Download Scientific Basis of Pain

Scientific Basic of Pain
RM Clemmons, DVM, PhD, CVA. CVFT
University of Florida
PAIN
• Unpleasant sensory and emotional
experience associated with actual or
potential tissue damage
• Functions: Stop Signal
• Warning of a threat
• Basis of learning
• Forces a person to rest
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Terminology
• Noxious – harmful, injurious
•
Noxious stimuli – stimuli that
activate nociceptors
(pressure, cold/heat extremes,
chemicals)
• Nociceptor – nerve receptors
that transmits pain impulses
• Pain Threshold – level of
noxious stimulus required to
alert an individual of a
potential threat to tissue
• Pain Tolerance – amount of
pain a person is willing or able
to tolerate
• Hyperesthesia – abnormal
acuteness of sensitivity to
touch, pain, or other sensory
stimuli
• Paresthesia – abnormal
sensation, such as burning,
pricking, tingling
• Analgesic – a neurologic or
pharmacologic state in which
painful stimuli are no longer
painful
Overview of Neural Integration
Figure 15.1
Neural pathways
• Afferent pathways
• Sensory information coming from the
sensory receptors through peripheral nerves
to the spinal cord and on to the brain
• Efferent pathways
• Motor commands coming from the brain and
spinal cord, through peripheral nerves to
effecter organs
Types of Nerves
• Afferent (Ascending) – transmit impulses
from the periphery to the brain
• First Order neuron
• Second Order neuron
• Third Order neuron
• Efferent (Descending) – transmit impulses
from the brain to the periphery
Sensory receptor
• Specialized cell or cell process that
monitors specific conditions
• Arriving information is a sensation
• Awareness of a sensation is a perception
Senses
• General senses
•
•
•
•
Pain
Temperature
Physical distortion
Chemical detection
• Receptors for general senses scattered throughout the
body
• Special senses
• Located in specific sense organs
• Structurally complex
Sensory receptors
• Each receptor cell monitors a specific
receptive field
• Transduction
• A large enough stimulus changes the
receptor potential, reaching generator
potential
Figure 15.2
Three types of nociceptor
• Provide information on pain as related to
extremes of temperature
• Provide information on pain as related to
extremes of mechanical damage
• Provide information on pain as related to
extremes of dissolved chemicals
• Myelinated type A fibers carry fast pain
• Slower type C fibers carry slow pain
Thermoceptors and
mechaniceptors
• Found in the dermis
• Mechaniceptors
• Sensitive to distortion of their membrane
• Tactile receptors (six types)
• Baroreceptors
• Proprioceptors (three groups)
Skin Tactile Receptors
Figure 15.3a-f
Sensory Receptors
• Mechanoreceptors – touch, light or deep
pressure
• Meissner’s corpuscles (light touch), Pacinian
corpuscles (deep pressure), Merkel’s corpuscles (deep
pressure)
• Thermoreceptors - heat, cold
• Krause’s end bulbs ( temp & touch), Ruffini corpuscles
(in the skin) – touch, tension, heat; (in joint capsules &
ligaments – change of position)
• Proprioceptors – change in length or tension
• Muscle Spindles, Golgi Tendon Organs
• Nociceptors – painful stimuli
• mechanosensitive
• chemosensitive
Nerve Endings
• “A nerve ending is the termination of a nerve fiber
in a peripheral structure.”
• Nerve endings may be sensory (receptor) or
motor (effector).
• Nerve endings may:
• Respond to phasic activity - produce an impulse when
the stimulus is  or , but not during sustained
stimulus; adapt to a constant stimulus (Meissner’s corpuscles &
Pacinian corpuscles)
• Respond to tonic receptors produce impulses as long
as the stimulus is present. (muscle spindles, free n. endings,
Krause’s end bulbs)
Nerve Endings
•
Merkel’s corpuscles/disks •
•
•
•
•
•
•
Sensitive to light touch &
vibrations
Rapid adapting
Superficial location
Pacinian corpuscles •
•
•
Sensitive to deep pressure &
vibrations
Rapid adapting
Deep subcutaneous tissue
location
Krause’s end bulbs –
•
•
•
Thermoreceptor
Ruffini corpuscles/endings
•
•
•
Meissner’s corpuscles –
•
•
Sensitive to touch & vibration
Slow adapting
Superficial location
Most sensitive
•
Thermoreceptor
Sensitive to touch & tension
Slow adapting
Free nerve endings •
•
Afferent
Detects pain, touch,
temperature, mechanical
stimuli
Nociceptors
• Sensitive to repeated or prolonged stimulation
• Mechanosensitive – excited by stress & tissue
damage
• Chemosensitive – excited by the release of
chemical mediators
• Bradykinin, Histamine, Prostaglandins, Arachadonic
Acid
• Hyperalgesia
• Primary Hyperalgesia – due to injury
• Secondary Hyperalgesia – due to spreading of chemical
mediators
First Order Neurons
•
Stimulated by sensory receptors
•
End in the dorsal horn of the spinal cord
•
Types
• A-alpha – non-pain impulses
• A-beta – non-pain impulses
• Large, myelinated
• Low threshold mechanoreceptor; respond to light touch & lowintensity mechanical info
• A-delta – pain impulses due to mechanical pressure
• Large diameter, thinly myelinated
• Short duration, sharp, fast, bright, localized sensation (prickling,
stinging, burning)
• C – pain impulses due to chemicals or mechanical
• Small diameter, unmyelinated
• Delayed onset, diffuse nagging sensation (aching, throbbing)
Second Order Neurons
• Receive impulses from the FON in the dorsal
horn
• Lamina II, Substantia Gelatinosa (SG) - determines the
input sent to T cells from peripheral nerve
• T Cells (transmission cells): transmission cell that
connects sensory n. to CNS; neurons that organize
stimulus input & transmit stimulus to the brain
• Travel along the spinothalmic tract
• Pass through Reticular Formation
• Types
• Wide range specific
• Receive impulses from A-beta, A-delta, & C
• Nociceptive specific
• Receive impulses from A-delta & C
• Ends in thalamus
Third Order Neurons
• Begins in thalamus
• Ends in specific brain centers
(cerebral cortex)
• Perceive location, quality, intensity
• Allows to feel pain, integrate past
experiences & emotions and determine
reaction to stimulus
Descending Neurons
• Descending Pain Modulation (Descending Pain
Control Mechanism)
• Transmit impulses from the brain (corticospinal
tract in the cortex) to the spinal cord (lamina)
• Periaquaductal Gray Area (PGA) – release enkephalins
• Nucleus Raphe Magnus (NRM) – release serotonin
• The release of these neurotransmitters inhibit ascending
neurons
• Stimulation of the PGA in the midbrain & NRM in
the pons & medulla causes analgesia.
• Endogenous opioid peptides - endorphins &
enkephalins
Neurotransmitters
•
Chemical substances that allow nerve impulses to move from one
neuron to another
•
Found in synapses
•
Substance P
• thought to be responsible for the transmission of pain-producing impulses
•
Acetylcholine
• responsible for transmitting motor nerve impulses
•
Enkephalins
• reduces pain perception by bonding to pain receptor sites
•
Norepinephrine
• causes vasoconstriction
•
2 types of chemical neurotransmitters that mediate pain
• Endorphins
•
morphine-like neurohormone; thought to  pain threshold by binding to receptor sites
• Serotonin
•
substance that causes local vasodilation &  permeability of capillaries
• Both are generated by noxious stimuli, which activate the inhibition of pain
transmission
•
Can be either excitatory or inhibitory
Somatic Sensory Pathways
• Three major pathways carry sensory
information
• Posterior (Dorsal) column pathway
• Anterolateral pathway
• Spinocerebellar pathway
Ascending Tracts in the Spinal Cord
Figure 15.6
Posterior column pathway
• Carries fine touch, pressure and
proprioceptive sensations
• Axons ascend within the fasciculus
gracilis and fasciculus cuneatus
• Relay information to the thalamus via
the medial lemniscus
Dorsal Columns & Spinothalamic
Tracts
Figure 15.8a, b
Spinothalamic pathway
• Carries poorly localized sensations of touch,
pressure, pain, and temperature
• Axons decussate in the spinal cord and ascend
within the anterior and lateral spinothalamic
tracts
• Headed toward the ventral nuclei of the
thalamus
Role of Thalamus
• Second order neurons transmit pain and temperature
signals to thalamus contralateral to stimulated receptor
• VPM processes pain and temperature signals from
trigeminal (CNV) analog of spinothalamic system for head
and neck
• VPL processes pain and temperature signals from
peripheral regions of the body such as viscera, trunk and
limbs
• Medial (intralaminar) thalamic nuclei process pain and
temperature signals from reticular formation (spinoreticular
fibers) such as raphe nuclei and locus coruleus
• Central (thalamic) pain signals cannot be localized (e.g.,
metastatic cancer) and central (thalamic) pain syndrome is
relieved by producing electrical lesions in a thalamotomy
procedure
Role of Cerebral Cortex
• Pain and temperature signals transmitted from VPL and
VPM (specific thalamic nuclei) to somatosensory cortices SI
and SII for localization
• Pain and temperature signals transmitted from medial
intralaminar (nonspecific) nuclei to all regions of cerebral
cortex for “alerting” response, which induce wakefulness
and inhibit sleep
• Pain and temperature signals also transmitted from
intralaminar nonspecific nuclei to limbic system,
hypothalamus and associated structures for emotional,
endocrine, stress and autonomic responses which produce
fear, suffering, cardiovascular, respiratory, gastrointestinal,
urogenital and stress-related hormonal responses
Where Does Pain Come From?
• Cutaneous Pain
• sharp, bright, burning; can have a fast or slow onset
• Deep Somatic Pain
• stems from tendons, muscles, joints, periosteum, & b.
vessels
• Visceral Pain
• originates from internal organs; diffused @ 1st & later
may be localized (i.e. appendicitis)
• Psychogenic Pain
• individual feels pain but cause is emotional rather than
physical
Types of Pain: Classification by
Duration Acute vs chronic
1
Acute pain
Chronic pain
•An unpleasant experience with
emotional, cognitive, and
sensory features, resulting from
tissue trauma
•
• Usually associated with
significant, observable tissue
pathology
•
• Resolves with healing of
causative injury
• Protective biological function to
protect against further injury;
protective reflexes include
withdrawal, muscle spasm, and
autonomic reactions
•
Pain lasting beyond
expected recovery period
and identifiable pathology
insufficient to explain the
pain state
Disrupts sleep and normal
activities of living
Does not serve a protective,
adaptive function
Types of Pain: Classification by
Etiology Nociceptive vs neuropathic
1
Nociceptive pain
Neuropathic pain
• Results from normal function of
the nervous system
•
• Caused when a noxious
stimulus (eg, trauma,
inflammation, infection)
activates A-delta and C
nociceptors
•
— Visceral pain: originates in
internal organs
— Somatic pain: originates in
skin, muscle, skeletal
structures
•
Abnormal nociceptive signaling
caused by an impairment of the
nervous system
Serves no functional or adaptive
purpose
Causes and examples
—
Metabolic: diabetic neuropathy
—
Infectious: herpes zoster
—
Trauma: nerve entrapment
The Neurophysiology of Pain
• Nociception: process by which information about tissue
damage reaches the central nervous system
• Transduction
• Transmission
•
Perception
•
Modulation
Pain Transduction
• Nociceptor = pain receptor: specialized receptor for detecting
tissue injury/damage
• Two classes of nociceptive afferent fibers
A-delta axon
C axon
A-delta
C
Caliber
Small diameter,
thinly myelinated
Small diameter,
unmyelinated
Stimuli
Thermal & high-threshold
mechanical
Polymodal: high-intensity
mechanical, chemical,
heat, cold
5-30
0.5-2
Short, sharp, prickling pain
More prolonged sensation
of dull pain
Type
Conduction
velocity
(meters/sec)
Effect of
activation
Pain Transduction
• Nociceptors do not spontaneously depolarize:
they send impulses (action potentials) only when
stimulated
• No specialized pain “receptors”
• The receptor region of the nociceptor is the free terminal
of the axon
• Ion channels in nerve terminal open in response
to noxious stimuli, initiating an action potential, the
“pain signal”
• Peripheral sensitization: local tissue injury with
release of inflammatory mediators can enhance
nociceptor response
Small Diameter Afferent Fibers
• Cutaneous mechanoreceptors
• Respond to nondiscriminative tactile
stimuli
• Pinch, rub, stretch, squeeze
• A-delta and C fiber, high-threshold
• Cutaneous thermoreceptors
• Respond to transient change in
temperature
• Innocuous ward and cool stimuli
Small Diameter Afferent Fibers
• Cutaneous nociceptors – cutaneous pain
• A-delta mechanoreceptors
• Mechanical tissue damage
• C-polymodal nociceptors
• Mechanical tissue damage, noxious thermal stimuli, endogenous
algesic chemicals
• C-fiber mechanonociceptors
• A-delta heat thermonociceptors
• A-delta, C-fiber cold thermonociceptors
• C-fiber chemonociceptors – algesic chemicals
Pain Transmission
• Nociceptors (primary sensory afferents) have cell body in
dorsal root ganglia; synapse to second-order neurons in
dorsal horn of spinal cord
• Pain impulses can trigger a withdrawal reflex via
connections to motor neurons in the spinal cord
• Impulses ascend to brain via various ascending tracts
CNS Neurotransmitters of A-delta
and C-fibers
• Substance P (Neuropeptide)
• Calcitonin Gene Related Peptide
(CGRP)
• Excitatory amino acids – e.g., glutamate
• Release in ischemia/hypoxia - neurotoxicity
Pain Perception
• Perception of and reaction to pain are influenced by social
and environmental cues, as well as by cultural norms and
personal experience
• Both cortical and limbic systems are involved in conscious
awareness (perception) of pain
• Recognition of location, intensity, and quality of pain is
mediated by processing of signals from the spinothalamic
tract > thalamus > somatosensory cortex
• Pain information processing in the brainstem, midbrain,
and limbic system appear to mediate affective, motivational,
and behavioral responses to painful stimuli
Pain Modulation
• Gate control theory advanced by Melzack and Wall
in 1965 focused on descending pathways from the
brain to the spinal cord that inhibit pain signaling
•
• Current view: signals originating in the brain can both
inhibit and facilitate pain signal transmission
• Neurotransmitters involved in these pathways include
• Endogenous opiates (enkephalins, dynorphins, betaendorphins)
• Serotonin
• Norepinephrine
Pain Control Theories
• Gate Control Theory
• Central Biasing Theory
• Endogenous Opiates Theory
Gate Control Theory
• Melzack & Wall, 1965
• Substantia Gelatinosa (SG) in dorsal horn of
spinal cord acts as a ‘gate’ – only allows one
type of impulses to connect with the SON
• Transmission Cell (T-cell) – distal end of the
SON
• If A-beta neurons are stimulated – SG is activated
which closes the gate to A-delta & C neurons
• If A-delta & C neurons are stimulated – SG is
blocked which closes the gate to A-beta neurons
Gate Control Theory
• Gate - located in the dorsal horn of the spinal cord
• Smaller, slower n. carry pain impulses
• Larger, faster n. fibers carry other sensations
• Impulses from faster fibers arriving @ gate 1st inhibit pain
impulses (acupuncture/pressure, cold, heat, chem. skin irritation).
Brain
Gate (T
cells/ SG)
Pain
Heat, Cold,
Mechanical
Central Biasing Theory
• Descending neurons are activated by:
stimulation of A-delta & C neurons, cognitive
processes, anxiety, depression, previous
experiences, expectations
• Cause release of enkephalins (PAG) and
serotonin (NRM)
• Enkephalin interneuron in area of the SG
blocks A-delta & C neurons
Endogenous Opiates Theory
• Least understood of all the theories
• Stimulation of A-delta & C fibers causes release of Bendorphins from the PAG & NRM
Or
• ACTH/B-lipotropin is released from the anterior
pituitary in response to pain – broken down into Bendorphins and corticosteroids
• Mechanism of action – similar to enkephalins to block
ascending nerve impulses
• Examples: TENS (low freq. & long pulse duration)
Goals in Managing Pain
• Reduce pain!
• Control acute pain!
• Protect the patient from further injury
while encouraging progressive exercise
Other ways to control pain
• Encourage central biasing – motivation,
relaxation, positive thinking
• Minimize tissue damage
• Maintain communication
• If possible, allow exercise
• Medications
Romance
• 10 month old Golden
Retriever
• 2 weeks history of lip
twitches & abnormal
behavior
• Mild CP deficit in R
rear leg
S
Romance
• Localization of Lesion
Cerebral (Forebrain)
O
•
•
•
•
•
•
•
•
•
•
•
D
A
M
N
N
I
I
I
T
T
V
Genetic
Liver Disease
Brain Tumor
Encephalitis
GME
Epilepsy
Romance
• Problem List
1. Facial Twiches
• Differential Dx
• ?
2. Ataxia
3. Behavioral Change
1.
2.
3.
4.
5.
Inf/Inflam
Neoplasia
Inborn Error
Liver
Epilepsy
• Diagnostic Approach
• ?
• Treatment
P
• ?
Romance- -Diagnostic Approach
• MDB
•
•
•
•
•
•
•
•
CBC
Chemistry Profile
UA
Chest & Abdominal
Radiographs
Abdominal Ultrasound
Bile Acids
Cholinesterase
Ammonia level
• Neurologic Tests
• EEG
• CSF Analysis
• Cisternal
• Titers
• MRI
P•
Client Education
Romance- -CBC
O
Romance- -Chemistry
O
Romance- -UA
O
Romance- -MRI
L
O
L
Romance- -CSF Analysis
•
SPECIMEN: CSF – AO
•
•
•
•
Color/Transparency:
Protein mg/dL
RBC/μL
WBC/μL
•
A 32 cell differential count yielded the following:
•
•
•
colorless/clear
16
46
14
13 Neutrophils
5 Lymphocytes
14 Mononuclear phagocytes
•
Two cytospin preparations are stained and microscopically examined. The slides are
of adequate staining and preservation of cellular detail with scant hemodilution
present against a colorless background that contains occasional squamous epithelial
contaminants. Approximately equal numbers of mature, nondegenerate neutrophils
and variably reactive mononuclear phagocytes are the predominant cell types. Small,
well-differentiated lymphocytes are infrequently identified.
•
No infectious agents or neoplastic cells are identified.
•
Interpretation: Mild, mixed pleocytosis.
O
Romance- -Titers (Serum)
• 3DX - Negative for Dirofilaria immitis antigen, Borrelia
burgdorferi and Ehrlichia canis antibody.
• RMS - Negative for Rickettsia rickettsii IgG AB by IFA: Titer <64
• BLM - Negative for Blastomyces by AGID.
• DIS - CDV
IgG AB: 50
IgM AB: Negative
• CRC - Negative for Cryptococcus antigen by latex agglutination
test
• TO1 – Toxoplasma
O•
IgG AB: Negative
IgM AB: Negative
NEO - Negative for Neospora caninurn IgG AB by IFA: Titer <50
Romance- -Final Diagnosis
Seizures Secondary to
GME
A
Romance- -Client Education
• The prognosis is guarded to poor
• May continue to progress over 3-6 months
• Treat
• phenobarbital
• anti-inflammatory and anti-cancer drugs
• Consider CAVM & TCVM approaches to
augment or instead of Western therapy
P
Romance- -TCVM exam
• Tongue
• TCVM Diagnosis
• Red/purple
• Pulse
• Superficial
• Slippery
• Fast
• Sensitivity
• BL 15
• Nao Shu
• Damp Heat with
Internal Wind
Romance- -TCVM Therapy
• AP
• Herbal
• Cranial points
•
•
•
•
•
GV 20
GV 21
An Shen
Meng Men (staple)
GB 20
• Cancer points
•
•
•
•
•
•
LI 4
PC 6
GV 14
SP 9
ST 40
LIV 3
• Mind Damp Heat
Formula
• Jing Tang
• Di Tan Tang
• Jing Tang
Mansion of Mind Damp-Heat
Encephalitis, SRME, GME
Lonicera Jin Yin Hua
Forsynthia Lian Qiao
Isatidis
Ban Lan Gen
Astragalus Huang Qi
Akebia
Mu Tong
Platycodon Jie Geng
Licorice
Gan Cao
Clear heat, Expel wind
Clear heat, Detoxify
Clear heat, Cool blood
Move Qi (stimulate immune system)
Drain Damp-Heat
Transporter
Harmonizer
20 gm
20 gm
20 gm
20 gm
10 gm
15 gm
10 gm
Cody
• History of brainstem
tumor
• leading to secondary
hydrocephalus
• ~2.5cm mass
• Probable
meningioma
• TCVM Dx
• Blood Stagnation
Cody (13 months)
• Western Rx
• Phenobarbital
• Prednisone
• TCVM
• Stasis in Mansion of
Mind formula
• Di Tan Tang
• Max formula
Electro-acupuncture techniques
History
• After electro-acupuncture (EA) analgesia was found
effectively to perform a surgery in China in the early
1970's, EA has been widely used in TCM practice.
Advantage:
•
•
•
•
More effective
Less treatments
Less acupoints
Save labor to manipulate the needles (Classically, the
needles should be manipulated every 2 to 3 minutes).
• Objective control of frequency and amplitude
• Amplitude (intensity of stimulation): a tolerance level
• Frequency:
• Low level: pain ----> beta endorphin mediated
• High level: internal medicine > serotonin mediated
Methods: Acupuncture Points: 6 to 10 points
Frequency: 20 Hz Or 80 to 120 Hz
Electrical intensity: gradually goes to the
points the patient can tolerate.
Indications:
•
Pain management
• Bi syndromes (arthritis)
• Soft tissue injuries
• Disc problems
• Colic/abdominal pain
•
Peripheral nerve paralysis
• Facial
• Radial
• Others
•
Gastrointestinal conditions: vomiting, diarrhea,
constipation, indigestion
•
Muscle atrophy
•
Contraindications:
•
•
•
•
1) Weak/deficient patients
2) Heart problems
3) Seizure/epilepsy
4) Tumor
How to Use EA
1. Dial the AMPLITUDE and FREQUENCY to zero;
2. Plug the wire leads into sockets 1 to 7 and fasten the clips to the handles
of needles;
3. Set the desirable frequencies and wave forms
Frequency:
•Low frequency (F1 = 20-30 Hz)
•Indication: pain conditions---Endorphin release
•Moderate frequency (F1=80 to 120 Hz)
•Indications: internal medical conditions (diarrhea etc)- -Enkephalin
•High frequency (F1=200 Hz)
•Indication: pain conditions- -Serotonin release
How to Use EA
Wave Form: depends on how F1 and F2 is set up
•Continuing Wave:
F1=20-200; F2=0
•Indications: pain conditions
•Intermittent wave:
F1=0; F2=40
•Indications: muscular atrophy
•Dense and Disperse (DD) wave: F1=80; F2 =120
•Indications: nerve paralysis and internal medical conditions
How to Use EA
4. Turn on the power 3
5. Gradually increase AMPLITUDE buttons until the patient can
tolerate.
a) Can increase amplitude a little bit every 5 minutes.
6. The duration of a treatment session: 10 to 30 minutes.
4. Turn off power to terminate the acupuncture treatment.
EA: how to pair the points
The general rules: The same lead to pair 2 points
• 1) Bilateral connection
•
•
•
•
•
a. Pair BL-54 on left side to right BL54 for hip dysplasia;
b. Hua-tuo-jia-ji on the left to right side for disk diseases
c. BL-21 on the left to right BL-21 for vomiting
d. KID-1 on the left to right KID-1 for rear weakness
e. Left Ding-chuan + right Ding-chuan for cough
• 2) Same Channel connection.
• a. GV-14 + Bai-hui for disk disease
• b. LI-10 + LI-15 on the same side for shoulder pain
• c. Tip of tail + GV-20 for vestibular dx, disk disease
• 3) Local connection
• a. TH-14 + LI-15 on the same side for shoulder pain
• b. GB-34 + ST-35 on the same side for stifle pain
• 4) Same energetic connection
• ST-36 + GB-34 on the same side for vomiting, rear weakness
• ST-36 + BL-20 on the same side for SP Qi deficiency
EA: how to pair the points
• 5) From the top to bottoms for paralysis
• a. BL-54 + KID-1 for rear limb paralysis
• b. PC-8 + GV-14 for front limb paralysis
• c. GB-21 + HT-3 for front limb paralysis
• 6) Cover large areas
• a. BL-20 on the left + right BL28 for T-L-S IVDD
• 7) Normal area to sick area
• a. BL-21 to KID-1 for no deep pain caudal to BL-22
• b. ST-5 left to right for right facial paralysis
EA: how to pair the points
• But, we must pay attention to the following:
• 1) The wire (lead) should NOT be connected around
the abdominal areas for pregnant moms.
• 2) The wire (lead) should NOT be connected through
the chest if the patient has a pacemaker.
• 3) The wire (lead) should NOT be connected through
the tumor mass.
• 4) Caution for seizure dogs when using EA
GOD cures, Doctors send the
bill!
-Mark Twain