Referred Pain

Referred pain and headache
Nabih M Ramadan, MD, MBA

Chief Medical Officer,
Division of Developmental Disabilities, Nebraska HHS
Clinical Professor of Neurology,
Loyola University, Chicago
Objectives
1.
2.
3.
To discuss basic mechanisms of

referred pain
To identify medical conditions of
referred pain in the head and neck
To translate mechanistic
understanding of conditions of
referred pain into effective therapy
Pre-test
Q1: choose best answer
{
Suggested mechanisms of referred pain

include all of the following except:
A.
B.
C.
D.
Convergence theory
Neuro-glial signaling theory
Hyperexcitability theory
Gating theory
Pre-test
{
Examples of referred pain include:

A.
B.
C.
D.
E.
F.
Cervicogenic headache
Jaw pain with angina pectoris
Forehead pain with carotid dissection
Sharp, localized pain
All of the above
A,B, and C only
Pre-test
Q3 : True or false statements
{
Activation of nociceptors on posterior

inferior cerebellar artery branch of
vertebral artery are mostly felt in the
forehead region
Pre-test
{
Referred pain is conveyed from the

periphery by A-delta and C-type fibers
Pre-test
Q5: Best match
1.
2.
3.
4.
5.
Extension of
trigeminal nucleus
caudalis
Sensory nucleus of
cranial nerve V
Ophthalmic branch of
cranial nerve V
Cranial nerve X
C2-3 sensory
branches
A.
B.
C.
D.
E.
Subnucleus
interpolaris
Auricular nerve
Posterior head and
upper neck
Forehead innervation
Substantia gelatinosa
Illustrative case history #1

{
27 year old Caucasian lady presents with:

z
Episodic type I dizziness associated with left

peri-auricular pain and tenderness;
photophobia; and generalized headache.
Symptoms are most pronounced during
menstrual cycles.
Almost continuous type III dizziness
Exam is normal except for marked tactile

allodynia and vertiginous feeling with light
stimulation of left pre-tragus region
Discussion
10
Referred pain
{
{
{
{
Definition
Mechanisms
Manifestations
Management
11
Definition
MW dictionary: a pain subjectively
localized in one region though due
to irritation in another region
{ Pain felt in undamaged area of
body, away from actual injury;
sclerotomic in distribution, felt
distant from its origin
{
12
Referred pain to the head

{
Cranial structures,
z
Facial structures,
z
e.g. meninges, cerebral vasculature

e.g., teeth, rhino-sinuses, TMJ, ear
Neck structures,
z
e.g., trapezius, paraspinal muscles,

upper vertebral periosteum
13
Mechanism: convergence theory

{
Afferent nerve fibers

from one region of the
body or head converge
centrally (spinal cord
for body; spinal
trigeminal tract for
head and upper neck)
with fibers from
another region onto a
common second order
neuron
misinterpretation of
pain source
Goadsby et al. Headache 2008
14
Mechanism: hyperexcitability theory

{
Cross connections between 2nd order neurons

supplying different somatotopic regions
result in pain perception distant from
nociceptive stimulus representation ONLY
when input exceeds a certain threshold
Sensitization sites
15
Expression of hyperexcitability
{
Viscero-sensory, sensory-visceral
z
z
Sensory-special sensory
z
Cardiac ischemia resulting in jaw pain

Stimulation of inflamed superficial temporal
artery resulting in reflex activation of NTS from
TNC interconnections causing nausea
Activation of TNC resulting in vertigo from
activation of NO
Sensory-sensory
z
Activation of TNC via touch resulting in pain
NTS= nucleus tractus solitarius; TNC= trigeminal subnucleus caudalis; NO= nucleus olivarius
16
Neural-glial signaling
{
{
{
Recent evidence for important

role of glia in cross-neuronal
communication via gap
junctions
Signaling noted at the TG level
Might explain referred pain
when one branch of the
trigeminal nerve is activated
and pain is felt in another
division (e.g., TMJD,
rhinogenic headaches)
TG= trigeminal ganglion; TMJD= Temporo-mandibular joint disease

From the laboratory of Paul Durham. Headache, 2007
17
Anatomical/physiological substrates
Relevance to head pain
{
Sensory fibers that distribute with

peripheral branches of VII, IX and X
CNs join STT and terminate in STN
TNC extends into dorsal horn of C13 overlapping with SG
TNC and SG similar anatomically
and functionally
STT= spinal trigeminal tract; STN= spinal trigeminal nucleus; TNC= trigeminal subnucleus caudalis;
SG= substantia gelatinosa
18
Anatomical/physiological substrates
Relevance to head pain
{
Some neurons in all STNs

(TNO, TNI, TNC) respond
regardless of stimulus type
(mechanical, thermal, or
nociceptive)
z
Neurons in TNC respond best

to thermal and nociceptive.
Prominent internuclear
connections between all
trigeminal sensory nuclei
exist
http://thalamus.wustl.edu/course/face.html
STN= spinal trigeminal nucleus; TNO,I,C= trigeminal subnucleus oralis, interpolaris, caudalis
19
Manifestations, some examples

{
{
Migraine
Migrainous vertigo
z
Cervical causes of headache

z
Illustrative case #2
Headache with ischemic cerebrovascular

disease
z
illustrative case #1
Temporo-mandibular joint disease (TMJD)

z
20
21

{
27 year old Caucasian lady presents with:

z
Episodic type I dizziness associated with left

peri-auricular pain and tenderness;
photophobia; and generalized headache.
Symptoms are most pronounced during
menstrual cycles.
Almost continuous type III dizziness
Exam is normal except for marked tactile

allodynia and vertiginous feeling with light
stimulation of left pre-tragus region
22
Migraine associated vertigo

{
{
{
Not a fully accepted entity by IHS

May occur in up to 1% of population1,2
Suggested criteria for diagnosis:3
z
z
z
1-3
Recurrent vestibular vertigo

Migraine according to IHS
Migrainous symptoms during at least two
vertiginous attacks, AND
Vertigo not attributed to another disorder
Neuhauser HK et al, 2005, 2006, 2009
23
Reasons for association

{
{
{
{
Coincidental
Co-morbid (e.g., BRPV, motion sickness)
Shared genetic
Mechanistic:
z
z
z
Olivary-trigeminal reflex and/or connections

Innervation of inner ear by branches of V1
Extension of plasma protein extravasation into
endolymph
BRPV= Benign recurrent positional vertigo
24
Pharmacological management
{
{
{
Depends on the condition

Mostly based on consensus (level C
recommendations by SORT)1
With migraine associated vertigo,
consider conventional migraine
treatments, particularly with
findings of common receptors on
olivary and trigeminal nuclei (e.g.,
5-HT1F, CGRP)2
Lempert et al., 2009. 2Ahn et al, 2009. SORT= strength of recommendation taxonomy; CGRP=
calcitonin gene related peptide
25
26

{
38 YOF complained for about 5 years of

attacks of headache elicited by coughing,
sneezing, and laughing, which have
increased in frequency one year prior to
evaluation
Unremarkable physical and neurological
examination except for short and broad
neck, and subtle hypometric saccades
bilaterally
27
Radiological finding
28
Chiari malformation types

Type
Features
Mildest form. Cerebellar tonsils displaced into

cervical spinal canal. Impairs CSF circulation
II
Most common form. Downward displacement of

the brainstem into the spinal canal in addition to
downward displacement of the cerebellar
tonsils. Meningo-myelocele and spina bifida
III
Type II plus total cerebellar herniation through

foramen magnum, forming encephalocele,
cervical meningocele
IV
Cerebellar hypoplasia
29
Chiari malformation type-I (CMI)
30
General features
{
{
{
Seen on ~0.5% of cranial MRI

3:2 F:M
Most patients are not diagnosed
until adulthood
Over 30% with 5-10 mm herniation
are asymptomatic
31
Clinical manifestations
{
{
{
Headache (most common)

Progressive scoliosis
Signs & symptoms of cerebellar dysfunction (e.g.,
ataxia)
Lower brainstem compression signs and
symptoms
z
z
z
{
{
{
Dysphonia
Frequent respiratory tract infections
Coughing when swallowing foods and fluids
Spinal cord signs and symptoms

Central cord syndrome
Combination
32
Headaches of CMI
{
Chiari distinctive
z
z
Occipital/suboccipital
Aggravated by Valsalva-like maneuvers,
physical exertion and sudden postural changes
Could be
z
z
Short lasting (<5 min), cough-headache

Episodic lasting hours to days, mimicking
migraine (unilateral, pulsating)
Non-remitting, fluctuating. Not precipitated by
Valsalva-like maneuvers
33
Diagnostic criteria
ICHD 7.7
A.
Headache fulfilling B-D and >1 of:

1.
2.
3.
B.
Precipitated by cough and/or Valsalva maneuver

Hrs to days of occipital or sub-occipital headache
Sxs &/or signs of brainstem, cerebellar &/or
cervical cord dysfunction
Cerebellar tonsillar herniation on MRI:

1.
2.
>5 mm caudal descent of cerebellar tonsils

>3 mm caudal descent of cerebellar tonsils plus
>1:
1.
2.
3.
4.
Compression of CSF spaces postero-lateral to

cerebellum
Reduced height of supra-occiput
Increased slope of the tentorium
Kinking of medulla oblongata
International Classification for Headache Disorders (ICHD), 2nd edition, 2004
34
Diagnostic criteria (continued)

ICHD 7.7
C. Evidence of posterior fossa
dysfunction, based on at least two of
the following:
1. Otoneurological symptoms and/or signs
(eg, dizziness, disequilibrium, sensation
of alteration in ear pressure, hypacusia
or hyperacusia, vertigo, down-beat
nystagmus, oscillopsia)
2. Transient visual symptoms (spark
photopsias, visual blurring, diplopia or
transient visual field deficits)
3. Demonstration of clinical signs relevant
to cervical cord, brainstem or lower
cranial nerves or of ataxia or dysmetria
D. Headache resolves within 3 months

after successful treatment of the
Chiari malformation
35
Management
{
{
{
Quite controversial
Individualized
Medical if no signs or symptoms of
brainstem or spinal cord compression
Posterior fossa decompression +
laminectomy
z
Could be complicated by:

{ CSF leak
{ Neural or vascular injury
{ Infection
Claim of success in over 80%
36
37

{
{
{
{
{
42 year old woman developed a sudden, severe and

throbbing right temporal headache 2-3 minutes after
sexual orgasm. Within minutes, she experienced
nausea and photophobia, and perceived bright dots in
both visual fields that spread out centrifugally during
10 minutes. The next morning, her headache improved
dramatically but the nausea and photophobia were as
bad. While driving, she got confused and developed a
left hemiparesis.
PMH: Hypertension on diltiazem. No migraine, cardiac
or cerebrovascular disease.
Social habits: Non-smoker, non-drinker. Separated
Family history and ROS: Non-contributory
Pertinent physical findings:
z
z
Mild left hemiparesis and left tactile extinction

Mild anosognosia
38
Radiological findings
Early Lateral
view
Late Lateral
view
AP
view
39
Referred pain from CVD

{
Pain in distribution
of V1 with middle
cerebral artery
territory stroke
Pain in distribution
of C2 with
vertebral artery
proper or PICA
distribution stroke
CVD= cerebrovascular disease; PICA= posterior inferior cerebellar artery
40
Pain referral pattern
Ray and Wolff, 1940
41
Headache and ischemic stroke

A.
B.
C.
Any new acute headache fulfilling

criterion C
Neurological signs and/or
neuroimaging evidence of a recent
ischemic stroke
Headache develops simultaneously
with or in close temporal relation
to signs or other evidence of
ischemic stroke
International Classification for Headache Disorders, 2nd edition, 2004
42
Headache or facial and neck pain

attributed to arterial dissection
A.
B.
C.
D.
Any new headache, facial pain or neck

pain of acute onset, with or without
other neurological symptoms and signs
fulfilling criteria C and D
Dissection demonstrated by appropriate
vascular and/or neuroimaging
investigations
Pain develops in close temporal relation
to and on the same side as the
dissection
Pain resolves within one month
International Classification for Headache Disorders, 2nd edition, 2004
43
Headache and stroke

{
{
{
Common with hemorrhagic stroke

Up to 35% of patients with ischemic stroke
Headache with ischemic stroke more likely in people
without hypertension, and when stroke is in the
posterior circulation territory1
Can be:
z
z
z
Varied phenotypes
z
z
z
Mitsias et al.
sentinel d-3 to d-0

Onset d0 to d-3
Delayed >d-3
Migraine-like
Tension-type like
Trigeminal autonomic cephalgia like
Increased risk of dissection in migraineurs compared to

controls
44
{
{
{
Based on consensus (Level C

recommendation by SORT)
Avoidance of vasoactive drugs
Conventional anti-migraine drugs
45
46

{
16 YOF was experiencing extreme jaw pain on

both sides of her face near the ears for at least a
few years, with worsening in past few months. On
occasions, the pain would radiate into the temples
and she would develop nausea and photophobia.
Also, she c/o non-painful clicking and popping in
both ears for 18 months. No traumatic history; no
systemic arthritic history
On exam, pain on reproduced upon mouth
opening, which was markedly limited. Lateral jaw
movement was also limited and there was
significant tenderness over both TMJ
47
TMJD (Costens syndrome)1

{
Group I: Muscle disorders

z
z
Group II: Disc displacement

z
z
II.a. Disc displacement with

reduction
II.b. Disc displacement without
reduction and no limitations in
aperture
II.c. Disc displacement without
reduction and with limitations in
aperture
Group III: Arthralgia, arthritis,

arthrosis
z
z
z
I.a. Myofascial pain

I.b. Myofascial pain with limitations
in aperture
III.a. Arthralgia
III.b. Osteoarthritis of the TMJ
III.c. Osteoarthrosis of the TMJ
Dworkin and LeResche, 1992
48
TMJD- epidemiological features

{
3-7% of the population

seeks treatment for pain
and/or dysfunction of the
TMJ or related structures1
Risk factors include:
z
z
z
z
z
Roda et al, 2007
Female gender
Increasing age
Systemic joint hyperlaxity
Bruxism
Psychosocial (stress,
anxiety)
From reference by Roda et al, 2007
49
TMJD- clinical manifestations

{
Local and referred pain

z
{
{
{
Ear, mandibular angle, parietal zone,

shoulder and face
Local and distant tenderness

Joint malfunction
Joint clicks
50
{
Mostly based on level B and C SORT

recommendations:
z
z
z
z
z
z
z
z
Nonsteroidal anti-inflammatory drugs

Corticosteroids
Muscle relaxants
Anxiolytics
Opioids
Tricyclic antidepressants
Topical capsaicin
Intraarticular injections (e.g., hyaluronic acid)
51
Nociceptive trigeminal inhibition

(NTI-tss)
{
FDA-approved for use in

migraine and tension-type
headache
Mechanism of action
believed to be related to
interruption of peripheral
sensitization processes
Effect suggested from low
grade studies and one
poorly designed, poorly
reported (Jadad= 1)
study*
*Source. Stapelmann and Turp 2008. Available at http://www.biomedcentral.com/content/pdf/14726831-8-22.pdf
52
53
Post-test
{
Referred pain can be explained by:

A.
B.
C.
D.
E.
Descending inhibition theory

Gating theory
Divergence theory
Convergence, hyperexcitability, and
neuron-glia signaling theories
Absence of cross communication
between various neuronal pools
54
Post-test
{
Examples of referred pain include:

A.
B.
C.
D.
E.
Migraine
Chest pain with abdominal distention
Forehead pain with giant cell arteritis
All of the above
A and C only
55
Post-test
{
Activation of nociceptors on posterior

inferior cerebellar artery branch of
vertebral artery are mostly felt in the
forehead region
56
Post-test
{
C-7 disc disease causes pain in the

ipsilateral forehead region
57
Post-test
Q5: Best match
1.
2.
3.
4.
5.
TMJ pain
Sensory nucleus of
cranial nerve V
Ophthalmic branch of
cranial nerve V
Basilar invagination
Pain with abdominal
distention
A.
B.
C.
D.
E.
Viscero-somatic
reflex
Cervicogenic
headache
Subnucleus oralis
Referred pain in face
and head
M1 segment of
middle cerebral
artery
58

Referred Pain

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Referred Pain

Uploaded by

Copyright:

Available Formats

Referred pain and headache

Nabih M Ramadan, MD, MBA

To discuss basic mechanisms of

Suggested mechanisms of referred pain

Examples of referred pain include:

Activation of nociceptors on posterior

Referred pain is conveyed from the

Illustrative case history #1

27 year old Caucasian lady presents with:

Episodic type I dizziness associated with left

Exam is normal except for marked tactile

Referred pain to the head

e.g. meninges, cerebral vasculature

e.g., trapezius, paraspinal muscles,

Mechanism: convergence theory

Afferent nerve fibers

Goadsby et al. Headache 2008

Mechanism: hyperexcitability theory

Cross connections between 2nd order neurons

Cardiac ischemia resulting in jaw pain

Activation of TNC via touch resulting in pain

Recent evidence for important

TG= trigeminal ganglion; TMJD= Temporo-mandibular joint disease

Sensory fibers that distribute with

Some neurons in all STNs

Neurons in TNC respond best

Manifestations, some examples

Cervical causes of headache

Headache with ischemic cerebrovascular

Temporo-mandibular joint disease (TMJD)

Illustrative case history #1

27 year old Caucasian lady presents with:

Episodic type I dizziness associated with left

Exam is normal except for marked tactile

Migraine associated vertigo

Not a fully accepted entity by IHS

Recurrent vestibular vertigo

Neuhauser HK et al, 2005, 2006, 2009

Reasons for association

Olivary-trigeminal reflex and/or connections

BRPV= Benign recurrent positional vertigo

Depends on the condition

Illustrative case history #2

38 YOF complained for about 5 years of

Chiari malformation types

Mildest form. Cerebellar tonsils displaced into

Most common form. Downward displacement of

Type II plus total cerebellar herniation through

Chiari malformation type-I (CMI)

Seen on ~0.5% of cranial MRI

Headache (most common)

Spinal cord signs and symptoms

Short lasting (<5 min), cough-headache

Headache fulfilling B-D and >1 of:

Precipitated by cough and/or Valsalva maneuver

Cerebellar tonsillar herniation on MRI:

>5 mm caudal descent of cerebellar tonsils

Compression of CSF spaces postero-lateral to

International Classification for Headache Disorders (ICHD), 2nd edition, 2004

Diagnostic criteria (continued)

D. Headache resolves within 3 months

Could be complicated by:

Illustrative case history #3