Autonomic Nervous System (ANS) Immune System (IS ...Autonomic NS, Immune S, Inflammation and Local Anesthetics. Neural Therapy as a treatment option Neural Therapy David Vinyes, Sabadell

DDaavviidd VViinnyyeess, MD · Sabadell (Barcelona) · March [email protected] · @david.vinyes

International Federation of Medical Associations of Neural Therapy

Member of Scientific and Ethics CommissionInternational RepresentativePresidentMedical Director Director of Master Degree in Neural Therapy and Neurofocal Dentistry

AAuuttoonnoommiicc NNeerrvvoouuss SSyysstteemm ((AANNSS))

IImmmmuunnee SSyysstteemm ((IISS))

IInnffllaammmmaattiioonn ((IINNFFLL))

aanndd LLooccaall AAnneesstthheettiiccss ((LLAA))

NNeeuurraall TThheerraappyy ((NNTT)) aass aa ttrreeaattmmeenntt ooppttiioonn

AAuuttoonnoommiicc NNeerrvvoouuss SSyysstteemm

IImmmmuunnee SSyysstteemm

IInnffllaammmmaattiioonn

aanndd LLooccaall AAnneesstthheettiiccss

NNeeuurraall TThheerraappyy aass aa ttrreeaattmmeenntt ooppttiioonn

DDiissccllaaiimmeerr:: All advice given out by David Vinyes is for general guidance mainly addressed to physicians and with informational purposesonly. Readers are encouraged to confirm the information provided with other sources. Patients and consumers should review theinformation carefully with their professional health care provider. The information is not intended to replace medical advice offered by otherphysicians. David Vinyes will not be liable for any direct, indirect, consequential, special, exemplary, or other damages arising therefrom.

DDeessccaarrggoo ddee rreessppoonnssaabbiilliiddaadd:: Todos los consejos dados por David Vinyes son sólo para orientación general dirigida fundamentalmente amédicos y con propósitos informativos. Se anima a los lectores a confirmar la información proporcionada con otras fuentes. Los pacientes ylos consumidores deben revisar la información cuidadosamente con su proveedor de atención médica profesional. La información nopretende sustituir el consejo médico ofrecido por otros médicos. David Vinyes no será responsable de ningún daño directo, indirecto,consecuente, especial, ejemplar o de otro tipo que surja de ello.

DDaavviidd VViinnyyeess, MD · Sabadell (Barcelona) · March [email protected] · @david.vinyes

3

Fundamental structures in homeostasis and the connection between organs and tissues

Autonomic NS, Immune S, Inflammation and Local Anesthetics. Neural Therapy as a treatment option

Dav

id V

inye

s, S

abad

ell (

Barc

elon

a) 2

020

Fascial System

Autonomic Nervous System

ExtrecallularMatrix

4

Confocal laser endomicroscopy (pCLE) provides real-time histologic imaging of humantissues at a depth of 60–70 μm depth during endoscopy.

Rather than being densely-packed barrier-like walls of collagen, the submucosa,dermis, fascia, and vascular adventitia are fluid-filled interstitial spaces. The presenceof fluid has important implications for tissue function and pathology.


Dav

id V

inye

s, S

abad

ell (

Barc

elon

a) 2

020

Benias PC et al. . Sci Rep. 2018 May 10;8(1):7610

Is important to emphasize that capillary circulation plays a fundamental role as a transport system in all immunological and metabolic processes. Barop H, 2017. Textbook and atlas of neural therapy: diagnosis and therapy with local anesthetics. Thieme

5


Honoring Alfred Pischinger, head of Histology and Embryology, Univ of Vienna, in 1975 published The Extracellular Matrix (ECM) and Ground Regulation.

Pisc

hing

erA.

The

extr

acel

lula

rmat

rixan

d gr

ound

regu

latio

n. 1

975

Dav

id V

inye

s, S

abad

ell (

Barc

elon

a) 2

020

Extracellular Matrix

The ECM is a three-dimensional network that encompasses all the organs, tissues andcells of the organism, playing a fundamental role in the protection, nutrition and cellularinnervation and is the terrain where the immune response, angiogenesis, fibrosis andtissue regeneration take place.

The alteration of the ECM will also conduct to the loss of the substrate for a correctimmune response to infectious, tumor and toxic agents.


David Vinyes, Sabadell (Barcelona) 2020

RRiicckkeerr observed that an increase in perivasal S tone causes contraction of the precapillariesand dilation of the capillaries with a decrease in blood flow and consequent INFL. This isone of the main points where LA can have a therapeutic action because its sympathicolyticeffect relaxes the muscle of the precapillary artery wall, which greatly increases thecapillary flow rate and the edema can be reabsorbed.

Ricker's Pathology of Relations

Pavlov, Schleich, Head, Spiess, Einhorn, Braun, Leriche, Fontaine, Mackencie, Ricker,Speransky, Vichnevsky, Hansen, Von Staa, Bykow, Sthor, Scheidt, Nonnenbruch, Kibler,Selye, Pischinger, Albanese, Bergsmann, Hopfer, Ujtomsky, Luria, Wedensky,Sechenov, Huneke, etc.



For more than a century, many physicians and surgeons dedicated a great part oftheir lives to investigate the role of the Nervous System (NNSS) in the pathologicalprocess. There were hundreds of articles and treaties on this topic that are still valid.

• Active research in immunology and neuroscience has identified multiple points of interactionand communication between the immune system (IISS) and the NNSS.

• Immune cell activation stimulates neuronal circuits that regulate innate and adaptive immunity.

• Molecular mechanistic insights into the inflammatory (IINNFFLLYY) reflex and other neuro-immuneinteractions have greatly advanced understanding immunity, and identified new therapeuticpossibilities in inflammation ((IINNFFLL)) and immune diseases.


Chavan SS, Immunity. 2017 Jun 20;46(6):927-942.



9


• The AANNSS is a complex network of neurons andnerve pathways that maintains homeostasisof the body and performs adaptive responsesto changes in the external and internalenvironment.

• Innervates the smooth muscles, myocardium,organs, blood vessels and glands (bothexocrine and endocrine) of the whole body.(Jänig W. Auton Neurosci. 2014;182:1–3)


From Pearson Education. Inc

10

o metabolism, reproduction, gastrointestinaltract lining, glandular secretion and bodytemperature.

o vascular, respiratory, digestive, hormonal,musculoskeletal, memory phenomena…

• This homeostasis is carried out by balancingits sympathetic (SS), parasympathetic (PPSS) andenteric branches that allows the simultaneousregulation and coordination of vital functionssuch as: (Jänig W. Auton Neurosci. 2014;182:1–3)


Autonomic NS, Immune S, Inflammation and Local Anesthetics. Neural Therapy as atreatment option



Catecholamines:A, DA, NA

Increases effector organ activity

Sympathetic

Promotes recuperation

Facilitates digestions and

gut motility

Parasympathetic

Slows heart rate

Cholinergic

Adrenergic

Adrenergic

Cholinergic

Cholinergic

Cholinergic

Cholinergic


David Vinyes, Sabadell (Barcelona) 2020Auto

nom

ic N

S, Im

mun

e S,

Infla

mm

atio

n an

d Lo

cal A

nest

hetic

s. N

eura

l The

rapy

as

trea

tmen

t opt

ion

12

TThhee aalltteerraattiioonn ooff tthhee AANNSS ccaann iimmppllyy aannaalltteerraattiioonn ooff tthhee rreegguullaattiioonn of the tissues that itcontrols, affecting its function and leading topathology. (Buijs RM. Handb Clin Neurol. 2013;117:1–11)

Especially in repeated, chronic or associatedprocesses. (Bellinger DL, Lorton D. Auton Neurosci. 2014;182:15–41)

Its clinical manifestations can be multiple andvaried, and often go unnoticed in clinicalpractice. (Navarro X. Rev Neurol. 2002;35(6):553–562)





Dav

id V

inye

s, S

abad

ell (

Barc

elon

a) 2

020



The balance of activity of its SS and PPSS branches has a key part the regulation of bloodpressure, heart rate, myocardial contractility and coronary perfusion.

For instance, an imbalance in the autonomic cardiac fibers can, for example, lead to cardiacarrhythmias.

An imbalance of the SS and PPSS branches of the AANNSS, can also cause and maintain IINNFFLL andpain. Puente de la Vega Costa K et al.. Effects on hemodynamic variables and echocardiographic parameters

after a stellate ganglion block in 15 healthy volunteers. Auton Neurosci. 2016;197:46–55

Model of the metabolic syndrome caused by desynchronization

The disturbed output resulting from lifestyle changes andexcessive food intake affects the balance of the AANNSS.

In intra-abdominal compartment, prevails the PPSS branch(bblluuee), increasing insulin secretion and growth of intra-abdominal fat tissue compared with normal values (ggrraayy).

In thorax and movement compartment, the SS branch (rreedd)prevails, increasing blood pressure and impairing glucoseuptake by the muscle.

In this model, the symptoms of the metabolic syndromeare the result and not the cause of the disease. Reproduced from Kreier et al, 2003, in Buijs RM. The autonomic

nervous system: A balancing act. Handb Clin Neurol. 2013;117:1-11




Patients with acute SARS-CoV illness have also demonstrated the presence of the virus incerebrospinal fluid.

The dissemination of COVID-19 in the systemic circulation or across the cribriform plate ofthe ethmoid bone during an early or later phase of the infection can lead to cerebralinvolvement as has been reported in the past for SARS-CoV affected patients.

Although the cerebral damage may complicate a COVID-19 infection, it appears that it is thewidespread dysregulation of homeostasis caused by pulmonary, renal, cardiac, andcirculatory damage that proves fatal in COIVD-19 patients.




Baig AM, Khaleeq A, Ali U, Syeda H. Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic Mechanisms. ACS Chem Neurosci. 2020 Mar 13.

Reflex Response to Nociceptive Stimuli

Nociceptive processes trigger a reflex response that is mediated predominantly

by the SS system and occurs via cutivisceral, viscerocutaneous,

viscerosomaticmotor and reflex tracts.


Autonomic NS, Immune S, Inflammation and Local Anesthetics. Neural Therapy as treatment option

Sympathetic Reflex

Lorenz Fischer, 2019. Neuraltherapie. Neurophysiologie, Injektionstechnik und Therapievorschläge

In the corresponding projection zones,this can lead to pain, increased muscletone, and dysregulation of the associatedinternal organ, as well as changes incirculation, increased skin turgor, andhyperalgesia of certain skin areas(peripheral sensitization). This furtherincreases the SS activity (+ feedback).



Sympathetic Reflex

Reflex Response to Nociceptive Stimuli

Lorenz Fischer, 2019. Neuraltherapie. Neurophysiologie, Injektionstechnik und Therapievorschläge. Georg Thieme Verlag KG

18

The FFaasscciiaa SSyysstteemm ((FFSS)) is equally distributedthroughout the entire body, enveloping,interacting with, and permeating blood vessels,nerves, viscera, meninges, bones, and muscles,creating various layers at different depths..(Adstrum S, et al. J Bodyw Mov Ther. 2017;21(1):173–177)


Fascial System


FFSS forms a tridimensional metabolic and mechanical matrix

Also has defensive (participates in the immune and IINNFFLLYYresponse), trophic and genetic morpho (influences thegrowth and differentiation of the surrounding tissues)functions.(Dalmau-Santamaria, in Tutusaus R, Potau JM, 2015. Sistema Fascial. Panamericana)

Nerve fibres were found in all samples of visceral fasciae (thorax, lung, oesophagus, heart,liver, kidney, abdomen).

The fasciae closely related to the individual organ and giving shape to it (investing fasciae),supporting the parenchyma, are thin, elastic and very well innervated.

The fibrous sheets forming the organ compartments and also connecting the internal organsto the musculoskeletal system (insertional fasciae), are thick, less elastic and less innervated,but they contain larger and myelinated nerves.

Dav

id V

inye

s, S

abad

ell (

Barc

elon

a) 2

020


Tutu

saus

R, P

otau

JM, 2

015.

Si

stem

a Fa

scia

l. Pa

nam

eric

ana

Stecco C at al. Microscopic anatomy of the visceral fasciae. J Anat. 2017;231(1):121–128.

There is a close relationship between the endocannabinoid or endorphin system and thefibroblasts. The cannabinoid receptor, or CB1, is mainly housed in the NNSS, but it can befound in the FFSS and in the fibroblasts as well, near the neuromuscular junction.

This relationship is believed to better manage any IINNFFLL and pain information originating inthe FF tissue, as the FF undergoes continuous remodeling during the day.

Stimulation of the SS NNSS releases cytokine TGF-b1 which causes an immune systemresponse and a potent myofibroblast contraction.

20

Bordoni B, Zanier E. Clinical and symptomatological reflections: the fascial system.J Multidiscip Healthc. 2014; 7: 401–411

The fascial continuum is innervated by the SS system



Fascial System

21


Fascial System

The great proportion of SS fibers in thoracolumbar fascia in our specimen is surprising.

40% of the entire thoracolumbar fascia innervation consisted of postganglionic SS fibers.Probably the majority of these fibers are vasoconstrictors.


Mense S. Innervation of the thoracolumbar fascia. Eur J Transl Myol. 2019;29(3):8297.

22

Emotional stress disrupts the normative autonomic function


Dav

id V

inye

s, S

abad

ell (

Barc

elon

a) 2

020

Neuro-Inflammation


Emotions

23

All the emotional states are accompanied by concomitant vegetative reactionsimpossible to separate. Czura CJ, Tracey KJ. Autonomic neural regulation of immunity. J Intern Med. 2005;257(2):156–166.

AANNSS also regulates the communication between the nervous system (NNSS) and immune

system (IISS). Vernino S. Autoimmune Autonomic Disorders. Continuum (Minneap Minn). 2020;26(1):44–57




Higher intensities of subjective emotional experience, both positive (e.g., amusement)and negative (e.g., amplified disgust) elicit higher SS responses (Low Frequency Area),whereas emotional regulation is mediated primarily by fluctuations in PPSS activity(Respiratory Frequency Area).

Some studies suggest that the vagal tone is a physiologic index of stress.



Neural Therapy, ANS and Fascia in Psychosomatic ConditionsAutonomic NS, Immune S, Inflammation and Local Anesthetics. Neural Therapy as a treatment option

Brain and body are coupled by the ANS. Emotions evoke “top-down” autonomic responses andare shaped by “bottom-up” afferent somatic feedback.

Emotional stress disrupts normative autonomic function, typically through sympathoexcitation(Owens AP et al. In Reference Module in Neuroscience and Biobehavioral Psychology. Elsevier. 2017)


Early-life adversity, psychosocial stress, age and infection can activate microglia and nneeuurroo--IINNFFLL..

NNeeuurroo--IINNFFLL is now thought to underlie many psychiatric disorders including depression, anxiety,and schizophrenia as well as pain. (reviewed in Skaper et al. 2018).

Neural Therapy, ANS and Fascia in Psychosomatic Conditions

Lurie DI. An Integrative Approach to Neuroinflammation in Psychiatricdisorders and Neuropathic Pain. J Exp Neurosci. 2018 Aug


Integrated therapies that include drug therapy as well as mind/body and plant-based therapieswill likely be the most successful approach for reducing nneeuurroo--IINNFFLL and ameliorating CNSdysfunction.

Dav

id V

inye

s, S

abad

ell (

Barc

elon

a) 2

020

27

Autonomic regulation of Cellular Immune FunctionNeural control of Inflammation


Dav

id V

inye

s, S

abad

ell (

Barc

elon

a) 2

020

Immune System

VagusNerve

Sympathetic System

SS fibers form basket-like structures in the dorsal rootganglia of the nociceptive afferents under inflammatoryconditions. In terms of positive feedback, additionalminor stimuli (peripheral or central) may be sufficient inthis situation to evoke severe pain.

Anti-TH immunostaining of sympathetic fibers in wholemount DRG. Sympathetic nerve fibers could beobserved on the dorsal (top) and ventral (bottom)surfaces of both normal (A, B) and axotomized (C, D)DRGs, however, the axotomized DRGs had much higherfiber density on both sides of the ganglion. Scalebar=200μm.

Sprouting

The SS NNSS plays an important role in the emergence and maintenance of inflammation and chronic pain.


Xie W, et al. Sympathetic sprouting near sensory neurons after nerve injury occurs preferentially onspontaneously active cells and is reduced by early nerve block. J Neurophysiol. 2007;97(1):492–502.

The SS NNSS influences immunological processes

Chavan et al. “Mechanisms and therapeutic relevance of neuro-immune communication”.Immunity. 2017 June 20; 46(6): 927–942.

Pathogens or tissue injury results in the release ofinflammatory (IINNFFLLYY) mediators, such as somecytokines, TNF, IL, nerve growth factor (NGF), PG,serotonin and histamine, by immune cells.

Both pathogens and IINNFFLLYY mediators canmodulate the activity of sensory neurons in thelocal area, acting on receptors expressed onperipheral axonal terminals.

MMoolleeccuullaarr mmeecchhaanniissmmss aatt tthhee iimmmmuunnee--sseennssoorryy nneeuurroonn iinntteerrffaaccee



Neuronal activation by pathogens (similar toimmune activation) and IINNFFLLYY stimuli also causesthe release of neuropeptides, which modulateIINNFFLLYY responses.

VIP, substance P and calcitonin gene-relatedpeptide (CGRP) are involved in the generation ofneurogenic IINNFF.

CGRP, somatostatin and galanin suppresslymphadenopathy and IINNFF in bacterial infection.



The SS NNSS influences immunological processes

Chavan et al. “Mechanisms and therapeutic relevance of neuro-immune communication”.Immunity. 2017 June 20; 46(6): 927–942.


Wiring of the inflammatory reflex

Tracey KJ. The inflammatory reflex. Nature. 2002;420(6917):853–859.

INFLY products produced in damaged tissuesactivate afferent signals to the NTS.

Efferent activity in the vagus nerve leads toacetylcholine (ACh) release, activating Ach-Receptor on tissue macrophages, which inhibit therelease of TNF, IL-1, HMGB1 and other cytokines.

The release of ACTH from hypothalamus andactivation of the S outflow modulate also INFL.




Tracey KJ. The inflammatory reflex. Nature. 2002;420(6917):853–859.



Vagal nerve stimulation seems to restore the body’s naturalbalance. It reduces the over-production of TNF that causeschronic IINNFFLL but does not affect healthy immune function, sothe body can respond normally to infection.

Both SS and PPSS arms of the AANNSS are instrumental in orchestrating neuroimmune processes.




Jänig, W. (2006). Integrative Action of the Autonomic Nervous System: Neurobiology of Homeostasis. Cambridge: Cambridge University Press



Recent basic science research has demonstrated that a neural reflex (inflammatory reflex),modulates systemic and regional IINNFFLL in a multiplicity of clinical conditions encountered inperioperative medicine and critical care, like sepsis, ventilator-induced lung injury,postoperative cognitive dysfunction, myocardial ischemia–reperfusion injury, and traumatichemorrhage.

These new insights might spawn novel therapeutic strategies for the treatment of inflammatory diseases in the context of perioperative and critical care medicine.

Steinberg BE, Sundman E, Terrando N, Eriksson LI, Olofsson PS. Neural Control of Inflammation: Implications forPerioperative and Critical Care. Anesthesiology. 2016;124(5):1174–1189.

35

Histofluorescent demonstrates noradrenergic (NA) innervation of the thymus, spleen and lymph nodefrom rodents. (A) Thymic NA nerves derive from the superior cervical and stellate ganglia and formneurovascular plexuses. (B) NA fibers enter the spleen around the splenic artery (ca), and travel with thevasculature in plexuses. (C) NA innervation of a popliteal lymph node (PLN) showing fluorescent NAnerves traveling along a blood vessel (BV).



Bellinger DL, Lorton D. Autonomic regulation of cellular immune function. Auton Neurosci. 2014;182:15–41

36

EEffffeeccttss ooff ββ--aaddrreenneerrggiicc rreecceeppttoorr ((AARR)) ssttiimmuullaattiioonn oonn aannttiiggeenn--pprreesseennttiinngg cceellll ((AAPPCC:: ddeennddrriittiicc cceellllss,,mmaaccrroopphhaaggeess oorr BB--cceellllss)) aanndd TT--cceellll. Simultaneous TCR recognition of a specific MHC-Ag complexand B7 by CD28 induces gene transcription ((ggrraayy aarrrroowwss)) in both the T-cell and the APC, whichdirects specific cellular responses (immune response). Activation of β-ARs via nnoorreeppiinneepphhrriinnee((ggrreeeenn cciirrcclleess)) binding directly effects gene transcription in the APC or the T-cell, and thesubsequent changes in gene transcription ((ggrreeeenn aarrrroowwss)) which influences their cellularresponses.



37

DDiirreecctt aanndd iinnddiirreecctt eeffffeeccttss ooff AARR ssttiimmuullaattiioonn wwiitthh nnoorreeppiinneepphhrriinnee oonn AAPPCC aanndd TT--cceellll.Additionally, β-AR-mediated changes in the cellular response of the APC can indirectly affectT-cell response ((bblluuee aarrrroowwss)). Similarly, β-AR-mediated changes in the cellular response of theactivated T-cell can indirectly affect APC response ((bbllaacckk aarrrroowwss)). BCR, B-cell receptor.



Bellinger DL, Lorton D. Autonomic regulation of cellular immune function. Auton Neurosci. 2014;182:15–41

38

AA.. Schematic showing the molecular mechanism (Sanders, 2012) through which β2-AR (R) signalingmodulates the production of IgG1 in an activated B-cell. Stimulation of β2-AR augments the rateof IgG1 transcription (e), synthesis and levels secreted by the B-cell (f).

SS influence on antibody production

Bellinger DL, Lorton D. Autonomic regulation of cellular immune function. Autonomic Neuroscience: Basic and Clinical, 2014David Vinyes, Sabadell (Barcelona) 2020


BB.. Schematic demonstrating the molecular mechanisms through which β2-AR signaling modulatesthe production of IgE in an activated B-cell. Stimulation of β2-AR creates a microenvironment thatpromotes IgE gene transcription (f) and greater synthesis (g) per B-cell.

β2-AR (R) Ligand (L) Norepinephrine


Dav

id V

inye

s, S

abad

ell (

Barc

elon

a) 2

020

The distal airway of the lung is innervated by vagus nerve. Upon stimulation, vagus nerveendings release acetylcholine or neuropeptides (NP) via C-fiber afferents to regulate lunginfection and immunity, coordinated with spleen.

Among the airway epithelial cells, pulmonary neuroendocrine cells are rare cellpopulation; however, these cells are innervated by sensory nerve endings and they couldsecrete NP that influence lung infection and immunity.

Huang Y, Zhao C, Su X. Neuroimmune regulation of lung infection and inflammation. QJM. 2019;112(7):483–487.

40

Cerebral compression causes SS vasoconstriction of the systemic and pulmonaryresistance and capacitance vessels. SS activation from the medullary vasomotor centeris the primary culprit leading to neurogenic pulmonary edema and hemorrhage. Vagalpathway plays minimal role.



Chen HI. Acute lung injury and acute respiratory distress syndrome: experimental and clinical investigations. J Geriatr Cardiol. 2011;8(1):44–54.

41

Dav

id V

inye

s, S

abad

ell (

Barc

elon

a) 2

020


Shanks J, Xia Z, Lisco SJ, et al. Sympatho-excitatory response to pulmonary chemosensitive spinal afferentactivation in anesthetized, vagotomized rats. Physiol Rep. 2018;6(12):e13742..

It is known that stimulation of vagal sensory fibers regulates rate and depth of breathing, basaltidal volume, cough and innervation of neuroepithelial bodies, but less is known aboutphysiological effects mediated by spinal SS afferent fibers.

It is seen that activation of the spinal sensory nerve fibers in the lung increases efferent SSnerve activity as evidenced by an increase in renal SS nerve activity, which likely mediates theincrease in heart rate and arterial pressure.

42David Vinyes, Sabadell (Barcelona) 2020


A pulmonary S-excitatory reflex that responds to noxious stimuli is identified, and it may haveimportant clinical implications. It is thought that most spinal SS fibers are often activated inconditions of inflammation and stress.

A link between inhaled activators of pulmonary sensory neurons and altered cardiacfunction has previously been described, for instance, those suffering from chronic obstructivepulmonary disease are more likely to have major adverse cardiovascular events .

A greater understanding of this pathway may contribute to the development of new therapeutic strategies.

A high vagal tone makes your body better at regulating blood glucose levels, reducing thelikelihood of diabetes, stroke and cardiovascular disease. Low vagal tone, has beenassociated with chronic IINNFFLL. (Rea WJ, Patel K. 2014. Reversibility of Chronic Degenerative Disease and Hypersensitivity. Vol. 1, FL:CRC Press)

IINNFFLL can damage organs and blood vessels if it persists when it is not needed. One of thevagus nerve's jobs is to reset the IISS and switch off production of proteins that fuel IINNFFLL. Lowvagal tone means this regulation is less effective and IINNFFLL can become excessive, such as inrheumatoid arthritis or in toxic shock syndrome. (Andersson, U., & Tracey, K. J. (2012). Neural reflexes in inflammationand immunity. The Journal of experimental medicine, 209(6), 1057–1068.)



Therapeutic proposal

44

SNA Balance

Local Anesthetic

Life History



Therapy with Local Anesthetics Neural Therapy

45

• Local anesthetic (LLAA) injections in low concentrations at specific NNSS points for therapeutic and diagnostic purposes.

• The points are specific depending on the LIFE HISTORY.

• The therapeutic purpose is REGULATORY.The main objective is to eliminate irritations of the NNSS, mainly the AANNSS, to recover its regulatory function.

(Barop H, 2017. Textbook and atlas of neural therapy: diagnosis and therapy with local anesthetics. Thieme ; Dosch P, DoschM., 2007. Manual of neural therapy according to Huneke. Thieme; Huneke F, 1989. Das Sekundenphänomen in derNeuraltherapie. Haug; Lorenz Fischer, 2019. Neuraltherapie. Neurophysiologie, Injektionstechnik und Therapievorschläge.Thieme ; Julio César Payán de la Roche, 2016. Desobediencia Vital. Instituto de Terapia Neural; ; Weinschenk, 2012. Neuraltherapy—A review of the therapeutic use of local anesthetics. Acupunct Relat Ther. 2012;1(1):5–9)



Neural Therapy What is Neural Therapy?

46

• SEGMENTAL (Barop 2017, Dosch 2007, Fischer 2019, Huneke 1989)

• INTERFERENCE FIELDS: irritated areas that can cause or maintain disruption, pain or IINNFFLLbeyond its segment. (Bahekar, Barop, Breebaart, Cornelissen, Dosch, Fischer, Huneke, Payán, Speransky)

• Somatization points of the emotions. (Vinyes D. 2020. Neural Therapy in anxiety. Neural Therapy International Congress. North American Academy of Neural Therapy)

NNTT uses the regulatory mechanisms and the plastic properties of the NNSSprimarily at this levels: Lorenz Fischer, 2014


Neural Therapy


• Some studies have shown that stellate ganglion block (SGB) can regulate multiplesystem functions in the body, and has good effect on blood pressure,hyperthyroidism, peripheral facial paralysis and other diseases (Joeng ES, 2016; Kim GW, 2016;Ghai A, 2016; Nie Y, 2016; Hanling SR, 2016).

• SSGGBB technique also plays an important role in regulating the IISS (Lypov E, 2015; Imani F,2016; Xavier TV, 2016; Singh Rana SP, 2015; Bataille B, 2016).

Stellate ganglion and regulation of IS


Neural Therapy


Colonoscopy scores of patients in the two groups.(a) P < 0.05 vs the control group before treatment. (c) P < 0.05 vs the control group after treatment.

Interactive contour map of time points and group factors.120 randomly selected patients with CUC. Control group (n=30): sulfasalazine. Experimental group (n=90): SGB (lidocaine, 1/dx30).


Local Anesthetic

Dav

id V

inye

s, S

abad

ell (

Barc

elon

a) 2

020

SGB reduces the production of INFLY cytokines in vivo in patients with chronic ulcerative colitis (CUC), and improves clinical symptoms

Lipov E, Candido K.. Efficacy and safety of stellate ganglion block in chronic ulcerative colitis. World J Gastroenterol. 2017


Local Anesthetic


SSGGBB is a clinical sympathetic block which can inhibit the body systemic IINNFFLLYY response.

It is seen than SSGGBB attenuates the sepsis-induced acute lung injury in rats, whichrepresents a novel treatment for sepsis.

Chen Y, Guo L, Lang H, et al. Effect of a Stellate Ganglion Block on Acute Lung Injury in Septic Rats. Inflammation. 2018;41(5):1601–1609.


Local Anesthetic

Dav

id V

inye

s, S

abad

ell (

Barc

elon

a) 2

020

Sphenopalatine Ganglion (SPG) Block might be an effective, safe and easy therapeutic option of Blood Pressure decrease in those hypertensive patients

with an activated SS Nervous System.

SSPPGG is connected with the brain stem and the Central NS through SS nerves derived mainlyfrom the Superior Cervical SS Ganglion and preganglionic PPSS nerves of the Facial nerve.

Triantafyllidi H, Arvaniti C, Palaiodimos L, et al. Infiltration of the sphenopalatine ganglion decreases blood pressure in newlydiagnosed and never treated patients with essential hypertension. Int J Cardiol. 2016;223:345–351

• reducing indirectly long-term potentiation in the SS ganglia• decreasing SS sprouting• decreasing SS-afferent coupling• decreasing the sympathetically mediated activity of WDR neurons• releasing pro- IINNFFLLYY neuropeptides from SS fibers• vasomotor-related IINNFF• disruption of the interaction between SS NNSS and IISS• temporarily disrupting the positive neuronal feedback loops (“reset”) and subsequently re-

organizing the systems involved

LLAA are gaining ground in the treatment of disorders of AANNSS disorders

Longstanding action of LLAA, mechanisms beyond pharmacological effect:


Dav

id V

inye

s, S

abad

ell (

Barc

elon

a) 2

020

Xie, 2007J Neurophysiol. ;97(1):492–502

Puente de la Vega Costa K et al.. Effects on hemodynamic variables and echocardiographic parameters after a stellateganglion block in 15 healthy volunteers. Auton Neurosci. 2016;197:46–55

LLAA have an inhibitory effect on the axonal transport of molecules involved in IINNFFLL, such as TNF-a.

The antioxidant properties of LLAA reduce oxidative stress (such as lipid peroxidation) involved inthe amplification of the IINNFFLL response and the production of pro-IINNFFLL cytokines.

The anti-IINNFFLL and anti-thrombotic effects of LLAA could be explained by the specific inhibition ofGq proteins and can do it in concentrations lower than those required to inhibit Na + channels.



Local Anesthetic

Cassuto J, Sinclair R, Bonderovic M. Anti-inflammatory properties of local anesthetics and their present and potential clinical implications. Acta Anaesthesiol Scand. 2006;50(3):265–282

LA have been shown to be potent inhibitors of INFL-induced edema formation in variousconditions, like lung injury, myocardial ischemia, obstructed gut induced, burned skin,septic shock.

Accumulated data clearly shows that the LA have antibacterial, antiviral and antifungaleffects.

Substantial evidence has accumulated to support the broad aannttii--IINNFFLLYY properties of LLAA, which in some cases may exceed in potency the actions of traditional steroids and NSAID with fewer adverse effects.



Local Anesthetic

Cassuto J, Sinclair R, Bonderovic M. Anti-inflammatory properties of local anesthetics and their present and potential clinical implications. Acta Anaesthesiol Scand. 2006;50(3):265–282

Smaller concentration of LLAA compared to the ones used clinically may maintain ananti-INFLY and, therefore, analgesic effect without the risk of possible toxicity.



Local Anesthetic

Pietruck C, Grond S, Xie GX, Palmer PP. Local anesthetics differentially inhibit sympathetic neuron-mediated and C fiber-mediatedsynovial neurogenic plasma extravasation. Anesth Analg. 2003;96(5):

Inhibition of hyperalgesia and local IINNFFLL by a nerve block is associated with inhibition ofincreased COX-2 expression in bone marrow and spinal ganglia, and also inhibits secondaryPGE2 production in CSF.Systemic bupivacaine did not alter COX-2 expression.



Local Anesthetic

Beloeil H, Mazoit JX. Effet des anesthésiques locaux sur la réponse inflammatoire postopératoire [Effect of local anestheticson the postoperative inflammatory response]. Ann Fr Anesth Reanim. 2009;28(3):231–237.

56

• Few of side affects• Low half life period• Low toxicity• Local Anesthesia• Sympathicolytic• Vascular dilatation• Anti-inflammatory• Anti-rheumatic

• Broncho-spasmolytic• Increase of coronary perfusion• Negative inotrope• Anti-arrhythmic• Anti-microbial• Anti-cancerous

Reuter UR, Oettmaier R, Nazlikul H (2017).Procaine and Procaine-Base-Infusion: a Review of theSafety and Fields of Application after 20 years of use.Clin Res Open Access 4(1)


Neural Therapy


ProcainePharmacological and clinical properties


Neural Therapy

Dav

id V

inye

s, S

abad

ell (

Barc

elon

a) 2

020

Aim: to observe the effect of verapamil-procaine compound (V-P) on prevention andtreatment of acute respiratory distress syndrome (ARDS) subsequent to high riskoperation.

Significant difference was found between control and V-P or procaine group (both P<0.01),but no significant between procaine and V-P groups.

The V-P can interrupt Inflammatory Response Syndrome to develop Acute Lung Injury,then Respiratory Distress Syndrome (ARDS) and Multiple Organ Dysfunction Syndrome,and thus prevents and cures ARDS.

Shi JY, Li JZ, Wang WG, et al. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue. 2005;17(6):357–360


Neural Therapy


The acute respiratory distress syndrome (ARDS) remains a world-wide treatmentchallenge, with high morbidity and mortality. The central pathophysiology of ARDScenters around IINNFFLL in the lung and increased microvascular permeability.

LLAA have been shown to attenuate the IINNFFLL in lung and in ARDS.

Krishnamoorthy, V., & Chung, L. (2014). Bench-to-bedside: The use of local anesthetics to attenuate inflammationin acute respiratory distress syndrome. International journal of critical illness and injury science, 4(2), 98–100.


• Discomforts description(where, since when, what do they associate it with…)

• Childhood ailments (especially infections)• Unique or recurring infections• Gynecological history (deliveries, abortions, periods)• Surgeries• Other scars• Injuries of any other kind (even during delivery)

• DENTAL Records

Life History An important tool


Dav

id V

inye

s, S

abad

ell (

Barc

elon

a) 2

020


Life History

Case reports published by several authors suggest that interference fields (such as scars) and their distant adverse effects can be temporarily or lengthily eliminated by injection of LLAA..

Barop, 2017; Barbagli P, 2009. Clin Ter 160(6):445–9; Brobyn TL, 2015. J Pain Reli 04(03):1–4 ; Chung MK, 2017. Holist Nurs Pract 31(1):21-29; Dosch, 2007; Fischer, 2019; Huneke, 1989; Payán, 2016; Weinschenk, 2012

Bree

baar

tAC,

Bijl

sma

JW, v

an E

den

W. 1

6-ye

ar re

miss

ion

of

rheu

mat

oid

arth

ritis

afte

runu

sual

lyvi

goro

ustr

eatm

ento

f cl

osed

dent

al fo

ci. C

linEx

pRh

eum

atol

. 200

2;20

(4):5

55–5

57.

• Retrospective randomly selected study with1000 patients (2016) showed a significantassociation between oral health and generalhealth,

• and confirmed a correlation between dentalinfections and medical disorders.

• The diagnosis of oral disease was basedprimarily on radiographic findings.


Life History


Joseph, B.K., Kullman, L. & Sharma, P.N. The oral-systemic disease connection: a retrospective study. Clin Oral Invest 2200,, 2267–2273 (2016).


Life History


They claim that the dental health and the health of the rest of the body are notseparated, since they are integrally interconnected by the complete configurationand health of the person. https://www.nidcr.nih.gov/


Neural Therapy

Dav

id V

inye

s, S

abad

ell (

Barc

elon

a) 2

020 Treatments with LLAA, known as NNTT, can be done quickly, on an

outpatient basis and with minimal side effects, and that it canlead to a reduction in drug use.

Repeated injections of LLAA can lead to extinction of storedpathological irritation of SS NNSS and restoration of normal tissueperfusion, (Lorenz Fischer, 2019. Neuraltherapie. Georg Thieme Verlag KG)

Advantages

and along with this, to what the Colombian physician JJCC PPaayyáánn ddee llaa RRoocchhee defines as:

the self-eco-organization of the LIVE BEING

Julio César Payán de la Roche, 2016. Desobediencia Vital. Avaiable from www.terapianeural.com

DDaavviidd VViinnyyeess, MD · Sabadell (Barcelona)[email protected] · @david.vinyes

International Federation of Medical Associations of Neural Therapy

Member of Scientific and Ethics CommissionInternational RepresentativePresidentMedical Director Director of Master Degree in Neural Therapy and Neurofocal Dentistry

AAuuttoonnoommiicc NNeerrvvoouuss SSyysstteemm

IImmmmuunnee SSyysstteemm

IInnffllaammmmaattiioonn

aanndd LLooccaall AAnneesstthheettiiccss

NNeeuurraall TThheerraappyy aass aa ttrreeaattmmeenntt ooppttiioonn

Documents

Autonomic Nervous System (ANS) Immune System (IS ...Autonomic NS, Immune S, Inflammation and Local Anesthetics. Neural Therapy as a treatment option Neural Therapy David Vinyes, Sabadell