This well written article for the layman was forwarded to me:
December 16, 2001, Sunday
MAGAZINE DESK
Pain, the Disease
By Melanie Thernstrom (NYT) 4579 words
A modern chronicler of hell might look to the lives of chronic-pain
patients for inspiration. Theirs is a special suffering, a separate
chamber, the dimensions of which materialize at the New England Medical
Center pain clinic in downtown Boston. Inside the cement tower, all
sights and sounds of the neighborhood -- the swans in the Public Garden,
the lanterns of Chinatown -- disappear, collapsing into a small
examining room in which there are only three things: the doctor, the
patient and pain. Of these, as the endless daily parade of desperation
and diagnoses makes evident, it is pain whose presence predominates.
''Yes, yes,'' sighs Dr. Daniel Carr, who is the clinic's medical
director. ''Some of my patients are on the border of human life. Chronic
pain is like water damage to a house -- if it goes on long enough, the
house collapses. By the time most patients make their way to a pain
clinic, it's very late.'' What the majority of doctors see in a
chronic-pain patient is an overwhelming, off-putting ruin: a ruined body
and a ruined life. It is Carr's job to rescue the crushed person
within, to locate the original source of pain -- the leak, the
structural instability -- and begin to rebuild: psychically,
psychologically, socially.
For leaders in the field like Carr, this year marks a critical
watershed. In January, the Joint Commission on Accreditation of
Healthcare Organizations, the basic national health care review board,
implemented the first national standards requiring pain assessment and
control in all hospitals and nursing homes. Standards for evaluating and
managing pain in lab animals have long been tightly regulated, but
curiously there had never before been any legal equivalent for people.
Maine took the further step last year of passing its own legislation
requiring the aggressive treatment of pain, and California and other
states are considering following suit.
''It's a field on the verge of an explosion,'' Carr says. ''There's no
area of medicine with more growth and more public interest. We've come
far enough scientifically to see how far we have to go.''
Chronic pain -- continuous pain lasting longer than six months --
afflicts an estimated 30 million to 50 million Americans, with social
costs in disability and lost productivity adding up to more than $100
billion annually. However, only in recent years has it become a focus of
research. There used to be no pain specialists because pain had always
been understood as a symptom of underlying disease: treat the disease
and the pain should take care of itself. Thus, specializing in pain made
no more sense than specializing in fever. Yet the actual experience of
patients frequently belied this assumption, for chronic pain often
outlives its original causes, worsens over time and appears to take on a
puzzling life of its own.
Research has begun to shed light on this: unlike ordinary or acute pain,
which is a function of a healthy nervous system, chronic pain resembles
a disease, a pathology of the nervous system that produces abnormal
changes in the brain and spinal cord. New technology, like functional
imaging, which is generating the first portraits of brains in action, is
revealing the nature of pain's pathology.
Far from being simply an unpleasant experience that people should endure
with a stiff upper lip, pain turns out to be harmful to the body. Pain
unleashes a cascade of negative hormones like cortisol that adversely
affect the immune system and kidney function. Patients treated with
morphine heal more quickly after surgery. A recent study suggests that
adequate cancer-pain treatment may influence the prospects for survival:
rats with tumors given morphine actually live longer than those that do
not receive it.
Paradigm shifts occur slowly; if arriving at a new medical conception of
pain has been difficult and protracted, disseminating the knowledge
will be more so. Pain treatment belongs primarily in the hands of
ordinary physicians, most of whom know little about it. Less than 1
percent of them have been trained as pain specialists, and medical
schools and textbooks give the subject very little attention. The
primary painkillers -- opiates, like OxyContin -- are widely feared,
misunderstood and underused. (A 1998 study of elderly women in nursing
homes with metastatic breast cancer found that only a quarter received
adequate pain treatment; one-quarter received no treatment at all.)
While the undertreatment of pain has led to lawsuits -- recently, a
California court issued a judgment against a Bay Area internist for
undertreating a terminally ill patient's cancer pain -- so has the
overprescribing of OxyContin in cases of patient abuse. It takes only a
few lawsuits -- along with the threat of Drug Enforcement Administration
oversight and regulation -- to exert a chilling effect on prescribing
practices. ''Doctors feel damned if they do and damned if they don't,''
says Dr. Scott Fishman, chief of the division of pain medicine at the
University of California at Davis Medical Center. ''The enormous
confusion about pain has led to the hysteria around opiates.''
Dr. James Mickle, a family doctor in rural Pennsylvania, describes the
leeriness most physicians feel about treating pain: ''Is it objective or
subjective? How do you know you're not being tricked or taken advantage
of to get narcotics? And chronic-pain patients are, generally, well -- a
pain. Most doctors' reaction to a patient with chronic pain is to try
to pass them off to someone who's sympathetic.''
And what makes a doctor sympathetic to pain?
''Someone who has pain himself,'' Mickle says. ''Or has an intellectual
interest -- who isn't interested in immediate results, doesn't want to
make money, has a lot of degrees. There's one in a lot of communities,
but then they get all the pain patients sent to them and eventually they
burn out and quit.''
Daniel Carr's interest in pain began as an intellectual one. After
training as an internist and endocrinologist, he published a landmark
study in 1981 of runners, which showed that exercise stimulates
beta-endorphin production, leading to a ''runner's high'' that
temporarily anesthetizes the runner. He began to wonder: if the runner's
high is an example of how a healthy body successfully modulates pain,
what abnormality leads to chronic pain? He did a third residency in
anesthesia and pain medicine, became a founder of the multidisciplinary
pain clinic at Massachusetts General Hospital and a director of the
American Pain Society. Six years ago, he moved to Tufts and set up a
pain clinic (which loses money) and created the country's first master's
program in pain for health professionals.
Every pain patient is a testament to the dangers of the conservative
wait-it-out approach to pain, as a day spent in Carr's clinic
demonstrates. But it is the last patient of the day, Lee Burke, whose
story proves the most instructive, because her diagnosis turns out to be
so simple, while the forces that worked against it being made earlier
were so complex.
Seven years ago, Burke -- a delicately featured 56-year-old woman in a
blue cotton sweater that picks up the blue of her eyes and the gray in
her hair -- learned she had one of the most survivable varieties of
brain tumors, a growth known as an acoustic neuroma behind her left ear.
The recovery period from the surgery to remove it was supposed to be a
mere seven weeks. Instead, she awoke from surgery with an unforeseen
problem. She had headaches -- lancinating lightning, hot pain -- that
knocked her out for periods ranging from four hours to four days. She
never returned to her job as an executive at a real-estate company. When
pain came between her and her husband, she left him -- and her money
and her home. ''It was easier to be alone with the pain,'' Burke says.
Carr asks her to describe the headaches. Like most of the 100-odd
patients I observed in various pain clinics trying to describe their
suffering, Burke seems stumped by the question. Therein lies a specific
damnation of pain. As Elaine Scarry writes in her seminal book, ''The
Body in Pain,'' pain is not a linguistic experience; it returns us to
''the world of cries and whispers.'' Patients grope at far-fetched
metaphors. ''A hot, banging pain, like an ice pick,'' says one. ''It
heats up and then sticks it in, again and again.''
Says Burke: ''It's like being slammed into a wall and totally destroyed.
It makes you want to pull every hair out of your head. There's nothing I
can do to defend myself.'' She looks at Carr with the particular
stricken bewilderment -- why and why me? -- that I saw on the faces of
so many pain patients. Pain, from the Latin word for punishment, poena,
can feel like the work of a torturer who must have -- but won't reveal
-- a purpose. ''It's like knives are going through my eyes,'' she says,
starting to weep.
While she blots her face, Carr sits calmly, his concentration fixed, his
hands folded reassuringly across his lap, with the equable, impersonal
kindness of a priest or a cop. Almost all of the patients during the
long day have broken down in their appointments. Perhaps because their
lives echo the chaos in his own blue-collar Irish-Catholic upbringing as
the son of an alcoholic bartender, he says, he isn't alarmed when
patients scream at him. He is neither indifferent to emotion nor
distracted by it; you sense at all times that his focus is on the
culprit -- the shape-shifter, the pain.
Carr asks Burke to close her eyes and taps her head with the corner of
an unopened alcohol wipe. Within a few minutes he has found a clear
pattern of numbness that suggests that one of the main nerves in her
face -- the occipital nerve -- was severed or damaged during her
surgery. It is clear from their differing expressions that Carr regards
this as revelation -- the demystification of her pain -- and that Burke
has no idea why.
Pain makes a child of everyone. Her voice becomes small as she asks, ''If the nerve was cut, why does it cause pain?''
It is a question researchers have only recently been able to answer.
Doctors used to be so confident that severed nerves could not transmit
pain -- they're severed! -- that nerve cutting was commonly prescribed
as a treatment for pain. But while cut motor nerves can be counted on to
cause paralysis, sensory nerves are tricky. Sometimes they stay dead,
causing only numbness. But sometimes they grow back irregularly or begin
firing spontaneously and produce stabbing, electrical or shooting
sensations.
Picture the pain wiring of the nervous system as an alarm, the body's
evolutionary warning system that protects it from tissue injury or
disease. Acute pain is like a properly working alarm system: the pain
proportionally matches the amount of damage, and it disappears when the
underlying problem does. Chronic pain is like a broken alarm: a wire is
cut and the entire system goes haywire. ''This is true pathology -- the
repair doesn't occur, because the system itself is damaged,'' explains
Clifford Woolf, an M.D.-Ph.D. pain researcher and the director of Mass.
General's neuroplasticity lab. It is called neuropathic pain because it
is a pathology of the nervous system.
Woolf was the first to answer an old puzzle: why does chronic pain often
worsen over time? Why doesn't the body develop tolerance? Woolf's
research demonstrated that physical pain changes the body in the same
way that emotional loss watermarks the soul. The body's pain system is
plastic and therefore can be molded by pain to cause, yes, more pain. An
oft-used metaphor is that of an alarm continually reset to be more
sensitive: first it is triggered by a cat, then a breeze and then for no
reason it begins to ring randomly or continuously. As recent research
by Allan Basbaum at the University of California at San Francisco has
shown, with prolonged injury progressively deeper levels of pain cells
in the spinal cord are activated. Pain nerves recruit others in a
''chronic-pain windup,'' and the whole central nervous system revs up
and undergoes what Woolf calls ''central sensitization.''
Lee Burke's records do not even note whether her occipital nerve was
cut, and her surgeon may not have noticed the dental-floss-size nerve.
It took more than a year of complaints before she was referred to Dr.
Martin Acquadro, the director of cancer pain at Mass. General, who noted
that she had severe muscle spasms in her head, neck and shoulders. It
was a classic pain misinterpretation: he seized on muscular pain as the
primary problem, rather than a secondary symptom, and diagnosed tension
headaches.
He treated her with Botox injections, tricyclic antidepressants and
migraine medications. She tried range-of-motion physical therapy,
stress-reduction courses, psychiatric treatment, yoga and meditation and
consumed 3,200 milligrams of ibuprofen a day, along with 12 cups of
coffee (caffeine is a treatment for migraines). He steered her away from
opiates with warnings about their addictive qualities.
Until recently, opiates were the only serious pain drug available. But
neuropathic pain is the kind of pain for which opiates are the least
effective. In the past few years, however, an alternative has come
along. A new antiseizure drug, Neurontin, has been found to also act as a
nerve stabilizer that can quiet the misfiring nerves responsible for
neuropathic pain.
When I call her four months after the appointment with Carr, Burke says
she feels 50 percent better from a combination of Neurontin and other
drugs. The muscle spasms -- so rigid that Acquadro compared them to
railroad tracks -- had melted. She no longer needed a snorkel for her
daily swim because she could move her head from side to side again. Of
course, you have to be in terrible pain to find the side effects of pain
drugs tolerable. But while her headaches sometimes required so much
Neurontin that she was too dazed to walk, she was glad to be able to sit
up to watch television instead of simply lying prone in agony.
''Dr. Carr is my savior,'' she says. I recall the way she left the
appointment, clasping his hand as if she wanted to kiss it and looking
at him with hope so intense it was hard to watch.
''There's tremendous ignorance about neuropathic pain,'' Woolf says.
''Most doctors don't know to look for it.'' One confusing factor is that
not all patients with similar conditions develop chronic pain.
Neuropathic pain seems to require genetic vulnerability. Pain clinics
are filled with patients with ordinary conditions and extraordinary
pain. M.R.I.'s show only bones and tissue; doctors might look at a
patient's scan and say, ''Your back looks fine -- the muscle swelling is
gone'' or ''The bone's all healed,'' and conclude there is no reason
for pain. But the pain is not in the muscles or bones; it is in the
invisible hydra of the nerves.
Of course, not all chronic pain is neuropathic -- there is inflammatory
pain, for example, or muscular pain. But many chronic-pain conditions,
like backache, which was once assumed to be wholly musculoskeletal, are
now thought to have a neuropathic component.
About 10 percent of women used to complain of chronic pain following
radical mastectomies. Their pain had always been interpreted as a
psychological phenomenon: they were just ''missing'' their breasts. But
in the early 1980's, Dr. Kathleen Foley at Memorial Sloan-Kettering
Cancer Center in New York identified the pain as being caused by the
severing of a major thoracic nerve during surgery, and the technique was
revised.
Doctors warn patients of many risks, from death to scarring, but rarely
mention the not-uncommon side effect of chronic pain. The life of one of
Carr's patients was ruined by having a nerve nicked during plastic
surgery to correct protruding ears. Another acquired chronic chest pain
after being treated in a hospital for a collapsed lung when a tube was
inserted in her chest -- one of the most nerve-rich areas in the body.
One especially poignant category of patients in pain clinics is that of
those who have had surgery specifically to treat chronic -- usually back
-- pain where the surgery leads to new, worse pain, an outcome for
which they say they had no warning.
Pain doctors have many theories about why these kinds of things happen,
but the dialogue is frustratingly one-sided. There are no spokesmen for
undertreating pain -- no one advocates not treating pain.
Although I contacted many of the former doctors of pain patients, it was
rare that one was willing to examine his decisions thoughtfully, as
Martin Acquadro did. It was immediately clear to me that Acquadro, a
licensed dentist as well as an anesthesiologist, was both competent and
caring and that the forces that delayed Burke's treatment were not
personal shortcomings but genuine, pervasive confusions about pain.
Acquadro thought the pain of all acoustic neuroma patients should
manifest itself similarly, and most of those he had seen did, in fact,
''respond to simpler, more holistic therapies.'' He had not thought of
Neurontin, and he feared opiates. ''We don't always do patients a favor
putting them on high-dose narcotics,'' he says. ''When a patient is
depressed or anxious, you're leery about narcotics or alcohol. With Lee,
I guess I'd have to say I was being cautious.'' His voice changes --
softens and quiets -- as he gets to the real point: ''I was afraid.''
Like many doctors, he says he felt comfortable with anti-inflammatory
drugs, although the 3,200 milligrams of ibuprofen that Burke took daily
put her at risk for gastrointestinal bleeding. According to the Federal
Drug Abuse Warning Network, anti-inflammatory drugs (including aspirin
and Aleve) were implicated in the deaths of 16,000 people in 2000
because of bleeding ulcers and related complications. While large doses
of the drugs are sometimes needed to treat inflammation, opiates are a
much safer -- and generally more effective -- analgesic.
Although far fewer than 1 percent of pain patients using opiates develop
any addictive behavior, opiates have a reputation for being dangerous,
and social biases -- class, race and sex -- influence who is entrusted
with them. Studies by Dr. Richard Payne at Sloan-Kettering show that
minorities are up to three times as likely as others to receive
inadequate pain relief -- and to have their requests for medication
interpreted as bad ''drug-seeking behavior.'' A study conducted by Dr.
William Breitbart at Sloan-Kettering found that women with H.I.V. are
twice as likely to be undertreated for pain as men. Many of Carr's
patients have some social strike against them that led their previous
doctors to withhold treatment: two were workers' compensation cases, one
was mentally ill, several had histories of substance abuse, all of them
were poor and most were women.
Women tend to be either less aggressive in demanding pain treatment or
to be aggressive in ways that are misinterpreted as hysteria. The longer
pain goes untreated, the more desperate and crazed the patient becomes
-- until those behaviors look like the problem. Burke recalls that
whenever Acquadro sent her to other specialists -- headache specialists,
balance specialists and behavioral pain-medicine specialists -- she
would break down during the appointments in pain and frustration. ''They
all just figured I was a basket case,'' she says. ''And I was. I was a
basket case.''
Rather than dismiss her psychic distress, Acquadro seems to have become
overly focused on it, trying to explain her pain through that prism:
''Lee's pain seemed to be better at the times she was happier, was
forming new relationships or helping others,'' he says. ''And even
though she was motivated and worked hard on stress reduction, the fact
remains, she is a tense person.''
Naturally. Everyone who has chronic pain eventually develops anxiety and
depression. Anxiety and depression are not merely cognitive responses
to pain; they are physiologic consequences of it. Pain and depression
share neural circuitry. The hormones that modulate a healthy brain, like
serotonin and endorphins, are the same ones that modulate depression.
Functional-imaging scans reveal similar disturbances in brain chemistry
in both chronic pain and depression.
''Chronic pain uses up serotonin like a car running out of gas,'' says
Breitbart. ''If the pain persists long enough, everybody runs out of
gas.'' Thus, Acquadro's not treating Burke's pain aggressively because
she was ''tense'' is like ''not rescuing someone who is drowning because
they're having a panic attack,'' according to Breitbart. Difficulty
breathing triggers panic as reliably as pain causes depression. When
serotonin is inhibited in laboratory animals, morphine ceases to have an
analgesic effect on them. Medications that treat depression also treat
pain. Depression or stressful events can in turn enhance pain. Since
Sept. 11, pain clinics have been fuller. ''If we started putting sugar
in the water, it would affect the diabetics first -- pain patients
respond to stress with increased pain,'' explains Scott Fishman, who
also trained as a psychiatrist. But to make stress reduction a primary
strategy for pain treatment is trying to repaint the walls of a
crumbling house.
It is an easy mistake to make -- and one I made myself. i developed pain
five years ago for, what seemed to me, absolutely no reason. A fiery
sensation flared in my neck, flowed through my right shoulder and
sizzled in my hand. It didn't feel like normal pain -- it felt like a
demon had rested a hand on my shoulder. Suddenly I tasted brimstone and
burning.
Two years later, an M.R.I. would reveal spinal stenosis, a narrowing of
the spinal canal, and cervical spondylosis, a type of arthritis, both of
which squeeze the nerves and cause pain to radiate into my shoulder and
hand. But in the meantime, I was convinced that if I steadfastly
ignored it, the pain would eventually go its own way. I tried to treat
it as a psychological problem. Many pain patients have had doctors who
pathologized them, told them their pain was unreal; I pathologized
myself, hoping my pain was unreal -- or that it would become so if I
treated it as such.
I analyzed the pain in psychotherapy. I tried acupuncture, massage and
herbal remedies. I read books about conversion hysteria, the placebo
effect and Sufis who thread fishhooks through their pectoral muscles.
What I didn't read was anything that might have actually informed me
about my symptoms, like Fishman's excellent patient-oriented book, ''The
War on Pain.'' Nor did I consult any clarifying Web sites, like
painfoundation.org.
When the pain depressed me, I focused on the depression. I adopted Dr.
John E. Sarno's popular creed that muscular tension syndrome is the
source of most back ills and faithfully scrutinized my life for stress.
It is one of those circular self-confirming hypotheses: when I was happy
and my pain light, I took it as confirmation of the correlation; when I
was happy but had a lot of pain, I wondered if I didn't want to be
happy. I recall how, strapped inside the white crypt of the M.R.I.
machine for more than an hour, I tried to calm myself by repeating the
motto of my Christian Scientist grandparents: ''There is no life, truth,
intelligence nor substance in matter. All is infinite Mind and its
infinite manifestation.'' But I sensed the machine was seeing my pain in
its own way and that its report would be irrefutable. My pain would no
longer be a tree falling in the forest with no one to hear it. The
greatest fear pain patients have, doctors sometimes say, is that it is
''all in their heads.'' But infinitely scarier, I thought as I lay
there, is the fear that it isn't.
His is the new frontier of medicine,'' Clifford Woolf says heatedly in
his clipped South African accent. ''What we're learning is that chronic
pain is not just a sensory or affective or cognitive state. It's a
biologic disease afflicting millions of people. We're not on the verge
of curing cancer or heart disease, but we are closing in on pain. Very
soon, I believe, there will be effective treatment for pain because, for
the first time in history, the tools are coming together to understand
and treat it.''
The most important tool in his lab at Mass. General -- a vast landscape
of test tubes filled with rat DNA -- is the new ''gene chip'' technology
that identifies which genes become active when neurons respond to pain.
''In the past 30 years of pain research, we've looked for pain-related
genes, one at a time, and come up with 60. In the past year, using
gene-chip technology, we've come up with 1,500,'' Woolf says happily.
''We're drowning in new information. All we have to do is read it all --
to prioritize, to find the key gene, the master switch that drives
others.''
Woolf is particularly interested in certain abnormal sodium ion channels
that are only expressed in sensory neurons that have been damaged. He
believes he is close -- perhaps a year away -- from identifying which
among these channels is the most important one. Then -- if his animal
data applies to humans -- pharmaceutical companies could design blockers
for these channels, and after the years it takes to develop a new drug,
there could be a cure for neuropathic pain.
On the table before us in Woolf's lab, a graduate student is piercing
the sciatic nerve of a white rat. The rat is of a pain-sensitive
variety, one prone to developing neuropathic pain. In 10 days, when
Woolf cuts open the rat's brain, he will be able to discern the imprint
of the sciatic nerve injury. There will be corresponding maladaptive
changes in the way the brain processes and generates pain.
The biggest question of pain research is whether this pathological
cortical reorganization can be undone. A 1997 University of Toronto
study has shown disturbing implications. Anna Taddio compared the pain
responses of groups of infant boys who had been circumcised with and
without anesthesia. Four to six months later, the latter group had a
lowered pain threshold, crying more at their first inoculations --
providing evidence that there is cellular pain memory of damage to the
immature nervous system.
Terms like ''pathological cortical reorganization'' and ''cellular pain
memory'' have a very ominous ring. Are these children really doomed to
be more sensitive to pain their entire lives? Will a cure for
neuropathic pain help all the people who already have it -- or only
prevent others from developing it?
Woolf looks at me and hesitates. ''We don't really know,'' he says
tactfully. Another pause. ''In the present state, no.'' However, he
says, even if the damage cannot be undone, treatment could still help
suppress the abnormal sensitivity. ''But obviously, it's going to be
much easier to prevent the establishment of abnormal channels than to
treat the ones already there.'' He sighs, rests his head against his
hand. ''Obviously.''
I want to ask another question, but I'm overcome by a rare unreporterly desire. I want him to get back to work.
C@ 2002 NYT
http://www.bayareapainmedical.com/wwhatshot.html
- Good Site -
Bay
Area Pain Medical Associates welcomes physicians and other health care
professionals to this section of the website. Although it is open to anyone to
browse, the information is oriented towards physicians interested in developing
and attaining up to date information in pain medicine.
http://www.rsdrx.com/CRPSABSTRACT.htm
- Article -
Neurological Associates Pain Management Center
- Interesting site CRPS-RSD links? - again don't agree 100% with the
pharmacology discussed. http://www.rsdrx.com/rsdtext_book.htm
- RSD lessons?
Hooshang Hooshmand, M.D. and Masood
Hashmi, M.D.
Neurological Associates Pain Management
Center
903 East Causeway Blvd. Vero Beach, FL
32963
|
***
Summarized from the review article
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Complex
Regional Pain Syndrome-
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Reflex Sympathetic
Dystrophy Syndrome:
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( Pain Digest-
1999; 9:1-24)
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http://pedsanesthesia.stanford.edu/guide/guideline-unconvent.html-
Good discussion on Pain Management (note: Pediatric dosages)
Uncoventional Analgesics for Pediatric Pain
Management©
MEMBRANE STABILIZERS:
Intravenous
Lidocaine
Lidocaine
is beneficial in the treatment of neuropathic pain states by blocking
conduction of sodium channels in peripheral and central neurons, and
therefore reducing spontaneous impulse firing.(i,ii)
Furthermore, the effectiveness of intravenous lidocaine (IVL) in
producing analgesia is a predictor of the subsequent efficacy of oral
mexiletine both in the treatment of cardiac arrhythmias (iii)
and in the treatment of neuropathic pain.(iv)
Although animal studies have shown that intravenous lidocaine
alleviates tactile allodynia in rats (v),
human studies have found no association between reduction in allodynia
and pain relief.(iv)
Typically, IVL is administered to a target plasma lidocaine level
of 2-5 µg/ml.(vi,vii,viii)
There
are few reports of the use of lidocaine for treatment of neuropathic
pain states in children. Wallace
and others (ix)
used intravenous lidocaine to control pain after anti-GD2 antibody
therapy in children with neuroblastoma using IVL at 2 mg/kg over 30
minutes followed by 1 mg/kg/hr. Compared
with a morphine infusion (0.05-0.1 mg/kg/hr), lidocaine was associated
with improved mobility and decreased supplemental analgesic
requirements. Of note,
extended use of lidocaine infusions over 4 days was associated with an
increased incidence of nausea.
Our
clinical experience confirms that lidocaine is useful for treatment of
pediatric neuropathic conditions. We
routinely employ lidocaine as an adjunct medication for pain syndromes
refractory to conventional therapy, such as the pain of mucositis
following bone marrow transplantation and refractory cancer pain
(x,xi),
and also in neuropathic pain states such as CRPS-1, CRPS-2,
erythromelalgia, and painful neuropathies to predict the efficacy of
mexiletine (see below).
Because
lidocaine pharmacokinetics are similar in children and adults, dosing
schedules for children should correlate reasonably with published
experience in adults. Lidocaine
plasma levels are readily available in most clinical laboratories, to
assure that infusions are delivering an effective dose without producing
toxicity. The most accurate way to deliver intravenous lidocaine is by a
computerized infusion, a technique utilized in our adult pain clinic, in
which our protocol calls for an initiating bolus of lidocaine equal to 1
mg/kg over 5 minutes, with subsequent infusion of lidocaine at a rate of
1 mg/kg/hr. Blood levels
are checked every 8 hours and the lidocaine infusion is adjusted to
target a blood level between 2-5 µg/ml.
Patients with hepatic or renal insufficiency need dose
adjustments (halving the dosage of bolus or infusion) to prevent
toxicity.
Mexiletine
Originally
used as an oral cardiac antiarrhythmic analog of lidocaine, mexiletine
is used by most pain treatment centers as an oral analog to lidocaine to
treat neuropathic pain. The
original antiarrhythmic studies for lidocaine showed that it was a
useful predictor for the antiarrhythmic efficacy of mexiletine and
tocainide. Tocainide,
unfortunately, produces significant toxicity such as blood dyscrasias
and interstitial pneumonitis. Mexiletine,
on the other hand, is without such toxicity and is much better
tolerated. Dejgard and
others (xii)
reported a dose of mexiletine of up to 10 mg/kg daily to treat diabetic
neuropathy. Mexiletine was
used with at similar doses by Chabal and others in adults to treat
peripheral nerve injuries.(xiii)
Chabal commented that most subjects required a daily dose of
mexiletine of 10 mg/kg for pain, while the usual range for treatment of
cardiac arrhythmias is between 10-15 mg/kg.
A
review of the pediatric literature shows no pharmacologic or
pharmacokinetic difference in the absorption or metabolism of mexiletine
between children and adults. Mexiletine
is frequently associated with untoward gastrointestinal side effects,
most commonly nausea and vomiting, as well as sedation, confusion,
difficulty concentrating, diploplia, blurred vision, and ataxia,
although gradual introduction of the drug and progressive escalation of
the dose is ordinarily successful in reducing this side effect, as
illustrated in Table 1.
Table
1.
Mexiletine dosing
schedule for children. Mexiletine
is available as 150mg, 200mg, 250mg, and 300mg tablets.
The target dose is 10-15 mg/kg.(xiv)
|
DAY
|
Morning
|
Mid-day
|
Bed-time
|
|
1
|
|
|
1
Tablet
|
|
2
|
|
|
1
Tablet
|
|
3
|
|
|
1
Tablet
|
|
4
|
1
Tablet
|
|
1
Tablet
|
|
5
|
1
Tablet
|
|
1
Tablet
|
|
6
|
1
Tablet
|
|
1
Tablet
|
|
7
|
1
Tablet
|
1
Tablet
|
1
Tablet
|
|
8
|
1
Tablet
|
1
Tablet
|
1
Tablet
|
|
9
|
1
Tablet
|
1
Tablet
|
1
Tablet
|
|
10
|
1
Tablet
|
1
Tablet
|
2
Tablets
|
|
11
|
1
Tablet
|
1
Tablet
|
2
Tablets
|
|
12
|
1
Tablet
|
1
Tablet
|
2
Tablets
|
|
13
|
1
Tablet
|
1
Tablet
|
2
Tablets
|
|
14
|
2
Tablets
|
1
Tablet
|
2
Tablets
|
|
15
|
2
Tablets
|
1
Tablet
|
2
Tablets
|
|
16
|
2
Tablets
|
1
Tablet
|
2
Tablets
|
|
17
|
2
Tablets
|
1
Tablet
|
2
Tablets
|
|
18+
|
2
Tablets
|
2
Tablets
|
2
Tablets
|
ANTICONVULSANTS
Carbamazepine
(Tegretol®)
Carbamazepine
is an older anti-epileptic used to treat neuropathic pain via sodium
channel blockade. Carbamazepine can be administered in oral
(100-200 mg) and suspension formulations (100 mg/5 ml).
Recommended dosing schedules for children > 6 years start at 10
mg/kg/day in two divided doses to a usual maintenance dose of 15-30
mg/kg/day in 2-4 divided doses per day. Blood levels (therapeutic
4-12 mcg/ml) can be obtained but do not necessarily correlate with
analgesia for neuropathic pain.
Metabolism
and adverse effects are significant with carbamazepine.
Carbamazepine is hepatically metabolized, limiting its usefulness
patients with hepatic insufficiency. Moreover, adverse effects are
common including hematologic – aplastic anemia, agranulocytosis;
cardiovascular – congestive heart failure, syncope, arrhythmias;
central nervous system – sedation, dizziness, fatigue, slurred speech,
ataxia; and even hepatitis.(xv) A complete blood count should be
obtained prior to initiating this antiepileptic and should be repeated
every 3-6 months. Although a classic agent for the management of
neuropathic pain, carbamazepine is no longer a first line drug,
particularly for a child or adult who may have hematologic alterations
or hepatic dysfunction.
Sodium
Valproate (Depakote®)
Valproic
acid is an anti-epileptic drug that has been used to treat neuropathic
pain states and associated mood disturbances. The drug also seems
effective for management of migraine headaches, but because of
significant side effects, valproate is not usually a first-line agent.
The
mechanism of action for valproate is unclear. The drug has a wide
spectrum of anticonvulsant applications, therefore multiple mechanisms
of action are proposed. Loscher describes at least three
mechanisms.(xvi) Valproate increases GABA synthesis and release,
which may partially explain efficacy in treating central pain.
Valproate also attenuates neuronal excitation induced by NMDA-type
glutamate receptors. NMDA receptors have some correlation with
centralization of neuropathic pain states or the “wind-up”
phenomenon. Moreover, valproate has direct effects on excitable
membranes and acts as a membrane stabilizer, similar to intravenous
lidocaine and mexiletine.
Valproate
is available in an oral tablet, syrup, and rectal suppository.
Dosing starts at 10-15 mg/kg/day to a maximum of 30-60 mg/kg/day.
The drug has a half-life in children of 6-18 hours with a peak effect in
4 hours after administration. Plasma concentration does not
correlate with toxicity, seizure control, or analgesia. Valproate
is protein-bound (80-95%) and metabolized by glucuronidation and other
oxidative pathways.
Adverse
effects can be significant. Typical toxic effects within the first
several months include anorexia, nausea/vomiting, sedation, and weight
gain or loss. Valproate may cause hepatotoxicity and hepatic
dysfunction in 5-30% of patients. Other less common adverse
effects include hyperammonemia, pancreatitis, and platelet dysfunction.
For these reasons, valproate is not a first-line agent. Liver
function tests should be performed prior to initiation of valproate
treatment and then every month for the next 6 months. Symptoms
such as malaise, lethargy, gastrointestinal symptoms, and easy bruising
may indicate liver dysfunction and lead to immediate laboratory
evaluation and discontinuation of the drug. (xvii)
Gabapentin
(Neurontin®)
Gabapentin
is a compound that was originally synthesized as a gaba-ergic drug to
treat spasticity. It was
later
found to be more effective as a potent anticonvulsant for treating
partial seizures and generalized tonic-clonic seizures.(xviii,xix)
At this time, the mechanism of action of this agent is unclear.
Gabapentin may enhance extracellular GABA levels by reversing
GABA transport in a unique way. The
compound does not reduce voltage sensitive sodium channels or affect
NMDA receptors. On a
biochemical level, gabapentin may inhibit a branched chain amino acid
transferase ultimately producing a decreased level of glutamate, an
excitatory amino acid that may be important in nerve transmission.
Increased activity of glutamate dehydrogenase and glutamic acid
decarboxylase has also been noted in gabapentin treated animals, further
decreasing levels of glutamate.
The
most remarkable clinical feature of gabapentin is its few and infrequent
side-effects or dose limiting factors.
In fact, it is safe to say that of the many agents described in
this chapter for the management of pain, none has a more benign side
effect or toxicity profile.
Gabapentin
is not protein bound; therefore, distribution is not affected by
alterations in hepatic function. Gabapentin
is not metabolized, and therefore does not induce hepatic enzymes.
Gabapentin elimination is entirely by renal excretion.
Dosage must therefore be adjusted proportionally to the reduction
in creatinine clearance.
Side
effects are predominately limited to the central nervous system:
somnolence, dizziness, ataxia, nystagmus and tremor.
These effects are dose related and are usually minor.
Dosage
for adults ranges from 300 mg/day to 5600 mg/day.
Gabapentin has a biological half-life of 5-9 hours and therefore
is typically prescribed on a three times a day schedule.
Higher dosages (for example, >20 mg/kg/day) require more
frequent administration because gastrointestinal absorption depends upon
an L-amino acid transporter in the gastrointestinal tract that may
become saturated at higher gabapentin dosages, producing diarrhea.
The
use of gabapentin has been well described in the pediatric literature,
using doses from 5-30 mg/kg for the management of seizure disorders.(xx,xxi)
Behavioral side effects of gabapentin have been described in
children consisting of intensification of baseline behaviors including
tantrums, hyperactivity, oppositional behavior, fighting, and increased
anger.(xxii)
A disinhibition theory similar to one seen with benzodiazepine
therapy has been postulated as the cause.
Gabapentin
has been unambiguously found to be beneficial in treating chronic
neuropathic pain syndromes in adults.
Mellick (xxiii)
described the use of gabapentin in complex regional pain syndrome type
I, in which significant pain relief and possible reversal of the disease
process was found. Controlled
studies by Robotham (xxiv)
for postherpetic neuralgia and Backonja (xxv)
for neuropathy secondary to diabetes mellitus also suggest efficacy of
treatment in these neuropathic pain conditions.
Backonja additionally found that gabapentin therapy had a
positive effect on mood.
In
the treatment of pain in the pediatric population, reports are few,
limited mostly to case reports and small series. (xxvi) Since the
initiation of use of gabapentin, however, its clinical utility has far
outpaced the published data. In part, this may be due to the
relative paucity of agents useful in neuropathic pain, and the
significant side effects of these agents. In our clinic,
gabapentin is frequently used as a first or second line agent for the
treatment of neuropathic pain, initially at 10mg/kg and gradually
escalating over several weeks to a maximum of 50mg/kg. The daily
dosage may be titrated up to 70 mg/kg/day depending on clinical response
and side effects. (xxvii)
TRICYCLIC ANTIDEPRESSANTS
Depression
and other psychological symptoms such as anxiety and anger accompany
many chronic pain conditions. Originally,
chronic pain patients were treated for depression and coincidentally
found significant pain relief independent of the mood altering affect of
antidepressant medication. Subsequent
studies by Max (xxviii)
and others (xxix,xxx)
showed statistically significant relief in treating neuropathic pain
syndromes.
Antidepressants
therefore have multiple uses in pain medicine.
These agents are used to treat depression, anxiety, sleep
disturbance, and, of course, pain.
All
tricyclic antidepressants that have been tested have equal efficacy at
therapeutic dosages. While
most antidepressants take 4-6 weeks to reach their full antidepressant
effect, the onset of analgesic effect is less clear, but is almost
certainly much shorter than that for the antidepressant effect.
The
pharmacology of tricyclic antidepressants is well defined.
The mechanism of action of tricyclic antidepressants is the
reuptake inhibition of serotonin and norepinephrine from synaptic
junctions in the central nervous system.
Each TCA has varying degrees of effect on serotonin and
norepinephrine levels, depending upon whether the drug is a primary or
tertiary amine.
Tricyclic
antidepressants have a high first pass metabolism by the liver after
absorption from the gastrointestinal tract.
They are highly protein bound in plasma to alpha-1 acid
glycoprotein. Tricyclic
antidepressants are lipophilic molecules, therefore accumulate in the
body’s fat stores; biologic half-lives are quite long (1-4 days).
In
patients, there is wide plasma TCA level variability due to genetic
polymorphism. TCAs are
metabolized by P450 2D6. The
biochemical activity of the drug metabolizing isozyme cytochrome P450
2D6 (debrisoquin hydroxylase) is reduced in a subset of the Caucasian
population (about 7-10% of Caucasians are so called "poor
metabolizers"); reliable estimates of the prevalence of reduced
P450 2D6 isozyme activity among Asian, African and other populations are
not yet available. Poor metabolizers have higher than expected plasma
concentrations of tricyclic antidepressants when given usual doses.
Depending on the fraction of drug metabolized by P450 2D6, the increase
in plasma concentration may be small, or quite large (8-fold increase in
plasma level of the TCA).
In
addition, certain drugs inhibit the activity of this isozyme and make
normal metabolizers resemble poor metabolizers. An individual who is
stable on a given dose of TCA may become abruptly toxic when given one
of these inhibiting drugs as concomitant therapy. The drugs that inhibit
cytochrome P450 2D6 include some that are not metabolized by the enzyme
(quinidine; cimetidine) and many that are substrates for P450 2D6 (many
other antidepressants, phenothiazines, and the type 1C antiarrhythmics
propafenone and flecainide). While
all the selective serotonin reuptake inhibitors (SSRIs), e.g.,
fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary
in the extent of inhibition. The extent to which SSRI-TCA interactions
may pose clinical problems will depend on the degree of inhibition and
the pharmacokinetics of the SSRI involved. Nevertheless, caution is
indicated in the coadministration of TCAs with any of the SSRIs and in
switching from one class to the other. Of particular importance,
sufficient time must elapse before initiating TCA treatment in a patient
being withdrawn from fluoxetine, given the long half-life of the parent
and active metabolite (at least 5 weeks may be necessary).
Typical
side effects of TCAs are dose-related and include:
-
Antihistaminic
(H1 and H2): sedation and increased gastric pH
-
Antimuscarinic:
dry mouth (xerostomia), impaired visual accommodation, urinary
retention, and constipation
-
Alpha-adrenergic
blockade: orthostatic hypotension
-
Appetite
stimulation: weight gain
-
Quinidine-like
effect: QRS widening, prolonged QTc. As early as 1990 in
“The Medical Letter” and as recently as 1997, reports of the
sudden death of children have raised concerns of life threatening
arrhythmias.(xxxi,xxxii) Sudden deaths in TCA-treated children
may be idiosyncratic. Desipramine and imipramine in particular seem
to produce greater changes in baseline EKG, specifically increased
QRS duration.
Amitriptyline
(Elavil®)
Collins
(xxxiii)
retrospectively described eight children, ages 5-17 years, in whom
intravenous amitriptyline was effective in treating neuropathic pain,
depression, sleep disturbance, and as an adjuvant for opioid analgesia.
The calculation of initial intravenous dosage for
‘amitriptyline naïve” children was 0.2mg/kg/day, with ultimate
doses of 0.05-2.4 mg/kg/day given intravenously.
Side effects in addition to those listed above included dysphoria,
which might have been secondary to concurrent opioids, and
extrapyramidal effects that resolved with diphenhydramine.
While
children may be rapid metabolizers of amitriptyline, and therefore
require twice-daily dosing schedule, a single daily dose is usually
first used until a side effect profile is established for individual
patients. The most
prominent and consistent side effect is somnolence; therefore, the daily
dose is generally given before bedtime.
A recommended initial dosage is 0.05 mg/kg/day, escalating over a
period of 3-4 weeks to approximately 0.5-1 mg/kg/day is generally
sufficient for pain management, although higher doses have been used in
the past for mood elevation. Amitriptyline may also be parenterally
administered as an intramuscular injection using about one-third to
one-half the oral dose. The
intramuscular preparation presently marketed may also be administered
intravenously over a period of 2 hours, to mimic the absorption of an
intramuscular injection.
The
utility of routine measurement of plasma drug levels in pain management
is dubious, because no correlation has been shown between plasma drug
levels and analgesia. However,
plasma levels may identify a rapid or slow metabolizer, confirm
patient/parent compliance with prescription, and optimization of dosage
prior to discontinuation of trial.(xxxiv)
Nortriptyline
(Pamelor®)
Nortriptyline
is a compound with virtually identical pharmacology to amitriptyline,
but because of the demethylation of the terminal amide group, the side
effect profile is superior to amitriptyline, particularly in regards to
its sedative and antimuscarinic effects.
While
published experience with nortriptyline is lacking in pediatrics,
experience shows that it is equally effective, and preferable when
daytime somnolence limits the use of amitriptyline.
Desiprimine
(Norpramin®)
Desipramine
has been reported to be associated with sudden death in several
pediatric cases; therefore, its use has been abandoned for the
management of pain in children.
Selective Serotonin Reuptake
Inhibitors (SSRI's)
While
most useful to treat clinical signs of depression complicating the
management of chronic pain, most SSRIs are less effective as specific
analgesics than TCAs, although Sindrup, et al. found some benefit in
using paroxetine (Paxil®) to treat diabetic neuropathies, especially
when patients could not tolerate the side-effects of tricyclic
antidepressants.(xxxv)
The notable exception to the absence of analgesic properties with
this newest class of antidepressants is venlafaxine.
Venlafaxine
(Effexor®)
Venlafaxine
is a novel SSRI chemically unrelated to other SSRIs but chemically
similar to the opioid tramadol (Ultram®) (Figure 1).(xxxvi)
Figure
1. The
chemical structures of venlafaxine and tramadol demonstrating the
chemical similarity between these two antidepressant and analgesic
substances, respectively.
The mechanism of the antidepressant
action of venlafaxine in humans is believed to be the same as with other
SSRIs, associated with its potentiation of neurotransmitter activity in
the CNS as with other SSRIs: preclinical studies have shown that
venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), are
potent inhibitors of neuronal serotonin and norepinephrine reuptake and
weak inhibitors of dopamine reuptake.
That
venlafaxine is analgesia is seen in studies in animals that show
that venlafaxine is effective in reversing chronic neuropathic pain
secondary to thermal hyperalgesia, and additionally is effective in
treating the hyperalgesia of neuropathic pain due to chronic sciatic
nerve constriction injury in rats.(xxxvii)
Venlafaxine-induced antinociception is
significantly inhibited by naloxone, nor-BNI and naltrindole but not by
beta-FNA or naloxonazine, implying involvement of kappa1- and delta-opioid
mechanisms. When adrenergic
and serotoninergic antagonists are used, yohimbine but not phentolamine
or metergoline, decreased antinociception elicited by venlafaxine,
implying a clear alpha2- and a minor alpha1-adrenergic mechanism of
antinociception. Therefore,
the antinociceptive effect of venlafaxine is mainly influenced by the
kappa- and delta-opioid receptor subtypes combined with the
alpha2-adrenergic receptor. These results suggest a potential use of
venlafaxine in the management of some pain syndromes.
However, further research is needed in order to establish both
the exact clinical indications and the effective doses of venlafaxine
when prescribed for neuropathic pain. (xxxviii)
SPINAL ALPHA-AGONISTS
Clonidine (Duraclon Injection®)
Recent studies using clonidine in central
and peripheral blockade show that it is co-analgesic when used with
either local anesthetics or opioids in epidural, intrathecal, or
peripheral blocks.(xxxix,xl) Clonidine is thought to have
applications in the treatment of chronic pain, particularly neuropathic
pain. Finally, intrathecal administration of clonidine has been
shown to reduce intractable muscle spasms in patients with spinal cord
injuries.
Alpha-2 receptors are located on primary
afferent terminals (both peripheral and spinal endings) in the
superficial laminae of the dorsal horn of the spinal cord, and within
several brainstem nuclei. The analgesic effect of clonidine may be
at all three sites, with each site’s relative contribution to its
analgesic effect being unclear. Most studies support a direct and
primary spinal analgesic action of clonidine. Supportive data for
this conclusion are the facts that the relative potency of epidural
clonidine to intravenous clonidine is 2:1, clonidine has a lipophilicity
similar to fentanyl, the duration of analgesia of epidural clonidine is
3-5 hours, and that intrathecal administration of clonidine results in a
peak effect within 30-60 minutes and has duration of up to 6 hours.
Clonidine increases the release of
acetylcholine at the dorsal horn. This enhances sensory and motor
block of C and A-delta fibers by local anesthetics by increasing
potassium conductance.
Adverse effects of clonidine include:
-
Dose
dependent decrease in blood pressure. Action at the nucleus
tractus solitarius and locus coeruleus decrease peripheral
sympathetic tone. Further action at the lateral reticular
nucleus causes hypotension and an antiarrythmogenic action.
Neuraxial administration inhibits sympathetic preganglionic neurons
in the spinal cord, and heart rate may decrease secondary to a
depression in atrioventricular nodal conduction.
-
Sedation.
This side effect is localized to the activity in the locus coeruleus.
The sedation is dose dependent between 50-900 µg regardless of
route of administration. Clonidine has a rapid onset of
sedation within 20 minutes. In adults, an infusion of epidural
clonidine of 30 µg per hour does not produce more sedation than
epidural placebo or epidural morphine.
-
Endocrine
depression. Clonidine reduces but does not suppress
neurohormonal secretion.
-
Sudden
cessation of clonidine treatment, regardless of the route of
administration and including after prolonged epidural
administration, has, in some cases, resulted in symptoms such as
nervousness, agitation, headache, and tremor, accompanied or
followed by a rapid rise in blood pressure.
Clonidine
alone does not induce respiratory depression nor potentiate respiratory
depression from opioids.
With
regards to the pediatric literature, most studies have been performed
using clonidine in combination with a bupivacaine epidural analgesia in
the acute pain setting. Motsch (xli) studied a group of 40
children undergoing minor surgical procedures. He found that
combined caudal analgesia with bupivacaine and clonidine (5 µg/kg) was
superior to local anesthetic alone, as determined by both duration and
intensity of analgesia. However, children had decreased blood
pressure and sedation for the first three postoperative hours.
This observed effect is consistent with the known duration of epidural
clonidine in adults. Other authors have studied caudal
analgesia using bupivacaine and clonidine, 1-2 µg/kg, with bupivacaine.
This dose of clonidine was seen to decrease mean arterial pressure but
not to cause bradycardia or respiratory depression. (xlii,xliii,xliv)
The
experience in adult cancer patients with intractable pain suggests an
initial dose of 30-150 µg followed by a continuous infusion of 8-400 µg/day.
Extrapolation from experience in adults and our unpublished clinical
experience suggests an initial dose of epidural clonidine of 1-2 µg/kg
should also be appropriate either in the subarachnoid or epidural
spaces, followed by an infusion of local anesthetic and clonidine at
0.02-0.1 µg/kg/hr, titrating as needed to a maximum of 0.2 µg/kg/hr,
while observing for undesired hemodynamic effects or sedation.
Table
2.
Summary of
unconventional analgesics useful in the management of pain in children.
|
Drug
|
Indications
and Uses
|
Pediatric
Dosing
|
Toxicity
and
Notes
|
|
Lidocaine
|
·
Neuropathic pain
·
Refractory visceral pain
|
150
µg/kg/hr
|
·
Measure plasma level every 8-12 hr and maintain 2-5 µg/ml
|
|
Mexiletine
|
·
See Lidocaine
|
See
Table 1
|
·
See Table 1
|
|
Carbamazepine
|
·
Neuropathic pain
·
Migraine prophylaxis
|
15-30
mg/kg
|
·
Blood dyscrasias
·
Monitor plasma level and periodic CBC
|
|
Valproate
|
·
Neuropathic pain
·
Migraine prophylaxis
·
Mood lability
|
10-60
mg/kg
|
·
Blood dyscrasias; hepatotoxicity
·
Dose divided BID.
Monitor plasma level and periodic CBC and LFT
|
|
Gabapentin
|
·
Neuropathic pain
·
Migraine prophylaxis
|
5-30
mg/kg
|
·
Dose divided TID or QID.
Escalate dose over several weeks to target dose
|
|
Amitriptyline
Nortriptyline
Imipramine
|
·
Neuropathic pain
·
Migraine prophylaxis
|
0.05-2
mg/kg
|
·
Escalate dose over several weeks to target dose.
Dose given h.s. Obtain
screening ECG prior to use: contraindicated in prolonged QTc
|
|
Venlafaxine
|
·
Chronic pain with depression
·
Neuropathic pain
|
1-2
mg/kg
|
·
Dose divided BID or TID
·
Caution when used with TCAs or other SSRIs because of
reported arrhythmias
|
|
Clonidine
|
·
Neuropathic pain
·
Visceral pain
·
Postoperative pain
|
0.05-0.2
µg/kg/hr
|
·
By continuous epidural infusion
·
May produce hypotension, bradycardia, somnolence
|
CAPSAICIN
Capsaicin is the chemical substance in chili peppers that creates their
spiciness and heat.
In 1997, a gene that encoded for a receptor specific for capsaicinoids
was identified. The capsaicin-gated vanilloid receptor 1 (VR1) is a
fatty acid receptor present only on C fibers, that when activated
produces desensitization or degeneration of the sensory afferent. This
phenomenon has led to the use of capsaicin for the management of chronic
pain states, particularly those associated with burning cutaneous
dysesthesias and mechanical allodynia. However, there are some
conditions for which capsaicin is ineffective, such as peripheral
neuropathy associated with the acquired immune deficiency syndrome
(AIDS) and neuropathic pain associated with nerve injury.
Overall, outcome studies show that the "number needed to
treat" (NNT) with capsaicin varies from 2.5 in painful diabetic
neuropathy, to 5.9 in other disorders. This is not an impressively
effective treatment modality, and the inconvenience of the necessity to
spread a cream over a large affected body surface.
Chronic application of capsaicin leads to
depletion of substance P from cutaneous C fibers, and ultimately
degeneration of C fibers, thus some degree of analgesia. However, acute
cutaneous application of capsaicin produces a complex sensation that
changes in intensity and quality as a function of time and is
characterized by sting, prick, burn and pain. The painful sensations and
inconvenience associated with acute application of capsaicin to affected
skin clearly limits its usefulness in pediatric pain medicine.
Furthermore, there are no published reports of the use of capsaicin in
children.
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