Transcript First Neurontin Pain Lecture

Gary A. Mellick, D.O.
American Pain Specialists, Inc.
My RSD
Sally Stauder
Reflex sympathetic dystrophy has been my constant companion for the past two and
one half years of my life. I fell on my basement steps on November 21, 1991 and since
then my life was changed. Up until then I thought that being a college educator would
be the most demanding challenge of my life. Little did I realize after six months and six
physicians later, when I finally learned my diagnosis, that I was about to travel down a
long, rocky road of pain and suffering, sleepless nights, crying and many hours of
vigorous physical and occupational therapy to my arm, wrist, and hand.
Following my diagnosis, my therapy consisted of stellate ganglion blocks, TENS unit
therapy, repeated peripheral anesthetic nerve blocks, and a list of prescribed
medications that barely took my pain away. A bone scan confirmed my dismay when
the burning pain spread to my left arm.
After being treated by Dr. Mellick for over one year, something miraculous happened to
me on Friday, May 20, 1994, when I took my first gabapentin capsule at 5 PM. Within two
hours after taking my first 300 mg capsule, I felt complete pain relief. This was followed
by six hours of beautiful uninterrupted sleep and when I awoke, I was exhilarated over
the magnitude of my pain relief! Of course, as with most medications, I experienced side
effects. Initially these included euphoria, mild disorientation, dizziness, and drowsiness.
They gradually resolved after several days. Later I experienced leg cramps, itching, and
episodic diarrhea which disappeared.
Nevertheless, the most amazing thing of all was that my pain racked body was now
becoming less sensitive to light touch and by day ten of gabapentin therapy, I was able
to hold my grand nephew in my arms for the first time (of course I cried).
Finger
movements had increased dramatically by day fifteen of therapy and occupational
therapy was now much less painful and my myofascial treatments were more effective.
Follow-up examinations with Dr. Gary Mellick showed that I had much less tenderness to
touch and by one month after starting gabapentin, I was able to firmly shake hands with
his office staff and experience no pain. My skin texture is normalizing, and my strength is
gradually improving. Best of all, my family reports that I am now back to my former self.
The awful depression has lifted and I am once again becoming an active participant in
life. I am free at last. I am no longer a prisoner in my own body!
Although I realize that not every one of you who read this will experience the same relief
that this medication has afforded me, I still hope and pray that your response is as
complete as mine. Thank God! At last there is hope for those of us who suffer with reflex
sympathetic dystrophy.
Gabapentin (Neurontin)
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An anticonvulsant introduced in February 1994.
Indicated for treatment of partial seizures with or
without secondary generalization.
GABA-mimetic, crosses blood brain barrier
Binds in outer cortex, hippocampus, etc.
Receptor and biochemical function unknown
Not protein bound, renal excretion
Not metabolized by liver
Benign efficacy-to-toxicity level
Neurontin: Pain Management
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Initial Clinical Experience
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Reflex Sympathetic Dystrophy - May 20, 1994
Phobic Disorder
Subsequent Clinical Experience
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Acute & Chronic Pain Syndromes
Cancer Pain
Difficulty Initiating & Maintaining Sleep (DIMS)
» With Pain
» Without Pain
Neurontin: Pain Management
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Neuropathic Pain Syndromes
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Visceral Pain Syndromes
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Musculoskeletal Pain Syndromes
MANAGEMENT
NEUROPATHY
PAINFUL PERIPHERAL
GABAPENTIN (NEURONTIN )
OF
WITH
GABAPENTIN RELIEVES ABNORMAL PAINS IN A RAT
MODEL OF PAINFUL PERIPHERAL NEUROPATHY:
W.H. Xiao and G.L. Bennett*, Neurobiology and Anesthesiology Branch,
NIDR, NIH, Bethesda, MD 20892
Gabapentin (1-(aminomethyl) cyclohexaneacetic acid; Neurontin)
is a cyclic GABA analog with an unique profile of anticonvulsant activity in
animal models, an unique binding pattern in brain, and an unknown
mechanism of action. An open label clinical trial (Mellick & Mellick, J. Pain
Symptom Mgmt, 10:1-2, ‘95) of gabapentin in patients
with reflex
sympathetic dystrophy suggests that it may have efficacy in the treatment
of
painful
peripheral
neuropathies.
Using
rats
with
the
chronic
constriction injury (CCI) of Bennett & Xie (Pain, 33:87-107, ‘88) and an
observer blinded as to drug condition, we have examined gabapentin’s
effects on hyperalgesia and allodynia following (2, 4 and 24 hr) i.p. and
lumbar intrathecal (i.t.) bolus injections on postoperative days 6-16 (at or
near the period of peak symptom severity). Prior to drug administration,
rats were shown to have statistically significant heat-hyperalgesia (paw
withdrawal method), mechano-hyperalgesia (pin-prick test and mechanoallodynia (von Frey hair test).
None of the i.p. and i.t. doses that we
examined produced any obvious motor side-effects and none had any
effect on the responses evoked from the sham-operated control side. In a
dose-response trial of i.p. gabapentin (saline, 10, 25 and 75 mg/kg), heathyperalgesia and mechano-allodynia were significantly reduced in a doserelated manner for up to 4 hr. In an i.t. dose-response trial (saline, 7.5, 15,
37.5, and 75 mg; all 10 ml volume), heat-hyperalgesia was significantly
reduced in a dose-related manner for up to 4 hr. An i.t. trial using 150 mg
of gabapentin failed to reveal any efficacy against mechano-hyperalgesia;
in the same animals this dose produced a significant suppression of heathyperalgesia
and
mechano-allodynia.
Our
results
suggest
that
gabapentin may be useful in the clinical management of painful peripheral
neuropathy and that its efficacy against heat-hyperalgesia and mechanoallodynia may be mediated largely or entirely by a spinal site of action.
SOC. NEUROSCI. ABSTR., 21 (1995) IN PRESS
Neurontin: Pain Management
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Neuropathic Pain Syndromes
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Peripheral Neuropathies/Neuralgias
Phantom Limb & Stump Pain
Herpes Zoster & Postherpetic Neuralgia
Central Pain (MS, Stroke, Etc.)
Complex Regional Pain Syndromes
»
Reflex Sympathetic Dystrophy (CRPS Type I)
»
Causalgia (CRPS Type II)
Sympathetically Maintained Pain
»
Neurontin: Pain Management
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Visceral Pain Syndromes
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Lungs & Pleura
Heart & Pericardium
Abdomen
»
»
»
»
»
Pancreas, Liver, & Biliary System
Chronic Pain After Surgery
Stomach & Gastrointestinal Tract
Kidney & Ureters
Pelvis & Perineum
Neurontin: Pain Management
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Musculoskeletal Pain Syndromes
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Whiplash Injury
Chronic Low Back Pain
Fibromyalgia
Restless Legs Syndrome & Periodic Limb
Movement Disorder
Neurontin: Pain Management
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Restless Legs Syndrome
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First described by Ekbom in 1945
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Characterized by: Irresistible leg movements,
dysesthesia, worse in the evening and at bedtime.
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Estimated prevalence of 5 to 10% of the population.
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Familial incidence in 1/3 of cases (Boghen &
Peyronnard, 1976)
Restless Legs Syndrome
PATIENTS TREATED WITH GABAPENTIN (NEURONTIN)
Table 1
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
PT
NAME
A.W.
B.E.
F.L.
G.E.
M.L.
N.B.
P.S.
S.J.
S.C.
S.J.
W.L.
B.J.
D.M.
D.G.
W.L.
H.D.
AGE
(YRS)
62
47
43
73
54
60
51
75
51
72
68
36
50
75
47
46
DURATION
OF RLS
10 YRS
9 YRS
15 YRS
30 YRS
6 YRS
20 YRS
10 YRS
10 YRS
3 YRS
11 YRS
20 YRS
30 YRS
25 YRS
40 YRS
15 YRS
>1 YRS
NEURONTIN
DOSE
400 PO TID
300 MG TID
400 5/D
300 MG BID
300 MG QHS
600 MG QHS
400 MG BID
400 MG BID
800 MG BID
800 MG QHS
300 MG TID
800 MG QHS
400 MG TID
400 MG 5/D
800 MG QHS
800 MG QHS
RLS
RELIEF
90%
75%
75%
100%
90%
50%
50%
90%
75%
100%
75%
95%
90%
80%
100%
100%