PAIN:

Pathomechanism & Clinical Diagnosis

Trianggoro Budisulistyo

Dept of Neurology Diponegoro University Semarang

Pain is the 5th vital sign initially
promoted by the American Pain Society (APS)
referred to more aware of pain syndromes &
treatment also → serious management &
screening the unrelieved pain mechanism
James Campbell, MD
Presidential Address, American Pain Society
November 11, 1996
• PAIN is an unpleasant sensory &
emotional experience associated with
actual or potential tissue damage or
described in terms of such damage

• True for Acute Pain which is our friend

• Chronic Pain is a false alarm, it is a
disease itself
– Persistant more than 6 months
– Not amenable to routine pain control methods
– Exists beyond an expected time frame for healing
– Healing process may never occur

Boswell MV, et al. Pain Physician Vol. 8, No. 1, 2005

“..Pain refers the clinical symptoms due to
lession or disease that altered simultantly
by biochemistry, physiology, or
psychology which related with CNS
(sensory), mood, cognitive process and
psychodynamic"
- Bonica -
 P–A–I–N

Place: where is the pain?

Aggravating factors: what makes the pain worse?
Intensity/severity: VAS score, Wong Baker's face
scale
Nature factors: describe your pain? What relieves the
pain?
 Principle Clinical Examination
• Sacred 7 + Fundamental 4
– Chief Complaints
– Onset
– Location
– Accompanying SUmptoms
– Chronology
– Aggravating Factors
– Extenuating Factors
– History of Illness
– Family
– Social States
– Clinical Founding
– Summary
 Understanding of Pain

• Tissue damages • Anatomies

• Pain perception • Physiologies
• Suffering of Pain
• Psychology
• Behavioral of Pain
 Clinical Terms of PAIN Mechanism
• Allodynia ≈ painful response to a normally stimulus
• Central pain ≈ a lesion or disease of the central somatosensory nerves
• Central sensitization ≈ ↑ nociceptic response in the CNS to normal or
subthreshold sensory input
• Deafferentiation pain ≈ a partial or complete loss of sensory input after
lesions in somatosensory pathways
• Descending modulation ≈ descending impulse modified to somatosensory
information resulting in increased or decreased pain
• Ectopic discharge ≈ spontaneous electrical nerve impulses that occur
spontaneously without stimulation or originate at sites after nerve injury
• Ephaptic transmission ≈ two independent nerves communicate with each
other through an artificial synapse (after injury to the insulating myelin
sheath)
• Hyperalgesia ≈ Increased pain response to a normally painful stimulus
 Clinical Terms of PAIN Mechanism
• Neuropathic pain ≈ lesion or disease of the somatosensory nerves
• Neuroplasticity ≈ lesion or disease of the somatosensory nerves
• Nociception ≈ lesion or disease of the somatosensory nerves
• Nociceptive pain ≈ from actual or potential damage to non-neural
tissue (visceral or somatic)
• Noxious stimuli ≈ damages or threatened events to damage
normal tissues
• Peripheral sensitization ≈ lowering the pain threshold & ↑ nerve
impulse (hyperexcitability)
• Sympathetically maintained pain ≈ abnormality of the sympathetic
nervous system
• Windup ≈ ↑frequency & magnitude of firing of dorsal horn
neurons (repetitive activation of C fibers above a critical threshold)
→ perceived increase in pain intensity
 Receptors
Non-painful stimuli:
• Specificity for a particular stimulus
• High degree of gain to amplify weak signals
• Rapid adaptation to increasing intensities

Painful stimuli:
• Specificity less important
• High threshold receptors: thermal, chemical and
mechanical stimuli (polymodal)
• Threshold for firing may decrease

Kidd, Urban. Br J of Anaesth 87, 2001.

Hyperalgesia Sensitization

pain threshold threshold for response

pain to suprathreshold response to

stimuli suprathreshold stimuli

Spontaneous pain Spontaneous activity

 Physiology of Pain
Brain

Descending Perception
Pathway

Ascending
Pathway
Spinal
C-Fiber
Cord
α-β Fiber
Dorsal
α-δ Fiber Horn

Conduction Transmissio
Dorsal
Root
n/Modulation
Peripheral
Nerve Ganglion

Transductio Injury
n

1. Galer BS, Dworkin RH. A Clinical Guide to Neuropathic Pain. Minneapolis, MN: McGraw-Hill; 2000.
2. Irving GA, Wallace MS. Pain Management for the Practicing Physician. New York, NY: Churchill Livingstone; 1997.
3. Woolf CJ, et al. Ann Intern Med. 2004;140:441-451.
Sensory Pathway
The left half of this sectional view shows important anatomical
landmarks; the right half indicates the functional organization
of the gray matter in the anterior, lateral, and posterior gray
horns.
 Pathomechanism of Pain
• Nociceptive pain
– Believed to be related to ongoing activation of an
intact nervous system by tissue injury
• Somatic
• Visceral
• Neuropathic pain
– Believed to be related to aberrant
somatosensory processing in the peripheral
nervous system, the central nervous system,
or both
 Nociceptive vs Neuropathic Pain
NOCICEPTIVE PAIN MIXED PAIN NEUROPATHIC PAIN

CRPS type 2
Post
Sugical
Cancer Pain
Arthritis

Neuropathic Trigeminal
Mechanical LBP Sickle cell
LBP Neuralgia
crisis
Post Herpetic Neuralgia
Sport Injuries
Distal Polineuropathy
(diabetic, HIV)
*Complex regional pain syndrome type II. Easy NEP, 2005
16
Nociceptive PAIN Mechanisms
PERCEPTION
Clinical expriences that integrated cognitive &
affectve (emotional) responses
Opioid

MODULATION/ TRANSFORMATION
≈ Plasticity
Nociceptive signals modulate at synaptic site & the level of
CNS (ascending, descending, regional facilitation or
inhibition)

TRANSMISSION
Noxious stimuli enters the cord (DRG) thus transfer
information to the CNS
Non Opioid, Anticonvulsant, Antidepressant, Opioid

TRANSDUCTION
Tissue injury activates nociceptors A-delta & C-fibers
(mechanoreceptor, polymodal nociceptor)
Analgesics, Non Opioid
 Nociceptive Pain

• Associated with tissue damage

• Usually responsive to non opioids and/ or opioids
• Somatic Pain; bone, joint, muscle, skin or connective
tissue → aching or throbbing in quality and is well
localized
• Visceral Pain; visceral organs such as the heart, GI
tract, and pancreas. This may be sub-divided:
– Tumor involvement of the organ (aching and fairly well
localized pain)
– Obstruction of hollow viscous (intermittent cramping and
poorly localized pain)
Mechanisms of nociceptive central pain

1. Autosensitization of receptors
2. Ectopic firing of DRG cells
3. Calcium-induced molecular cascades
from excess glutamate
4. Phenotypic change of A-β cells and DRG
5. Changes in gene expression of sodium
channels and neuropeptides
6. Anatomic changes at dorsal horn
Schwarzman et al. Neurological Review, 58, 2001.
 Tracey, 2008

INJURY SYMPTOMS
Spontaneous
Tissue Damage
Hyperalgesia Allodynia
Pain

CENTRAL
PERIPHERAL
ACTIVITY SENSITIZATION

Decreased Increased
threshold to
peripheral stimuli Expansion of Spontaneous
Nerve Damage Receptive field activity
 Peripheral Sensitization
Tissue Damage Inflammation Sympathetic Terminals

SENSITIZING ‘SOUP’
Hydrogen Ions Histamine Purines
Noradrenaline Potassium Cytokines
Bradykinin Prostaglandins NGF
Leukotrienes 5-HT Neuropeptides

Woolf, Chong. Anesth. Analgesia (77), 1993.

 Peripheral Sensitization
Plasma Extravasation
Vasodilation
SKIN
TNF-α
IL-6
Mast Macrophage LIF
Tissue
Cell Damage
Pressure ?
Heat Bradykinin
5-HT3 Histamine PGE2 IL1ß NGF ATP H+

VR1 5-HT3 H1 EP B1/B2 IL1-R TrkA P2X ASIC

H+
Ca2+

(PKC)
PKA Peripheral
PKC TTXs Nerve
Gene
TTXr
(SNS/SNS2) Regulation Terminal
TTXr
Sub P

Adapted from Woolf CJ, et al. Science. 2000;288:1765-1768.

 Neuropathic PAIN Mechanisms
• ≈ is a chronic pain state resulting from peripheral or
central nerve injury either due to acute events (
amputation, spinal cord injury) or systemic disease
(diabetes, viral infection, cancer)
• Peripheral Process
– Nerve injured
• Central Process
– Sub threshold noxious stimulus → postsynaptic activation → central
sensitization (hyperalgesia)
• Descending Modulatory Pathways
– Periaquaductal gray area (PAG), locus coeruleus, nucleus raphe magnus,
nuclei bulbar reticular formation ≈ descending modulatory pathways → pain
signal enhanced

Vranken JH. Central Nervous System Agents in Medicinal Chemistry, 2009;9 :

 Neuropathic Pain
…Pain caused by a lesion or dysfunction
of the nervous system1
• Nerve sensitization or damage
can be located in the peripheral
or central nervous system1
• Manifests with sensory symptoms
and signs2
• May have both positive and
negative sensory and motor symptoms and
signs2

1. Merskey H, Bogduk N, eds. Classification of Chronic Pain. 2nd ed. Seattle, WA: IASP Press; 1994.
2. Backonja MM. Anesth Analg. 2003;97:785-790.
 Neuropathic Pain
• Usually responsive to adjuvant analgesics
• Centrally Generated Pain → NYERI TAJAM
– Peripheral or central nervous system injury: phantom pain, SCI,
post Stroke
– Sympathetically maintained pain associated with dysregulation
of the automatic nervous system: reflex sympathetic dystrophy
– Nonsympathetically mediated pain: post-herpetic neuralgia,
neuroma formation
• Peripherally Generated Pain → NYERI TUMPUL
– Pain that is felt along the distribution of many peripheral nerves
(e.g diabetic neuropathy)
– Pain that is usually associated with a known peripheral nerve
injury
 History and Symptoms
• Centrally Generated Pain → NYERI TAJAM
– Peripheral or central nervous system injury: phantom pain,
SCI, post Stroke
– Sympathetically maintained pain associated with
dysregulation of the automatic nervous system (≈ RSD)
– Nonsympathetically mediated pain: post-herpetic neuralgia,
neuroma formation
• Peripherally Generated Pain → NYERI TUMPUL
– Pain that is felt along the distribution of many peripheral
nerves (e.g diabetic neuropathy)
– Pain that is usually associated with a known peripheral nerve
injury
26
 Basic Mechanism of NP 2
Peripheral Effect Central Effect
• Ectopic and spontaneous • Central sensitization
discharge • Spinal reorganization
• Alterations in ion channel • Cortical reorganization
expression • Charges in inhibitory
• Collateral sprouting of pathways
primary afferent neurons
• Sprouting of sympathetic
neurones into the DRG
• Nociceptor sensitization

Bridges, 2001
27
 Ion Channels
• Dynamic, constantly changing
• Plasticity reflects sensitivity needed for
survival
• Injury: amygdala, hippocampus, and DRG
• Normal peripheral nerves (resist)
• Demyelination: density
 Plasticity in Chronic Pain
Injury
Acute Pain

Normal Healing Healing With Plasticity

Pain Relief Hyperalgesia Allodynia

Chronic
Pain

Adapted from Marcus DM. Am Fam Physician. 2000;61:1331-1338.

 Classification of Pain

• Onset of Duration: Acute, Chronic

• Pain Source of Origin: Muskulosceletal
(MSK), Visceral Organs, Nerve Injury
• Etiologies: Vascular, Inflammation,
Herediter, Trauma, Autoimun, Metabolic,
Neoplasms, Degenerative, Psychogenic
• Types of Pain: Physiologic, Nociceptic,
Neuropathic
 Assesment of Pain
• Immediate Pain: Intensity, Location, Affective
Response, Composite Measures
• Physical Functioning: Impairment, Functional
limitation, Disability
• Psychological Factors: Influence vs.
causation, Mediation, Reinforcement,
Resonators, Pain beliefs
• Pain Behaviors: Observation, Role of learning
• Objective Correlates
 Management of Pain
• Pharmacologic
• Psychological
• Other somatic treatments
• Importance of Multimodal
• Cormorbid treatments
• Role of C/L Psychiatrist
 Ideal for pain management is to measure the symptoms and to
treat the pain mechanisms

Disease/ Injury
Identification of the
underlying mechanism is
TREAT Mechanism difficult

Symptoms are not always

MEASURE Signs/ Symptoms equivalent to the
mechanism

Syndromes
Basic Strategies of Pain Control

DeLeo JA, Winkelstein BA. Spine. 2002; 27(22): 2526-37

 Management of Pain:
Pharmacologies
STEP 3
( ≈ Free from cancer pain)
Opioid ± Non opioid
STEP 2 adjuvant analgesic
Opioid ±
adjuvant analgesic
± Non opioid
STEP 1
Non Opioid or ±
adjuvant analgesic
WHO's
ANALGESICS LADDER
Pain threshold Pain tolerance

0 1 2 3 4 5 6 7 8 9 10
mild moderate severe
IASP: Neuropathic Pain Treatment

Antidepresan trisiklik, Duloxetin,

Gabapentin,
Pregabalin, Lidokain topikal

Lamotrigin, Topiramat, Valproat,

Mexiletine, NMDA,
Kapsaisin topikal
IASP: International Association for the Study of Pain
36
Analgesics Prescription Issues
 Interventional Pain Management
• Developing of pain management requires to knowing
which approach is proper for our patients
– Pharmacologic, Psychological, and/ or Interventional/ Invasive treatments
– BENEFITS >< DISADVANTAGES are the critically concern
• IPMs have been developed as a new technique since
1960
– Thus progress with the efforts of John J. Bonica (1975), Steven Waldman first
used this word in 1996
– → Pathophysiology, Pharmacology, Physical treatments,
Emergency precaution, Palliative care
• The field of IPMs including DIAGNOSIS & TREATMENT of
pain:
– Nerve blocks, Anesthetic or corticosteroid injection, Intrathecal
opioids, Neuroablation/ Neurolysis, Nerve stimulation , Intrathecal
pump
Interventional Pain Management
• Block Procedures: joints, local
anesthetic/ steroid
• Neuroaxial Procedures
• Neuroabaltion & Neurolytic
Procedures
• Intradiscal Procedures
• High-End Procedures
• Regenerative Treatment
Procedures
BLOCK PROCEDURES
NEUROAXIAL PROCEDURES
 Caudal Epidural

• Dural sac ends at S2 (may be at S1/S3

in some)
• Indications
– spinal canal stenosis, HNP,
coccigodynia, sacral radiculitis, rectal
pain, pudendal neuralgia, sacral
fracture, post radiation sacral
radiculopathy, tumor metastatic
• Contraindications
– infection, coagulopathies,
anticoagulant treatment, pregnancy
(semester 3)
• Potentially bleeding HIGHER than other
epidural procedures
 Transforaminal Epidural

pedicle
• Inflammed nerve injection:
– HNP (posterolateral
dural sleeve
“safe” triangle
dorsal root
gangion
spinal nerve
compression
– Lateral Stenosis
ventral
ramus

dorsal
ramus

c c

b b
needle

a a

A B
Interlaminar Epidural
 Epidurolysis

• Initially described by Gabor Racz (1989),

known as percutaneus epidurolysis
– Lytic the tissues adhession surrounding
the cord → reduced the stretched or
sticky nerve roots either dura

• Improved pain relief in 71-76% cases

(epidural steroid approximate 50%) for 2
years
– If 3-6 months after the procedure & the pain
still remain so refer to surgery
• Narrowing of spinal canal due to Spinal Canal Stenosis
addressed:
– Nerve roots compression (also bone & soft tissues
surrounded): radicular pain
– Reduce of local neurovascularization: cauda equine
syndromes, venous congestion, raised of intraepidural
pressure, neurogenic claudication
• Prevalence: 27,2% (mostly asymptomatic, imaging founded)
 Foraminal Stenosis Lateral Recess Stenosis

• Root symptoms • Claudication

• Unilateral • Radicular pain
• No claudication • Weakness is rare
• Acute or chronic • Acute or chronic
 Spinal Cord Stimulation
Electrical stimulation of the dorsal spinal columns (and perhaps
deeper structures)
Achieved with the use of an electrical array to deliver the current
using various sources
Used as a high end procedure in cases with intractable chronic
pain not responsive to other less invasive maneuvers
Pain treatment that delivers low-voltage electrical
stimulation to the spinal cord to inhibit or block the
sensation of pain
Gate Control Theory – A beta inhibits C fibers
Increased Dorsal Horn Inhibition (GABA)
Decreased Sympathetic Efferent Output

51
 Spinal Cord Stimulation

Failed Back Surgery Syndrome

Chronic Lumbar Radiculopathy
Chronic Regional Pain Syndrome
Peripheral Vascular Disease
Ischemic Heart Disease
Spinal Cord Stimulator
NEUROABLATION &
NEUROLYTIC
 RF's Mechanism of Action

• The Continuous Radiofrequency (CRF)

– This applying temperature of the tip is 45 - 75°C →
afferent nerve fibers and tissues destruction (induce
coagulation and cell death)

• The Pulsed Radiofrequency (PRF)

– This is applying the RF currents in a pulsatile manner with
cooling periods (of about 480 ms) separating the heating
periods (of about 20 ms)
– delivers a large current density of about 20,000 A/m2 and
50,000 Hz in 20-ms pulses at a frequency of 2 per second,
the temperature not exceed 42°C
 RF's Mechanism of Action

 INHIBITION OF NOCICEPTIVE FIRING

- PRF disrupts impulse transmission in small unmyelinated C & Aδ -
fibers without neuroablation or thermal destruction (≈ long-term
depression)
- membrane changes may prevent the transmission of ions needed
for pain impuls propagation
- damage to mitochondria (membranes fragility) → ATP mediated
cells interrupted & cellular metabolism → impending the
generation of pain signals
- microtubules & microfilaments damaged → impede pain
transmission
- C-fos expressing in dorsal horn → inhibitory interneurons
(nociceptive reduced)
 RF's Mechanism of Action

• Lesion area- increased by rotating the tip of the cannula (18-gauge,

100-mm cannula with 10-mm curved active tip) 180°
• Lesion size is enlarged by 2 mm when the cannula size is increased
from 20 gauge (A) to 18 gauge (B).
Gofeld, Michael; Faclier, Gil..Pain Medicine, Mar2008,
 RF's Neurablation Steps

– Current at radio wave frequency (100,000 - 500,000 Hz)

– Involves current passing through an electrode →heating and
destroying surrounding tissues
– Electromagnetic field surrounding the tip (pulsed RFA): 2-3 mm
– The generator output is set for the electrode tip temperature not to
exceed 42-45°C → less neurodestructive

Boxem KV, Eerd MV, Brinkhuize T, Patijn J, Kleef MV, Zundert JV. Pain Practice. Volume 8, Issue 5,
September/October, 2008. pp: 385–93
 Neurolytic Blocks

• Interrupted the nociceptic pathway from periphery to

the spine cord
– Mechanical (surgery), Thermal (cryoneuroablation),
Chemical (alcohol, phenol)
• Neurolytic block commonly performed for refractory
cancer pain
– → maximize the analgesic effects of opioid or nonopioid
analgesics and also reduce the dosage of these agents
 Neurolytic Blocks

• Neurolytic blocks aim to cause Wallerian

degeneration of the nerve fibre → pain interrupted
– this damaged tend to regrow over months, with the
potential for the return of pain

• The chemical neurolytic agents: phenol (6-10%),

ethanol (50-100%)
– Clinical application: intrathecally, plexus blocks (coeliacus,
lumbar), cranial nerves, paravertebral
– Complications: orthostatic hypotension, back pain, neuritis
(somatic blocks), aorta dyssection, paraplegia, bladder or
bowel dysfunction, saddle block
 Sphenopalatine Ganglion

Clinical Application
Cluster Headache

Complication
 hematoma formation, epistaxis (rare), palatal numbness, maxillary
nerve damage, diplopia (due to LA spread)
 Gasserian Ganglion

Clinical application
 Trigeminal neuralgia, cluster headache, intractable occular pain, oral or
facial cancer pain, post intracranial or microvascular surgical neuralgia,
occular pain due to Glaucoma
Complication
 Dysthesia & anesthesia dolorosa, loss of corneal reflex, neurolytic
keratitis, visual loss, retrobulbar hematoma, motor weakness (mandibular
branch), carotid puncture, meningitis, incidental intracranial placement of
electrode, occulomotor paralysis, cavernous sinus fistula
 Stellate Ganglion
Clinical application
CRPS (upper limb region), acute herpes zoster, cancer pain (head and
neck and upper extremities), "chest pain from angina", hyperhydrosis

Complication
 vascular penetration, pneumothorax, esofagus or trache penetration
 Thoracic Sympathetic

Clinical application
 Pain in upper region (chest wall, thorax, upper abdominal viscera),
acute herpes zooster, PHN, post mastectomy

Complication
 Pneumothorax, bleeding (aorta penetration), infection, hypotension
 Coeliac & Sphlancnic Plexus
Clinical application
 Pain originated from: pancreas, liver, gall bladder, omentum, mesentery,
aliementary tract (stomach - transverse part of large colon)
Complication
 Pain during and after procedure, orthostatic hypotension, diarrhea,
vascular penetration, renal/ urinary tract linjury, lumbar somatic nerve injury,
pneumothorax, chylothorax, ejaculation dysfunction, abscess, peritonitis,
retroperitoneal hematoma, subarachnoid or epidural injection, paraplegia
 Lumbar Sympathetic

Clinical application
 Sympathetically mediated pain (kidneys, ureters, genitalia, lower
extremities), phantom limb pain, reflex sympathetic dystrophy (CRPS),
causalgia, peripheral neuropathies, vascular insufficiency of the lower
extremity, post sympathectomy neuralgia

Complication
 vascular penetration, hematuria, epidural/ intrathecal injection
 Ganglion Impar

Clinical application
 Sympathetic mediated pain of perineal region, malignancies of
pelvis and perineum, chronic benign pain syndromes like
perineal neuralgia & coccydynia
Complication
 periosteitis, visceral perforation, epidural spread, coccydynia
INTRADISCAL PROCEDURES
 Intradiscal electrothermal therapy
(IDET)
• Is a procedure for the treatment of
discogenic low back pain
– A specially designed catheter system (SpineCATH) is
introduced into the posterior part of the disc space via
a posterolateral percutaneous approach
– The posterior parts of the disc space are heated up to
a tissue temperature of about 75° C to achieve
contraction of the collagen fibers in the posterior
annulus fibrosus
HIGH-END PROCEDURES
 Epiduroscopy

• The procedure mainly used an endoscope

– ≈ Clear visualization of anatomical structures (dura mater,
vessels, connective tissue, nerves and fatty tissue,
adhesions, sequesters, inflammatory processes, fibrosis
and stenotic changes)
– Mechanical or laser mobilisation of spinal adhesions, or
application of steroids to inflamed tissues, may also be
performe
– Complications: injury on the nerve, spinal cord or dura,
infection, development of a hematoma (blood clots), retinal
detachment
 Spinal Cord Stimulator (SCS)

Possible Mechanisms of action :

- Inhibit the tranmsmission of unmyelinated C fibers and
myelinated A fibers
- Segmental, antidromic activation of A-beta afferent (gate control
theory)
- Blocking of transmission in the spinothalamic tract
- Supraspinal pain inhibition
- Activation of central inhibitory mechanisms influencing
sympathetic efferent neurons
- Activation of putative neurotransmitters or
neuromodulators
 Spinal Cord Stimulator (SCS)

• Indication
– Failed back surgery syndrome (FBSS)
– Complex Regional Pain Syndrome (CRPS) Type I-
II
– Chronic Lumbar Radiculopathy
– Peripheral Vascular Disease
– Ischemic Heart Disease
 Transforaminal Endoscopic
Procedures
• Endoscopic foraminal approach can be utilized for
most lumbar disc herniations and for the diagnosis
and treatment of degenerative conditions of the
lumbar spine, consider to:
– Larger blood loss during surgery
– Delayed post-operative recuperation
– Increased hospital stay (LOS)
– Delayed return to functional status
– Extensive scar tissue formation at operated area and into
the epidural space

• → able to reach, visualize, and treat intradiscal

and foraminal pathologic lesions without
destabilizing the posterior muscle column and
facets
REGENERATIVE TREATMENT
PROCEDURES
 Mechanism of Action
• Local injection (needle's hit) causes local
injury

• Promotes inflammation cascades: influx of

granulocytes, macrophages, fibroblasts,
growth factors

• Ultimately, collagen deposition leading to

strengthened ligaments (decreased pain)
 Dextrose
• Gustav A. Hemwall (1980's) was the first
admissen dextrose solution for RIT
– Dextrose <10% stimulated the cells and
tissues proliferation without inflammation
reaction
– Dextrose >10% caused concentrated gradient
outside of injection's site (initiated wound
healing process)
 Platelet Rich Plasma (PRP)
• Platelet activation → clotting cascade initiation →
growth factors release (TGFβ, IGF, VEGF,
EGF,FGF-2) → stimulate: connective tissues
collagen proliferation, new blood vessels & tissue
regeneration and healing
Platelet Rich Plasma (PRP)
Connective Tissues Proliferation
Connective Tissues Proliferation
Summary: “a gain in pain”
Pain managements required to
Efficient - Effective...
 Eyes don't see if
the brain doesn't know....

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