, improvement of the function of the ubiquitin-proteasome system, anti-excitatory toxicity response, activation of autophagy, and modulation of gut microbiota (20)
• Acupuncture stimulation at Yang ling quan increases the neural response in regions, including the substantia nigra, caudate, thalamus, and putamen, which are impaired by Parkinson’s disease, and as such, may lead to improvements in symptoms (21, 22).
• Acupuncture at Yang ling quan, in this a mouse model of Parkinson’s disease, did not attenuate tyrosine hydroxylase-immunoreactive neuronal death, depletion of striatal dopamine levels, or reduced striatal tyrosine hydroxylase expression. Our results indicate that acupuncture is not neuroprotective against nigrostriatal loss in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of PD (23).
• Yang ling quan can promote autophagic clearance of α-synuclein (α-syn), a well known aggregation-prone protein closely related to Parkinson’s disease (PD), in the substantia nigra (SN). Curiously, the researchers found that, ‘the protein clearance arose from the activation of the autophagy-lysosome pathway (ALP) in a mammalian target of rapamycin (mTOR)-independent approach. Further, we observed the recovery in the activity of dopaminergic neurons in SN and improvement in the motor function at the behavior level of PD mice. Whereas acupuncture and rapamycin, a chemical mTOR inhibitor, show comparable α-syn clearance and therapeutic effects in the PD mouse model, the latter adopts a distinctly different, mTOR-dependent, autophagy induction process. Due to this fundamental difference, acupuncture may circumvent adverse effects of the rapamycin treatment (24).
• 3 weeks of EA at Yang ling quan to Kun lun (GB60) not only prevented dopaminergic neuronal death in the SN it also restored neurogenesis subventricular zone by upregulating brain derived neurotrophic factor and phosphorylated ERK (pERK) (25). 
• Acupuncture (At Bai hui and Yang ling quan) can improve motor function and increase the number of TH-positive neurons in the SN of PD model mice. Its neuroprotective effect may relate to the regulation of the SATB1/p21 signaling pathway and the inhibition of cellular senescence-related biomarker expression in the SN. Specifically reduced SA-β-gal which means fewer senescent/aged neurons and reduced p21 and p53 (protein & mRNA) which leads to reduced pro-senescence signalling. Thus acupuncture is slowing cellular ageing processes in the substantia nigra (26)
• Acupuncture every other day for a month at Tai chong and Yang ling quan inhibits the increase in ferric iron and the decrease in the F-H that results in PD mice and prevents changes in the presence of ferrous iron and ferritin-light chain (F-L). These results suggest that acupuncture may inhibit iron-related oxidative damage and may prevent the deleterious alteration of iron metabolism which can also lead to dopaminergic neuron damage which drive Parkinson’s pathology (27)

Acupuncture at Zu san li (ST36) and Yang ling quan activates neurons, especially in the somatosensory cortex (S1), as well as astrocytes. There was no response in the motor cortex (M1). The effects were almost instant, showing that they were neuronally transmitted, via, it was shown, activation of calcium transients. Anaesthesia nullified the effects (28). 

10 daily sessions of acupuncture at bilateral He gu (LI4), Nei guan (PC6), Qu chi (LI11), Zu san li (ST36), Yang ling quan (GB34) and San yin jiao (SP6) was shown to promote the motor recovery and modified cerebro-cerebellar voxel-mirrored homotopic connectivity via bilateral static and dynamic reorganisations for ischemic stroke patients with hemiparesis. Thus, acupuncture promoted bilateral reorganisation of motor networks helping the damaged hemisphere re-establish coordination with the intact side and promoting motor recovery. (29)

EA at Gan shu (BL18) and Yang ling quan can ease hepatic reperfusion injury, significantly reducing serum alanine transaminase and aspartate aminotransferase, TNF-α, IL-6, and HMGB1, liver HMGB1 IR-positive cells, protein and mRNA, in essence inflammatory markers, there was a correlated improvement in histological measurements (30). 

Another study found acupuncture at Yang ling quan, similarly, could suppress serum levels of aspartate aminotransferase and alanine aminotransferase, the total cholesterol concentration, and the levels of hepatic thiobarbituric-acid-reactive substance, but that this didn’t necessarily translate into histological improvements, and thus GB34 on it’s own is not sufficient to resolve acute liver injuries (31). 

Yang ling quan is the most effective lower he sea point for cholecystitis. All lower he sea poinst benefitted guinea pigs with cholecystitis, reducing inflammatory markers and increasing repair, though Yang ling quan was the most effective for this. But, only Yang ling quan regulated the nuclear factor-κB pathway in the gallbladder (32). 

Acupuncture has bi-directional effects to gallbladder pressure and sphincter of Oddy function, which is probably due to autonomic reflex and somatovisceral interactions. Manual or electroacupuncture at Tian shu (ST25) or Qi men (LR14) significantly increased the frequency and amplitude of sphincter of Oddy myoelectrical activities and simultaneously decreased the gallbladder pressure. Whereas, manual or electroacupuncture at GB34 or CO11 significantly decreased sphincter of Oddy myoelectricity and increased the gallbladder pressure (33)

Manual acupuncture, with reinforcing technique at GB34 reduced the liver index, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total cholesterol levels in chronic liver damaged rats (34)

A review concluded that, ‘acupuncture has demonstrated safety and efficacy in the treatment of non-alcoholic fatty liver syndrome, significantly improving hepatic function, lowering glucose and lipid levels, and mitigating liver fibrosis and that Yang ling quan is a commonly used point for this (35).

Acupuncture at Zu san li, Yang ling quan, Nei guan (PC6) and Guan yuan (REN4) can adjust immune function in sepsis patients. After six days of treatment, CD3+, CD4+, CD8+, IgG, IgA, IgM, and CD4+ /CD8+ ratio were all significantly increased, the ICU hospitalization length was significantly shortened, and the hospital readmission rate and the 28-day mortality were lower (36)

Acupuncture at Yang ling quan significantly inhibits the up-regulated osteoblastic marker genes mRNA expression induced by lumbar disc degeneration. Compared with the model group, the mRNA levels of Col1, ADAMTS-7 and ADAMTS-12 in acupuncture group were significantly decreased, in contrast, the mRNA levels of Col2 and COMP were increased. The researchers also found that acupuncture treatment significantly improved the mRNA and protein levels of PGRN and TIMP-1, and reduced the levels of MMP13 at both mRNA and protein levels in degenerated lumbar intervertebral discs (IVD). Studies in vitro indicated that PGRN may play a regulation on the expression of TIMP-1, MMP-13, TNF-α, Col1, Col2, COMP, ADAMTS-7 and ADAMTS-12, and may play a pivotal role in the amelioration of LIVD by acupuncture treatment. In conclusion, acupuncture Yanglingquan acupoint could effectively alleviate surgery induced lumbar disc degeneration, and the mechanism may be related to upregulation of PGRN expression and inhibition of NF-κB pathway (37)

Acupuncture at GB34 has protective effects against immobilization-induced muscle atrophy by regulating the activities of apoptosis-associated BAX/Bcl-2 proteins in gastrocnemius muscle (38).

EA (2Hz, 1mA) at, Shen shu (BL23), Huan tiao (GB30), Wei zhong (BL40) and Yang ling quan (GB34) can effectively reverse the abnormal excitability of sensory neurons in the dorsal horn of the spinal cord, improve the plantar mechanical pain threshold and inflammatory factors in discogenic sciatica rat models (39).

Acupuncture at Inner knee eye (EX-LE4), outer knee eye (EX-LE5), Yanglingquan (GB34), and Zusanli (ST36) can reduce pain and improve knee joint function in part by regulating the p38 MAPK signaling pathway in patients with osteoarthritis of the knee (40)

Unilateral EA (2/100Hz, 2mA), 5 times a week for 2 weeks, at Yang ling quan (GB34) and Nei xi yan (EX-LE4) on the affected side can benefit rats with osteoarthritis of the knee, reducing pain levels as well as the levels of pain-related factors PGE2, CGRP and SP in the DRG and spinal dorsal horn (41)

EA at Huan tiao (GB30), Yang ling quan (GB34), and Xuan zhong (GB39) elevated the serum levels of estradiol and superoxide dismutase, genes associated with bone formation and regulation of the of the PI3K–Akt pathway, thus regulating cell survival, metabolism, growth, and inflammation (42).

Acupuncture, daily for 12 weeks, at Yang ling quan (GB34), Zu san li (ST36) and Xuan zhong (GB39) can benefit rheumatoid arthritis in rats. Reducing inflammatory markers serum TNF-α, IL-6 and IL-17, and the expression levels of mt-p53 and NF-κB p65 proteins (both of which can drive inflammation when heightened) while PPARγ protein was upregulated and can be an anti-inflammatory signaller (43). 

EA, 5 times a week for 8 weeks, at Xue hai (SP10), Zu san li (ST36), Qi xue (KI13) and Yang ling quan (GB34) can effectively alleviate aging-related bone loss and improve the microstructure of bone tissue in senile osteoporosis rats, and the regulation of autophagy might be one of the important mechanisms. The researchers noted serum N-terminal telopeptide of type I collagen (NTX1) level in the EA group was lower, and the serum procollagen type I N-terminal propeptide (PINP) concentration was higher. In addition, the expression of Beclin 1, microtubule-associated protein I light chain 3 (LC3B) and P62 was inhibited in the senile osteoporosis rats after EA treatment (44).

EA, 5 times a week for 8 weeks at Zu san li, San yin jiao (SP6), Yang ling quan and Xue hai,  may prevent bone loss and deterioration in aged rats by promoting osteogenesis via a mechanism that may involve activation of the Wnt/β-catenin signaling pathway. Runx2 and Osterix mRNA and protein levels were significantly increased and peroxisome proliferator-activated receptor (PPAR)γ was significantly decreased in bone marrow cells, while mRNA and protein levels of core constituents of the Wnt/β-catenin signaling pathway (Wnt3a, low-density lipoprotein receptor-related protein (LRP)5 and β-catenin) were significantly increased and Dickkopf 1 was significantly decreased in bone marrow cells (45).

3 daily acupuncture treatments at He gu (LI4), Zhi gou (SJ6), Zu san li (ST36), and Yang ling quan (GB34) can reduce pain intensity and pain on deep breathing in patients with truamatic rib fractures. In this study the use of analgesics was not reduced, though it was a very limited treatment dosage. There was some evidence of reduced GI issues and shortened hospital stays, although they did not reach statistical differences (46)

A study compared the effects of acupuncture at ST36, GB34, and ST36+GB34 on obese rats who were developing osteoarthritis. It has been shown the acupuncture can mitigate the pathogenesis of osteoarthritis, but not whether it can mitigate obesogenic osteoarthritis, which is triggered by lower HDL and higher oxidised LDL that can trigger release of MMPs  (a family of compounds that are catabolic/destructive to cartilage tissue). ‘The results showed that the three acupuncture protocols both prevented obesity-induced cartilage matrix degradation and MMP expression and mitigated obesity-induced systemic and local inflammation but had different regulatory effects on lipid metabolism and gut microbiota disorder of obese-induced OA rats. Furthermore, the three acupuncture protocols increased the microbial diversity and altered the structure of the community of feces in obese rats. We found that ST36 and GB34 could inhibit proinflammatory shift in the gut microbiome with an increase in the ratio of Bacteroidetes/Firmicutes and promote the recovery of relative abundance of Clostridium, Akkermansia, Butyricimonas, and Lactococcus. Although both ST36 and GB34 had an anti-inflammatory effect on serum inflammatory mediators, only the acupuncture protocol with both ST36 and GB34 could effectively inhibit LPS-mediated joint inflammation in obesity rats. Therefore, relieving obesity-related chronic inflammation, lipid metabolism disorder, and gut microbiota disorder may be an important mechanism for acupuncture with ST36 and GB34 to promote OA recovery’ (47)

EA (2 Hz, 0.5—1.5 mA) at Huan tiao (GB30) and Yang ling quan can effectively improve the pain and anxiety behaviors in chronic constriction injury (CCI) rats, and reverse the abnormal expression of SP, NK1R and ARRB1 proteins in the hippocampus, which may be related to its effects in regulating the SP/NK1R/ARRB1 pathway in the hippocampus (48).

Additional researchers went further, looking at all of the protein changes in the hippocampus for neuropathic pain rats when using Zu san li and Yang ling quan. After 12 sessions they noted 19 proteins with significant changes (two-fold+ differences). ‘The top three canonical pathways identified were “cysteine metabolism”, “valine, leucine, and isoleucine degradation” and “mitogen-activated protein kinase (MAPK) signaling”.’ (49)

Further proteomic research into the same condition with the same points but this time in the hypothalamus showed, ‘there were 17 hypothalamic proteins identified with significant changes in the expression (>twofold). Three gene-ontologies (oxidoreductase activity, oxidation reduction, and protein binding) were enriched, while there was a significant regulation of glycolysis/gluconeogenesis/hexose metabolism pathway’. Thus, benefitting pain via multiple pathways (50).

Another study on CCI rats, with Zu san li and Yang ling quan, found percentages and activity of splenic NK cells, concentrations of splenic interleukin-2 (IL-2) and beta-endorphin (β-EP) were significantly increased. Meanwhile, the concentrations of plasma IL-2, IL-1β and gamma-interferon (IFN-γ) were significantly decreased and returned to the normal level on day 12 following EA. Plasma transforming growth factor-β (TGF-β) levels were considerably upregulated on day 5 and 12 following EA. The CD4+/CD8+ T cell ratio was markedly downregulated. After depleting the NK cells the pain relieving benefits of acupuncture were obviously reduced, showing natural killer cells as a mediator of the pain response in neuropathic pain rats (51)

Zu san li and Yang ling quan also regulate the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway to mitigate neuropathic pain in the spinal cord. (52)

They also regulate the expression of TLR4 in the spinal cord neurons and microglia which may partly mediated by spinal microglial KOR and the activation of spinal κ-opioid receptor (KOR) of microglia may be a target for inhibition of microglial TLR4-induced pro-inflammatory signaling (53, 54)

After 4 successive days of acupuncture at Zu san li and Yang ling quan the hippocampal mitogen-activated protein kinase signaling pathway is activated. Which is crucial for Learning and memory formation, cell survival and neuroprotection, stress and inflammation regulation and feeds into the PI3K–Akt–mTOR pathway. (55)

Hippocampal M1 mAChR and β2 nAChR proteins are also regulated by the above points in neuropathic pain and are likely mediators of the pain reduction (56).

The most commonly used experimental approach for treating sciatic nerve injury is once per day lasting for more than 2 weeks, electroacupuncture at 2/100Hz, and the most commonly selected acupoints were Huan tiao (GB30), Zu san li (ST36), and Yang ling quan. The review noted improvements in growth factors, inflammatory markers, myelin sheath, axon and Schwann cells, muscle morphology, enzymes and peptides and angiogenesis (57).

One study, using Huan tiao and Yang ling quan used a deep sequencing analysis to see which miRNA’s were differently expressed in spinal cord damaged rats. They noted one upregulated and five downregulated miRNAs in the model group and  two upregulated miRNAs after EA. They speculated that the upregulation of miR-7a-5p and miR-233-3p is involved in the analgesic effects. MiR-7a-5p is known to suppress NF-κB signalling and pro-inflammatory cytokines, thus reducing neuroinflammation and neuronal hyperexcitability. MiR-223-3p regulates NLRP3 inflammasome activity and downstream release of IL-1β, its upregulation reduces microglial activation and neuroinflammation in the spinal cord (58). 

EA at Zu san li and Yang ling quan can significantly reduce pain in spinal nerve injury rats some of which was mediated by suppressed microglia activation and phosphorylation of JAK2/STAT3 in the L4-6 spine of rats and infiltration of Th2 and secretion of IL-10 in the L4-6 spine of rats with SNI (59)

Acupuncture treatment at Huan tiao (GB30), Yang ling quan (GB34), and Wei zhong (BL40) facilitate functional recovery post sciatic crushed nerve injury. C-Fos and nitric oxide synthase expressions in the brain and BDNF and TrkB expressions in the sciatic nerve were decreased by acupuncture treatment. Huan tiao was the most potent of the above points (60).

Another study found that Huan tiao with Yang ling quan promoted the recovery of motor and electrophysical functioning in sciatic nerve injuries. Mechanisms include regeneration through greater remyelination via increased  myelin basic protein (MBP), neurofilament-200 (NF200), p75 neurotrophin receptor (p75NTR), and growth associated protein-43 (GAP43) (61).

EA of Jia ji (EX-B2), GB34 and EX-B2 + GB34 all has a good analgesic effect in chronic radicular pain (CRP) rats, which may be realized partially by suppressing the release of substance P (SP) in the spinal cord. No significant differences were found among local acupoint, distal acupoint and local plus distal acupoint groups in relieving CRP, improving motor and decreasing SP expression (62).

Acellular nerve allografts combined with electroacupuncture at Huan tiao(GB30) and Yang ling quan (GB34) can enhance sciatic nerve conduction velocity, improve the morphology of neurons in spinal ganglia and play a protective effect on spinal ganglia.The mechanism can be related to the higher expression of nerve growth factor (NGF) and BDNF proteins,especially the expression of NGF protein (63)

EA at Yang ling quan and Xuan Zhong can alleviate anxio-depression-like behaviors induced by neuropathic pain through the modulation of glutamatergic neuron activity in the ventrolateral orbital cortex in mice with common peroneal nerve ligation (64)

Chronic pain can induce extensive damage to the central and peripheral nervous systems. Meanwhile, EA (2/100Hz, 1-2mA) at Zu san li and Yang ling quan and pregabalin can both alleviate chronic pain syndromes in rats, but EA also restores the normal cellular structures, while pregabalin is associated with no improvement (65)

Acupuncture at Yang ling quan and Shui gou (DU26)  inhibits Jun-N-terminal kinase (JNK) activation in astrocytes at L4-L5 level of the spinal cord. The level of p-c-Jun, a downstream molecule of JNK, was also decreased by AP. In addition, SCI-induced GFAP expression, a marker for astrocytes, was decreased by AP as compared to control groups. These benefits and pain relief were reversed when a JNK inhibitor was used (66)

EA at Zu san li and Yang ling quan not only improves muscle function, but also increases miR-181 in serum exosomes and increases renal blood flow, suggesting that miR181 may regulate renal blood flow possibly by influencing the renin-angiotensin system (67)

7 days of EA (2-15Hz, 1-2mA) pretreatment at Nei guan (PC6), T4-T5 Jia ji (EX-B2), Yang ling quan (GB34), or Qu chi (LI11) was investigated for its benefits in preventing post heart attack reperfusion injury. The researchers found that Jia ji specifically modulated the neural-immune network, by looking at the genome wide response, and via that could prevent reperfusion injury, reducing inflammation, fibrosis and increasing oestrogen and testosterone (which protect against coronary heart disease). As well as increasing (GABA) secretion, peripheral nervous system axon regeneration, and ganglion development. Neiguan (PC6) has a high consistency with Jiaji (EX-B2), and both groups have steroid hormone to protect the myocardium during I/R. Nei guan also regulates cardiac muscle contraction, vascular smooth muscle contraction, hypertrophic cardiomyopathy, oxidative phosphorylation, inflammation and immune response, and apoptosis pathways and circadian rhythm genes. Nei guan also has a much stronger, or even, unique benefit to regulate the IL-33 pathway which regulates myocardial fibrosis. Yang ling quan, whilst being able to regulate nervous system development and sex hormone regulation, was not able to prevent ischemia/reperfusion injury. EA pretreatment at LI11 suppressed cell cycle gene expression and activated nervous system signal transduction and gastric acid secretion in I/R rats (68). 

EA at Zu san li to Yang ling quan doesn’t increase pain thresholds in incisional neck pain rats. Nor does it upregulate GABAergic inhibitory modulation on nociceptive peptidergic neurons and stellate glial cells or in the cervical dorsal root ganglion. Whereas, Fu tu (LI18) and/or He gu (LI4) – Nei guan (PC6) do (69). 

Curiously, EA at ST36-GB34 also does not regulate GLAST or GLU-1 in acute incisional neck pain, yet GB34 has been shown to regulate this in migraine and spasticity (70). 

Myocardial ischemia-reperfusion injury leads to myocardial pathological changes as swollen, disorganized arrangement, and partially ruptured myocardial fibers with unclear limit and necrosis and infiltration of lots of inflammatory cells under microscope, and focal myofilament degeneration, dissolution and necrosis with interstitial edema, vague mitochondria with swelling and vacuolation, ruptured and disorganized arrangement of crests. Electroacupuncture at Jia ji or Nei guan can reduce these pathological changes. Qu chi or Yang ling quan do not. Yang ling quan did regulate myocardial CYP1A1 and CYP4A2 proteins but not CYP2B2, CYP2C11 (71)

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