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J Res Adv Dent 2014; 3:1:19-22.

Pregabalin and its Efficacy in Trigeminal Neuralgia A Review

OmPrakash D Toshniwal1 Bhavna Barthunia2* Dinesh Bulchandani3 Kapil Dev Gupta4 Kapil

and Head, Department of Oral Medicine and Radiology, Daswani Dental College, Kota, Rajasthan, India.
2Reader, Department of Oral Medicine and Radiology, Daswani Dental College, Kota, Rajasthan, India.
3Senior Lecturer, Department of Periodontics, Daswani Dental College, Kota, Rajasthan, India.
4Senior Lecturer, Department of Periodontics, Daswani Dental College, Kota, Rajasthan, India.
5Senior Lecturer, Department of Oral Pathology, Daswani Dental College, Kota, Rajasthan, India.

Background: Trigeminal neuralgia is a relatively common neuropathic pain which is characterized by
paroxysmal, sharp, shooting, shocking or piercing pain in relation to branches of fifth cranial nerve. The pain is
usually uni-lateral lasting only for few seconds but sometimes may extend to few minutes. Various treatments
extending from medical to neurosurgical procedures are available. Carbamazepin being the first prefered drug
for the treatment of trigeminal neuralgia. The latest drug to hit the market is an antiepileptic drug pregabalin
(Lyrica) . This article reviews the efficacy and use of pregabalin in treatment of trigeminal neuralgia
Keywords: Trigeminal neuralgia, Pregabalin,neuropathic pain.
Trigeminal neuralgia (TGN) is a debilitating
neuropathic pain of maxillofacial region. The
disease is characterized by sharp, shooting, boring,
lancinating and piercing pain in relation to branches
of fifth cranial nerve.1,2 The pain attacks may result
from physiologic changes induced by chronic partial
injury to the brain stem trigeminal nerve root from
a variety of causes.3 The pain is characteristically
paroxysmal and is usually unilateral. The affected
nerves are responsible for sensing touch,
temperature sensation and pressure sensation in
the facial area from the jaw to the forehead 4
So pain is usually provoked by a mechanical
tactile stimulus like eating, talking, washing the face,
cleaning the teeth or touching to any area of face or
mouth. Sometimes, the pain may occur
spontaneously. However, there is no associated
neurosensory or motor nerve deficit.1

Each paroxysm of pain lasts only for few

seconds but sometimes may extend to few minutes.
Initially the gap between the two episodes is more.
With the advancement of disease the number of
bouts of pain increases in term of per month, per
week or per day.1
Some patients will have a muscle spasm
which led to the original term for TGN of "tic
douloureux" ("tic", meaning 'spasm', and
"douloureux", meaning 'painful',in French)5
The treatment of trigeminal neuralgia
continues to be major therapeutic challenge.
Medication is often the first line of treatment 6
The drug of choice of TGN is carbamazepine
and approximately 70% of the patients suffering
from this disease can be best treated for the painful
paroxysms with this drug; further 10-15 % can be
controlled by the addition or substitution of
phenytoin sodium(Eptoin) .Other drugs, which form


Copyright 2013

the second line of treatment are beclofen, Valproate

sodium, Gabapentine, pregabalin , topiramate or
clonazepam in single or combinations. 1
Pregabalin is an anticonvulsant drug used
for treatment of neuropathic pain and as an adjunct
therapy for partial seizures with or without
secondary generalization in adults. It is a GABA
analogue structurally related to gabapentin which
modifies the synaptic or non-synaptic release of
GABA. The drug binds to the a2d subunit of the
voltage gated calcium channels in the brain and
spinal cord causing decreased presynaptic calcium
entry leading to decreased synaptic release of
glutamate 7,8,9
Pregabalin is available in 25, 50, 75, 100,
150, 200, 225, and 300 mg capsules, and recently
a strawberry flavoured oral solution has been
developed, containing 20 mg/mL with an added
sweetening agent (sucrose) to mask the chemical's
bitter taste.10,11
The recommended dose be titrated,
according to response and tolerability, from 150
mg/day to 300 mg/day after 3-7 days and then to
600 mg a day after an additional 7 days. Patients
with compromised renal function should have their
dose of pregabalin reduced 12
The medication is widely used to treat all
kinds of neuropathic pain. Pregabalin does not
interact with other medications, which makes it
very easy to use. Its most common side effects are
fatigue and swelling in the legs. Weight gain over
time is commonly seen The other most common
adverse reactions are dizziness and somnolence12,13
Pregabalin has been tried in recalcitrant cases of
trigeminal neuralgia.14
Absorption: Pregabalin is rapidly absorbed when
administered on an empty stomach, with peak
plasma concentrations occurring within one hour.
Pregabalin oral bioavailability is estimated to be
greater than or equal to 90% and is independent of
dose. The rate of pregabalin absorption is decreased
when given with food resulting in a decrease in
Cmax by approximately 25 to 30% and a delay in
Tmax to approximately 2.5 hours. Administration

with food, however, has no clinically significant

effect on the extent of absorption.15
Distribution: Pregabalin has been shown to cross
the blood-brain barrier in mice, rats, and monkeys.
Pregabalin has been shown to cross the placenta in
rats and is present in the milk of lactating rats. In
humans, the volume of distribution of pregabalin for
an orally administered dose is approximately 0.56
L/kg and is not bound to plasma proteins.15
Metabolism: Pregabalin undergoes negligible
metabolism in humans.16 Approximately 98% of the
radioactivity recovered in the urine was unchanged
pregabalin. The major metabolite is N-methyl
Excretion: Pregabalin is eliminated from the
systemic circulation primarily by renal excretion as
unchanged drug.15 Renal clearance of pregabalin is
73 mL/minute.
To compare its efficiency with gabapentin,
another drug used in the treatment of trigeminal
neuralgia Fink K performed a homologous
competitive binding experiment to determine
receptor number and affinity of pregabalin for
human CNS tissue (Table I). They used post-mortem
human neocortical tissue from male individuals
with no neurological disease who deceased from
heart attack to find the binding ability and compare
it with Gabapentin. They found that
concentration of pregabalin as compared to
gabapentin was able to reduce the binding of radiolabeled gabapentin to human neocortical tissues by
50%. This indicates that pregabalin binds to human
CNS tissues (2 sub-unit of VGCC) with greater
affinity than gabapentin.
Extremely high concentrations of r-isobutyl GABA
were required to reduce the binding of radiolabeled gabapentin by 50%, indicating poor binding
affinity of the former.17
The efficacy of pregabalin treatment has
also been tried in patients suffering from trigeminal
neuralgia with and without concomitant facial pain
where patients received pregabalin (PGB) 150-600
mg daily and were prospectively followed for 1
year. The primary outcome was number of patients
pain free or with reduction of pain intensity by >
50% and of attack frequency by > 50% after 8


weeks. Secondary outcome was sustained pain

relief after 1 year. 18
The efficacy and safety of the drug
pregabalin (PGB) and its reduction in pain intensity
was evaluated where pregabalin (150-600 mg/day)
along with oxycodone CR( 20 mg/day) reduced the
acute facial pain and other symptoms caused by
trigeminal neuralgia 2

with trigeminal neuralgia deserve an accurate and

dispassionate explanation of the merits and
drawbacks of all methods of treatment from the
outset. The drug Pregabalin requires more research
and studies in this matter.
Collaborative research is destined to yield
new targets for drug treatment and, more broadly,
new knowledge of pain mechanisms.

Prez C,et. al analyzed

the effect of
pregabalin (PGB) on pain alleviation, use of health
care and non-health care resources, and associated
costs in patients with trigeminal neuralgia under
usual clinical practice in primary care settings.
Sixty-five pregabalin nave patients received
pregabalin as monotherapy (n = 36, 55%) or
combined with other drugs (n = 29, 45over a 12week, multicenter, observational prospective study .
It was concluded that pregabalin as monotherapy or
combined with other drugs is effective in pain
management in patients with trigeminal neuralgia
and reduces the cost of illness.19
Prez C et. al. assessed the effects of
pregabalin (PGB) on patient-reported health
outcomes in 65 PGB-naive subjects with trigeminal
neuralgia refractory to previous analgesic therapy
in a prospective, multicenter observational study
carried out in primary care. Twelve weeks'
monotherapy with PGB reduced baseline intensity
of pain. Anxiety/depression symptoms also
decreased .PGB improved sleep and patient
functioning. The results supported the effectiveness
of PGB for the improvement in pain and related
health symptoms.20
The Rustagi et al. study was a randomised,
cross-over trial comparing the efficacy of pregabalin
with lamotrigine and was published as a conference
abstract . The authors concluded that although the
efficacy of pregabalin was comparable to
lamotrigine, pregabalin was found to have better
tolerability, which would increase patient
compliance when compared with lamotrigine.21

Table 1: Comparison of affinity of pregabalin

gabapentin, in a homologous competitive binding experiment
to determine receptor number and affinity to human CNS
No potential conflict of interest relevant to this
article was reported.

Syed S. Ahmed, Afshan Bey, Sarwat H. Hashmi.

Trigeminal neuralgia - A neuropathic pain.
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Giordano G, DArienzo S, Stumbo R, Coletta F,

Bernardo A, Coviello A, Colella U., Gritti F, Diglio
V, Aurilio C Trigeminal neuralgia:Efficacy and
safety of pregabalin with oxycodone controlled
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Scrivani SJ, Mathews ES, Maciewicz RJ

Trigeminal neuralgia. Oral Med Oral Pathol
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It is essential that clinicians recognize and
diagnose trigeminal neuralgia correctly for patients
to receive appropriate referral and therapy for this
relatively treatable condition. Meanwhile, patients



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