Neuroimmune Mechanisms 1 | Autonomic Nervous System | Acetylcholine

Neuroimmune

Mechanisms of
the Subluxation
Complex

Andrew S. Bonci, BA, DC

www.drbonci.com

MSCA D-II December 2011 Seminar

Disclosures
I 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.
nci
o
B
.
ew S tor
r
d
n
Dr. A iroprac
Ch

I have nothing to sell to
you, so relax and enjoy
yourself and your time with
your peers.
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2

Dedication
Galileo 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.
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Special Thank You … MSCA-DII

Dr. Ron Manfredi

Dr. Robert Riley

Dr. Russell Matthias

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Dr. Doran Nicholson

4

My Take
Home Message

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Disce
Aut
Discede
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Seminar Objectives
We 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.
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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
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The Challenge
Patient 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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THE THREE PHASES OF
CHIROPRACTIC STUDY

Art. 19:

1. 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 Immaterial
The 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.
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Video

Dr. Edward Atkinson in his Antarctica labwww.drbonci.com
circa 1910.

THE THREE PHASES OF
CHIROPRACTIC STUDY

Art. 19:

1. 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 Material
In 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.
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The Challenge
Patient 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

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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
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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 Cell
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What are the Neural Connections
to the Parietal Cell?
Acetylcholine

PARIETAL cell
ACh
receptor

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

These fibers derive
through the Vagus
Nerve (CN X)
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What are the Autonomic Connections
to the Enterochromaffin-like Cell?
Acetylcholine
ACh
receptor

ECL cell

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

histaminesecreting cell

HCl
secretion

histamine
receptor

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Autonomic System Review
Parasympathetic

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.
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Subluxation Induced
Vagal Irritation ...
… could result in
postganglionic,
cholinergic stimulation
of the parietal cell.
… could result in
postganglionic,
cholinergic stimulation
of enterochromaffin like
cell.
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But, the Patient Improved with a
Thoracic Adjustment ...
Acetylcholine
ACh
receptor

ECL cell

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

histaminesecreting cell

HCl
secretion

histamine
receptor

These fibers are derived through
the Celiac Plexus.
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Splanchnic & Cranial Nerves
Autonomic motor fibers
travel through
peripheral nerves
called splanchnic and
cranial nerves to
innervate internal
organs.
These peripheral nerves
also convey sensory
fibers.
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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?
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Neurokinin Receptors
Acetylcholine
ACh
receptor

Tachykinin

PARIETAL cell

ECL cell
histaminesecreting 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 Innervation
Enterochromaffin-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.
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Sensory-Effector Trigger
Sensory 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 Inflammation
The 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.
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Further
researches on
antidromic
nerve-impulses.
Bayliss WM. J Physiol.
1902 Jul 21;28(4):27699.
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The Science of Chiropractic
DD 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.
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Triple Response of Lewis
1.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)

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Sir Thomas Lewis
Circa 1927

Nerve Irritation circa 1910
“Nerve 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.
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Antidromic
vasodilatation
and neurogenic
inflammation.
Szolcsányi J. Agents
Actions. 1988
Feb;23(1-2):4-11.
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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 ...
Szolcsányi J. Agents Actions. 1988 Feb;23(1-2):4-11.

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Sensory Nerve-Mast Cell
Communication

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

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Obscured from View
In 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 33
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Neurogenic Inflammation Summary

#1:
Sensory-Effector Facilitation
End-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 Tachykinins
End-Organ
Changes

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Neurogenic Inflammation Emergence
and the Sensory-Effector System
Release 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.

DRG Irritation results in
both orthodromic AND
antidromic impulse propagation.

Nociceptive,
Orthodromic
Input

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

Neurogenic Inflammation Summary

#3:
Mast Cell Degranulation
End-Organ
Changes

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

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Neurogenic Inflammation Summary

#4:
Immune Cell Infiltration:
Neutrophils & Macrophages
Robbins Patología Humana ed 8:
Capítulo 2: Inflamación Aguda y Crónica.
(2008; pp 33-61)

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End-Organ
Changes

Neurogenic Inflammation Summary

#5:
End-Organ Transformation
Robbins Patología Humana ed 8:
Capítulo 3: Reparación Tisular: Regeneración, Curación 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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