TIC DOULOUREUX

AND

BILL SWEET, TOO.

WITH THANKS TO:

• John C. Liebeskind History of Pain Collection at Louise M. Darling Biomedical Library, UCLA

• Robert G. Ojemann• Washington State Historical Society• Many physicians

WILLIAM HERBERT SWEET

• Born January 13, 1910 in Kerriston, WA

• Lived in Rochester, MN 1917-1920• Seattle, WA 1920-1924 Graduated

from Broadway High School at age 14• Played piano for a year, worked in a

saw mill for a year, entered University of Washington

KERRISTON

Kerriston, WA c.1910

KERRISTON

Kerriston, WA c.1910

BROADWAY HIGH SCHOOL

Broadway High School c. 1924

WILLAIM HERBERT SWEET

• B.S. University of Washington 1930, summa cum laude, first in class of 1000

• Rhodes Scholar 1932-34

• B.Sc. Oxford University 1934

• A.T. Cabot Fellow, Harvard Medical School

1935-36

• M.D. Harvard University 1936, cum laude

UW

Denny Hall

• Neurosurgical House Officer, MGH 1936

• General Surgical House Officer 1936-37

• Neurological Resident Billings Hospital, Chicago 1937-38

• Neurosurgical Resident Billings Hospital, Chicago 1938-39

WILLIAM HERBERT SWEET

((Bucy, Bailey, and Walker)

WILLIAM HERBERT SWEET

• Neurosurgical Service, Radcliffe Infirmary, Oxford, and Rhodes Research Fellow National Hospital for Nervous Diseases 1939

• Instructor in Neurosurgery, Billings Hospital Chicago 1939-40

• Commonwealth Fund Fellow 1940-41

• Assistant in Neurosurgery, MGH 1940-41

WILLIAM HERBERT SWEET

• Acting Chief, Neurosurgical Service, Birmingham United Hospital, U.K. 1941-45

• Assistant in Neurosurgery, MGH 1945-47

• Instructor in Surgery, Harvard Medical School 1946-47

• Chief, Neurosurgical Service, MGH 1961-77

• Professor of Surgery, Harvard Medical School, 1965-1976

Barringer title

Birmingham

• Emeritus Professor of Surgery, Harvard Medical School 1976-2001

• D.H.C. Universite Scientifique et Medicale de Grenoble 1979

• F.R.C.S.Ed. (Hon) 1986

• D.Sc. Ohio State University 1993

WILLIAM HERBERT SWEET

Rogue River Neurosurgical SocietySWEET RANEY RAY RAFF MACK

Courtesy of Dr. William Buchheit

• King George VI Medal for Service in the Cause of Freedom 1945

• Emperor of Japan’s Order of the Rising Sun 1983

• Diplomate ABP&N 1946• Diplomate ABNS 1946• Phi Beta Kappa, Sigma Xi, Alpha Omega

Alpha

WILLIAM HERBERT SWEET

WILLIAM HERBERT SWEET

• Honored Guest of the Congress of Neurological Surgeons

• Cushing Medal of the American Association of Neurological Surgeons

• Distinguished Service Award of the Society of Neurological Surgeons

CLINICAL INTERESTS

• Boron Neutron Capture Theory• Treatment of Syndromes of Facial Pain• Treatment of Persistent Pain in General• Diagnosis and Treatment of

Craniopharyngiomas• Diagnosis and Treatment of Optic

GliomasMGH Website

Pain by White and Sweet

THE FOUR C’S OF GYBELS

• Competence• Creativity• Confidence• Courage

“All unostentatiously personified.”

“An inspiring role model, he was the most articulate

educator with whom I ever had the privilege of working.”

Gerald M. Aronoff

“Neurosurgery for him was a form of applied neuroscience rather than a

branch of surgery. No other neurosurgeon has contributed so much to the advancement of our

specialty…it was a privilege to have known him so well.”

B. Meyerson

“Some people look like scholars but are not, some are scholars but fall short in

their presentation; Sweet was a scholar, sounded like a scholar and was a

scholar in the classic sense. He was an unforgettable person. I knew him only in his later years, but memories of him

will be an inspiration for anyone looking into the abyss of aging.”

J. Campbell

‘“Hi, my name is William Sweet as in Sweet William.’ …gentle,

kindly and very supportive. In his leadership of APS he was

professional, rational, and, well, ‘sweet.’”

D. Chen

“He was a stalwart of the scholarly approach. Everything

about the pain business interested him. He was known for a

phenomenal memory.”

K. Burchiel

WILLIAM H. SWEET

TIC DOULOUREUX

SWEET ON TIC DOULOUREUX

White and Sweet 1969

CHARACTERISTICS OF TIC DOULOUREUX

• Intermittent, with pain-free intervals• Abrupt on and off• Lancinating, shock-like, stereotyped• Unilateral, trigeminal, rarely VII or IX• Minimal, if any sensory loss• Triggered by ipsilateral non-noxious

stimulation

TRIGGERING

• Response latency suggests large, myelinated afferents are involved.

• Often manifests refractory period if repetitively activated.

• Triggering site may be in a different division from pain site.

Anticonvulsants are the only class of medications that

control the pain of tic douloureux.

MEDICATIONS

• Phenytoin 100mg 300-600mg• Carbamazepine 100, 200mg 600-1800mg• Oxcarbamzepine 150, 300mg 800-1200mg• Baclofen 5, 10, 20mg 20-100mg• Gabapentin 100-800mg 900-4800mg

Generic drug Pill Size Dosing Range

SURGICAL TREATMENTS

• Neurectomy• Gangliolysis• Stereotaxic Radiosurgery• SOC with MVD• Trigeminal Rhizotomy• Trigeminal Tractotomy

GAMMA KNIFE TARGETTING

PAIN RELIEF: SURGERY FOR TIC

0

20

40

60

80

100

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

YEARS

PE

RC

EN

T

GANGLIOLYSIS

SOC + MVD

Tronnier results

Tronnier et al. 2001

MVMVDD

This study, and many others demonstrate that MVD does not

eliminate the pain of tic douloureux by damaging the

nerve.

TIC DOULOUREUXANATOMIC FINDINGS

• Demyelinization of trigeminal root and nerve

• Compression of trigeminal root

• Neoplasm of trigeminal nerve or root

MS Plaques

TIC DOULOUREUXPATHOPHYSIOLOGY

• Circus excitation in nerve and root

• Ectopic impulse generation• Ephaptic connections in nerve• Epileptiform disorder in

trigeminal nucleus

CIRCUS EXCITATION

• Impedance mis-match at branch points or regions of demyelination can result in reflected depolarization of the rapidly recovering segment.

• Could also occur if membrane channels were expressed that had different time constants.

Tigeminal anatomy White

and Sweet

White and Sweet 1969

ECTOPIC IMPULSE GENERATION

• Known to occur in damaged axons.

• Can originate in neuroma.

• Can occur in skin and ganglia adjacent to axon injury

• Can originate in dorsal root ganglion cells, perhaps in Gasserian Ganglion as well.

Ectopic impulse sites

Koltzenburg

Koltzenburg and Scadding 2001

EPHAPTIC CONNECTIONS

• Found in ventral roots of dystrophic rats.

• Never shown in a sensory system of any species.

• Since trigeminal nerve is somatotopically organized, should produce pain adjacent to triggering area, but this is often not the case.

EPILEPTIFORM FOCUS IN TRIGEMINAL NUCLEUS

• Epileptiform agents injected into trigeminal nucleus or dorsal horn of experimental animals produce a severe, constant pain state.

• Such pain is not obviously triggered, but it is eliminated by local anesthetic in

peripheral nerves.

DISCOVERING MECHANISMS:

THE PROBLEM

There is no animal model that has the characteristics

of tic douloureux.

Why is this type of pain syndrome seen only in cranial nerves? Tabes

dorsalis does produce a similar lancinating pain in spinal

segments. Spinal nerve root compression certainly does not.

CRITICAL QUESTION:

Is triggering a form of mechanical allodynia?

ALLODYNIA IN NEUROPATHIC PAIN

• Thought to indicate altered dorsal horn function.• Covers a wide area in a dermatome or nerve

territory.• Reported as burning.• May exhibit windup.• Alleviated by blocking involved nerve.• Not associated with a radicular mechanical lesion.

TRIGGERING IN TIC DOULOUREUX

• Not a diffuse dermatomal pattern.• Pain is not where stimulus is applied.• Often manifests refractory period, not

wind-up.• Pain reported as lancinating, not burning.• Is associated with possible axonal injury.

MOLECULAR GENETICS

Genetic factors can be shown to play a significant role in the

response to nerve injury in experimental animals. Thus far, no genetic factors have

been discovered in humans that are important in tic douloureux.

Genetic factors may also be the determinants of drug

efficacy and side effects in addition to their influence on susceptibility to the disease.

Is the variability in response to drug due to genetic differences of drug metabolism in those with tic,

or, alternatively, are there different mechanisms in patients

with a very similar clinical presentation?

GROWTH FACTORS

Axon damage may influence transport of growth factors to trigeminal nucleus, thereby

changing phenotype of sensory neurons.

DEVELOPMENT AND PLASTICITY

CYTOKINES

• Proinflammatory cytokines (IL-1B, TNF) are liberated at sites of nerve injury.

• Cytokines induce or increase pain behaviors that are associated with nerve injury.

• Relevance to tic is unknown.

Sprouting as a cause of neuropathic pain

Woolf Woolf 9999

PLASTICITY

The processes that initiate neuropathic pain may be different from those that

maintain it. Reduction of afferent input may change descending facilitation and

lead to chronic pain. Other forms of CNS reorganization may also occur.

Trigeminal tractotomy will stop the pain of tic douloureux;

therefore, the outflow of the trigeminal system to thalamus and

higher regions behaves as predicted and is like other pain

syndromes.

RECEPTORS

Absence of response to opioids suggests no role of c-fiber input

onto lamina II neurons in the genesis of tic pain; mu receptors have no influence on this pain syndrome. This supports the

concept of dorsal horn plasticity.

CHANNELS

Responsiveness to anticonvulsants suggests that changes in sodium channels

play a role in tic douloureux. Stereotypy of pain implies

damage to sub-set of axons in trigeminal system.

Up-regulation of a specific subset (Nav1.3/type III) of Na channels secondary to axonal injury may explain abnormal firing patterns

generated in mid-axon in response to an afferent volley.

Are there membrane channels in cranial sensory nerves that are

not found in other nerves elsewhere in the body?

Do they share a mechanism? Is it the same reason why

anticonvulsants are often effective?

Moving an artery away from the trigeminal root or damaging the

trigeminal nerve from its peripheral branches to the pons will stop

the pain of tic douloureux.

Physiological studies of the trigeminal nerve in humans

are difficult.

The mechanisms of tic douloureux will be discovered only through

animal experimentation.

TIC DOULOUREUX

An adequate standard of care does not include unrelieved tic pain. When medicines fail, surgery

should be promptly recommended.

TIC DOULOUREUX

THE MOST READILY CURED

CHRONIC PAIN SYNDROME

“Where does it hurt?” the dentist asked.

“In my mind,” thephilosopher replied. “Does anybody believe that a tooth is capable of hurting?”

BERTRAND RUSSELL VISITED THE DENTIST WITH

A TOOTHACHE

THANK YOU