You are on page 1of 58

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
Q2: choose best answer
{

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
Q4 : True or false statements
{

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

Illustrative case #3

Temporo-mandibular joint disease (TMJD)


z

Illustrative case #4
20

21

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

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

Illustrative case history #2


{

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

Illustrative case history #3


{

{
{
{
{

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

Pharmacological management
{

{
{

Based on consensus (Level C


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

45

46

Illustrative case history #4


{

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

Pharmacological management
{

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
Q1: choose best answer
{

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
Q2: choose best answer
{

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
Q3 : True or false statements
{

Activation of nociceptors on posterior


inferior cerebellar artery branch of
vertebral artery are mostly felt in the
forehead region

56

Post-test
Q4 : True or false statements
{

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