GABAPENTIN (NEURONTIN)
IN THE MANAGEMENT OF PAINFUL
PERIPHERAL POLYNEUROPATHY
Gary A. Mellick, D.O., DAAPM
Larry B. Mellick, M.D., FAAP, FACEP
Novel Targets in the Treatment of
October 6 & 7, 1997
PAIN
The Westin Washington D.C. City Center
Washington DC
Novel Targets in the Treatment of Pain
An open clinical trial using gabapentin (Neurontin) in
the management of painful peripheral polyneuropathy.
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ansient pain models. Gabapentin likely manifests its pain relieving qualities by similar mechanisms in these patients.
2
GABAPENTIN (NEURONTIN)
Gabapentin (Neurontin), Parke-Davis Morris
Plains, NJ): G a b a p e n t i n i s d e s c r i b e d a s 1 -
(aminomethyl) cyclohexane acetic acid with an empirical
f o r m u l a o f C 99H 1177N o 22.
Gabapentin is indicated as
adjunctive therapy in the treatment of partial seizures
with and without secondary generalization in adults with
e p i l e p s y . 11 T h e m e c h a n i s m b y w h i c h i t p r e v e n t s s e i z u r e s
is unknown. Gabapentin is structurally related to the
neurotransmitter GABA (gamma-aminobutyric acid) but it
does not interact with GABA receptors.
Radioligand
binding assays showed that gabapentin does not exhibit
affinity for other common receptor sites.
Recent
research has shown that gabapentin binds to the alpha 2
d e l t a s u b u n i t o f v o l t a g e - d e p e n d e n t c a l c i u m c h a n n e l s . 22
3
AIM OF INVESTIGATION
Current therapy for many patients with painful
peripheral polyneuropathy remains frustratingly
difficult. We report the first author’s encouraging
experiences using gabapentin (Neurontin), a
novel anticonvulsant drug with a mechanism of
action apparently distinct from that of other
antiepileptic agents.
This initial list of ten patients ranging from
forty-eight to seventy-eight years of age,
represents the first reported series of patients
with painful peripheral neuropathy treated with
gabapentin.
4
METHODS
Peripheral neuropathy was confirmed in each
patient by a detailed neurologic examination,
nerve conduction study and electromyography
(EMG). Quantitative thermal sensory testing was
completed on selected patients.
Gabapentin was chosen because recent
reports described its effectiveness in the
management of reflex sympathetic dystrophy
pain33,,44,,55,,66 and because it is well tolerated and has a
benign efficacy-to-toxicity ratio. Treatment with
gabapentin was begun with 300 mg per day and
titrated upward to maximal pain relief.
5
RESULTS
The gabapentin dosage ranged from 300 to
2000-mg with an average dose of 900 mg per
day. All ten patients experienced significant
and sustained pain relief with only transient
central nervous system adverse effects.
Fortuitously, two patients reported relief from
refractory restless legs syndrome that had been
unresponsive to previous multiple therapies. All
patients reported improved quality of sleep.
Several patients described Anxiolytic and mood
enhancing effects.
6
DISCUSSION
Other authors have described gabapentin’s value for
the treatment of neuropathic pain. In 1996, Segal and
Rordof described gabapentin as a novel treatment for
postherpetic neuralgia77 while Schacter and Suter
identified gabapentin as a useful medication for the
treatment of central pain.99 Chevelle and colleagues
described the use of gabapentin for radiation
myelopathy88 pain. Rosner and colleagues discussed the
management of a variety of neuropathic pain states.1100
In this report, the authors document the use of
gabapentin in a series of patients with painful peripheral
polyneuropathy.
7
CONCLUSION
Recent research has identified that gabapentin
may relieve pain by binding to the alpha 2 delta
subunit of voltage-dependent calcium channels and
dose-dependently by which it inhibits the late phase
of the nociceptive response in inflammatory pain
models. Studies showed that gabapentin effectively
inhibited thermal and mechanical hyperalgesia but
failed to display an antinociceptive action in
transient pain models.11
Research to identify gabapentin’s novel pain
relieving mechanism in these patients is ongoing.
8
REFERENCES
1. Field MH, Oles RJ, Lewis AS, McCleary S, Hughes J, Singh L:
Gabapentin (Neurontin) and S-(+)-3-isobutylgaba represent a
novel class of selective antihyperalgesic agents. Br J
Pharmacolog 1997 Aug;121(8):1513-1522.
2. Gabapentin package insert, Parke-Davis company, Morris
Town, NJ
3. Mellick LB and Mellick GA: Successful treatment of reflex
sympathetic dystrophy with gabapentin. Am J. Emerg. Med.
1995;13:96.
4. Mellick GA and Seng ML: The use of gabapentin in the
treatment of reflex sympathetic dystrophy and a phobic
disorder. Am J. Pain Management 1995;5:7-9.
5. Mellick GA and Mellick LB: Gabapentin in the management
of reflex sympathetic dystrophy. J. Pain and Symptom
Management 1995; 10:265-266
9
REFERENCES
6. Mellick GA and Mellick LB: Reflex sympathetic dystrophy
treated with gabapentin. Arch. Phys Med Rehabil.1977;78:98105
7.
Segal AZ and Rordorf G: Gabapentin as a novel treatment for
postherpetic neuralgia. Neurology 1996;1175-1176
8. Cheville A et al: Neuropathic pain in radiation myelopathy: a case
report. Program book, American Pain Society (14th Annual
Scientific Meeting). Abstract #95823, Page A-115.
9. Schacter S. and Suter M: Treatment of central pain with
gabapentin: Case Reports. J. Epilepsy 1996;223-226.
10. Rosner H, et al: Gabapentin adjunctive therapy in neuropathic
pain states. Clin J. Pain . 1996;12:56-58.
10
PATIENTS TAKING GABAPENTIN
TABLE 1
Pt.
Underlying
Condition
1.
Diabetes Mellitus
48
Male
1600 mg/day
7 Months
75%
Drowsiness
Improved Sleep Quality
2.
Rheumatoid
Arthritis
Diabetes Mellitus,
Hypothyroidism
Paraneoplastic
Syndrome
Diabetes Mellitus,
Restless Legs
Syndrome
Unknown,
Familial
Diabetes Mellitus,
Hypothyroidism
Alcohol Abuse,
Prostate Cancer
Porphyria
77
Female
300-600 mg q hs
11 Months
45%
Improved Sleep Quality
59
Female
1200 mg/day
5 Months
75%
Unsteady
gait
None
78
Female
600-900 mg/day
11 Months
60%
Improved Sleep Quality
59
Female
900 mg/day
10 Months
80%
Unsteady
gait
None
62
Female
900 mg/day
5 Months
85%
None
59
Female
900 mg/day
9 Months
75%
Dizziness
Improved Sleep Quality
69
Male
2000 mg/day
6 Months
60%
None
Improved Sleep Quality
46
Male
1600 mg/day
2 Months
95%
Unknown,
Restless Legs
Syndrome
69
Female
300 mg q hs
6 Months
85%
Mild
Euphoria
None
Improved Sleep Quality,
Control of Leg Cramps
Improved Sleep Quality,
Control of Restless Legs
Syndrome Symptoms
3.
4.
5.
6.
7.
8.
9.
10.
Age Gender
Neurontin
Dose
Treatment % Pain
Relief
Adverse
Effects
Positive Effects
Improved Sleep Quality
Reduction of Leg Cramps
and Restless Legs
Syndrome, Improved Sleep
Improved Sleep Quality
11
GABAPENTIN (NEURONTIN)
IN THE MANAGEMENT OF PAINFUL
PERIPHERAL POLYNEUROPATHY
GARY A. MELLICK, D.O., DAAPM
PRESIDENT, AMERICAN PAIN SPECIALISTS
1100 N. ABBE RD, SUITES C & D  ELYRIA, OH 44035
LARRY B. MELLICK, M.D., FAAP, FACEP
CHAIR AND PROFESSOR, DEPARTMENT OF EMERGENCY MEDICINE
MEDICAL COLLEGE OF GEOR GIA  AUGUSTA, GA 30907
12