Neuroimmune Mechanisms of the Subluxation Complex

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MSCA D-II December 2011 Seminar

Andrew S. Bonci, BA, DC

DisclosuresI stand before you with no conflicts of interest. I make my living the way you do, by lightening the burden of human suffering with chiropractic.ci . Bon wS ndre ractor Dr. A irop Ch

I have nothing to sell to you, so relax and enjoy yourself and your time with your peers.www.drbonci.com

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DedicationGalileo Galilei(1564 1642) Father of Modern Science In spite of being found "vehemently suspect of heresy" by the medieval Church for his theory of heliocentrism, he held fast to the belief that science and philosophy were compatible and very necessary bed partners.www.drbonci.com

Special Thank You MSCA-DII

Dr. Ron Manfredi

Dr. Robert Riley

Dr. Russell Matthias

Dr. Doran Nicholson

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My Take Home Message

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Disce Aut Discedewww.drbonci.com

Seminar ObjectivesWe will explore the pertinent evidence in the peer-reviewed literature and integrate the following:1. The neuroscience underlying neurogenic inflammation, antidromic vasodilation, tachykinin release and pathophysiologic end-organ changes. 2. The immunology underlying neuronal monoamine oxidation, lymph node denervation and loss of immune competence. 3. The neuroimmune characteristics of connective tissue and its influence on nerve function. 4. Contextualize these understandings into the philosophy, art and science of chiropractic and nutritional recommendations.www.drbonci.com

James Firth, DC, PhC"You do not know enough the moment you believe your education is over. You cannot teach after you stop learning. No allegiance is paid to inefficiency. No matter who you are or what you do ... doctor, lawyer or merchant your guidance will be deserted, your counsel avoided and your wares rejected in the face of better brains or brands."James Firth, DC Chiropractic Symptomatology. 1914 www.drbonci.com

The ChallengePatient has acid stomach. Patient takes Pepcid (famotidine). After adjusting T6 he no longer needs Pepcid. It would be nice if you could explain that one.

If it's true that these work,

then it should follow that ... there is some overlapping mechanism of action that can be identified. a review of the pharmacological mechanisms of action of Pepcid can help in our understanding of chiropractic.

deductive reasoning can serve as our methodology in this pursuit.

Nobody's selling out to the Pharmocracy.

Dr. Bonci, Please!

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Art. 19:

THE THREE PHASES OF CHIROPRACTIC STUDY1. Study of the Immaterial. 2. Study of the Material. 3. Study of Art.Stephenson RW. Chiropractic Text Book. Freshman Text. 1927.

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Study of the ImmaterialThe study of the Immaterial is the study of philosophy; that is to say, the study of intelligence, laws, causes, effects, rules, theories, functions and other abstractions. It is to gain a knowledge of the group of principles underlying the science.Stephenson RW. Chiropractic Text Book. Freshman Text. 1927. www.drbonci.com

Video

Dr. Edward Atkinson in his Antarctica lab www.drbonci.com circa 1910.

Art. 19:

THE THREE PHASES OF CHIROPRACTIC STUDY1. Study of the Immaterial. 2. Study of the Material. 3. Study of Art.Stephenson RW. Chiropractic Text Book. Freshman Text. 1927.

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Study of the MaterialIn order that the chiropractor know something about the material and structure of the body, it is advisable for him to study the materials in order to understand the actions of structures in function; to better understand the effects of causes, and to trace to causes from the effects.Stephenson RW. Chiropractic Text Book Freshman Text. 1927. www.drbonci.com

The ChallengePatient has acid stomach. Patient takes Pepcid (famotidine). After adjusting T6 he no longer needs Pepcid. It would be nice if you could explain that one.

If it's true that these work,

then it should follow that ... there is some overlapping mechanism of action that can be identified. a review of the pharmacological mechanisms of action of Pepcid can help in our understanding of chiropractic.

deductive reasoning can serve as our methodology in this pursuit.

What is Pepcid?Pepcid is in a group of drugs called histamine2 blockers. It works by decreasing the amount of acid produced by the parietal cells of the stomach.http://www.drugs.com/pepcid.html www.drbonci.com

What is the Source of the Histamine?Enterochromaffin-like cells or ECL cells are a type of neuroendocrine cells found in the gastric glands of the gastric mucosa beneath the epithelium, in particular in the vicinity of parietal cells.http://en.wikipedia.org/wiki/ECL_cell www.drbonci.com

What is the Relationship of Parietal and ECL Cells?

In Practice 2010;32:478-483 doi:10.1136/inp.c6670

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An ECL Cell is a TMC

Tissue Mast Cell

Enterochromaffin-like Cellwww.drbonci.com

What are the Neural Connections to the Parietal Cell?Acetylcholine

PARIETAL cellACh receptor

Ach or acetylcholine is the neurotransmitter of the postganglionic parasympathetic fibers.HCl secretion

These fibers derive through the Vagus Nerve (CN X)www.drbonci.com

What are the Autonomic Connections to the Enterochromaffin-like Cell?AcetylcholineACh receptor

Vagal motor fibers synapse to the Enterochromaffin-like cells and Parietal cells.PARIETAL cell HCl secretion

ECL cellhistaminesecreting cell

histamine receptor

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Autonomic System ReviewParasympathetic

Sympathetic

Preganglionic Cholinergic System Postganglionic Cholinergic System

Preganglionic Cholinergic System Postganglionic Adrenergic System (predominantly)

The Autonomic System is defined based on its motor function. It is visceromotor ONLY. Its function is derived from the postganglionic neurotransmitter/end-organ interaction.www.drbonci.com

Subluxation Induced Vagal Irritation ... could result in postganglionic, cholinergic stimulation of the parietal cell. could result in postganglionic, cholinergic stimulation of enterochromaffin like cell.www.drbonci.com

But, the Patient Improved with a Thoracic Adjustment ...AcetylcholineACh receptor

NE or norepinephrine is the neurotransmitter of the postganglionic sympathetic fibers.PARIETAL cell HCl secretion

ECL cellhistaminesecreting cell

histamine receptor

These fibers are derived through the Celiac Plexus.www.drbonci.com

Splanchnic & Cranial NervesAutonomic motor fibers travel through peripheral nerves called splanchnic and cranial nerves to innervate internal organs. These peripheral nerves also convey sensory fibers.www.drbonci.com

Dr. Bonci, Please!

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What was I Missing?There are no noradrenergic (sympathetic) inputs to the parietal cells nor to the enterochromaffin-like cells. What could be the role of the thoracic adjustment in normalizing stomach acid?www.drbonci.com

Neurokinin ReceptorsAcetylcholine TachykininACh receptor

ECL cellhistaminesecreting cell

PARIETAL cell HCl secretion

Neurokinin Receptor

histamine receptor

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Neurohormonal Modulation of Rat Enterochromaffin-like Cell Histamine Secretion.Gastric mucosal cells and nerve terminals contain ... substance P ... These data are consistent with the hypothesis that substantial neurohormonal modulation of ECL cell function exists.Sandor A, et. al. Gastroenterology. 1996 Apr;110(4):1084-92.

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Sensory-Effector InnervationEnterochromaffin-like Cells /Tissue Mast Cells receive sensory c-fiber innervation. Sensory fibers have an effector function with the release of a a class of neurotransmitters known as tachykinins.www.drbonci.com

Sensory-Effector TriggerSensory fibers can play a nontraditional motor function. In this case, sensory fibers carried by the splanchnic nerves can indirectly trigger the release of protons from the parietal cells. This is a significant piece of the chiropractic puzzle.

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Neurogenic InflammationThe role of sensory nerves and axon reflexes in producing inflammation was recognized in the early 1900s. Nevertheless, neurogenic inflammation captured the interest of the international scientific community only during the 1980s.

Neurogenic inflammation CRC press; 1996: page 33

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On the origin from the spinal cord of the vaso-dilator fibres of the hindlimb, and on the nature of these fibres.Bayliss WM. J Physiol. 1901 Feb 28;26(34):173-209.www.drbonci.com

Further researches on antidromic nerve-impulses.Bayliss WM. J Physiol. 1902 Jul 21;28(4):27699.www.drbonci.com

The Science of ChiropracticDD Palmer 1906; p. 36

Looking over our immense vertebral collection [] we find caries limited, as a rule, to the bodies and articular processes. The laminae, transverse and spinous processes are rarely affected. Various reasons have been assigned by various authors [] until I discovered that heat was produced by nerves. Excessive heat softens bone, producing caries. Articular and intervertebral cartilages become fibrillated, disintegrated, and the adjacent parts of the bodies affected by caries.www.drbonci.com

Triple Response of Lewis1.Red reaction-red line(transient local vasodilation due to histamine) 2.Flare-spreading redness extending beyond the red line(due to axon reflex) 3.Wheal-Swelling/localized edema in the region of the redline(increased capillary permeability due to histamine)Sir Thomas Lewis Circa 1927

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Nerve Irritation circa 1910Nerve irritation creates heat by increasing molecular vibration. An excess of heat disturbs circulation, innervation and the cellular process of metabolism.DD Palmer. Chiropractor's Adjuster. 1910; page 26.

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Uninhibited reversible antidromic vasodilation in pathophysiologic diseases: Arteriosclerosis, carcinogenesis, neuritis, and osteoporosis.Hackett GS. Angiology. 1966 Feb;17(2):109-18.www.drbonci.com

Antidromic vasodilatation and neurogenic inflammation.Szolcsnyi J. Agents Actions. 1988 Feb;23(1-2):4-11.www.drbonci.com

Antidromic Vasodilatation and Neurogenic Inflammation.Antidromic stimulation of the lumbosacral dorsal roots of the rat

evokes a long-lasting increase in cutaneous microcirculation of the paw and induces plasma extravasation in the innervated skin areas and various pelvic organs.

This local neuroregulatory mechanism mediates neurogenic inflammation, cutaneous vasodilatation ...Szolcsnyi J. Agents Actions. 1988 Feb;23(1-2):4-11. www.drbonci.com

Sensory Nerve-Mast Cell Communication

Saban R et al. Am J Physiol Renal Physiol 2002;283:F616-F629

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Obscured from ViewIn the 1970s one can find no references to neurogenic inflammation or its synonyms among the subject indexes of published works on inflammatory processes.Neurogenic inflammation CRC press; 1996: page 33www.drbonci.com

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Neurogenic Inflammation Summary

#1: Sensory-Effector FacilitationEnd-Organ Changes

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Nociceptive Threshold[I]njection of PGE2 at the sight of receptor terminals fails to evoke any response in the fiber, yet the nociceptive threshold to mechanical and chemical stimuli is decreased.Pitchford S., Levine JD. Prostaglandins sensitize nociceptors in cell culture. Neuroscience letters 1991; 132:105-108.

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Neurogenic Inflammation Summary

#2: Antidromic Release Of TachykininsEnd-Organ Changes

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Neurogenic Inflammation Emergence and the Sensory-Effector SystemRelease of Substance -P & other tachykinins from free nerve Ending.Antidromic

To The CNS

Orthodromic

Orthodromic

"Axon Reflex" The orthodromic impulse is "reflexively" converted into an antidromic impulse at the level of the axon. This is accomplished without spinal cord assistance.

Nociceptive, Orthodromic Input

DRG Irritation results in both orthodromic AND antidromic impulse propagation.

Tissue Mast Cell Stimulation with resultant release of histamine, heparin and proteases.

Neurogenic Inflammation Summary

#3: Mast Cell DegranulationEnd-Organ Changes

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Sensory Nerve-Mast Cell RelationshipJ Dermatol Sci. 2006 Apr;42(1):47-54.

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Neurogenic Inflammation Summary

#4: Immune Cell Infiltration: Neutrophils & MacrophagesRobbins Patologa Humana ed 8: Captulo 2: Inflamacin Aguda y Crnica. (2008; pp 33-61) End-Organ Changes

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Neurogenic Inflammation Summary

#5: End-Organ TransformationRobbins Patologa Humana ed 8: Captulo 3: Reparacin Tisular: Regeneracin, Curacin y Fibrosis. (2008; pp 63-84) End-Organ Changes

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Mechanisms of End-Organ Transformation

Tissue Injury Toxic Oxygen Metabolites Proteases Neurtophil Chemotactic Factors CoagulationFactors Arachidonic Acid Metabolites Nitric Oxide

Fibrosis Growth Factors (PDGF, FGF, TGF-B) Fibrogenic Cytokines Angiogenesis Factors (FGF) "Remodeling" Collagenases

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http://www.robbinspathology.com/

Article 134:

Accumulative Destructive Survival Value

It is the result of unsuccessful adaptation; has to do with destruction or depletion.Stephenson RW. Chiropractic Text Book. Sophmore Text. 1927.

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Dr. Bonci, Please!

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