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| October 2014 -
Volume 12 Issue 8 |
|
Therapeutic
effect of pregabalin, Vitamin B-groups and their
combination on patients with diabetic peripheral
poly neuropathy
Kawa
F. Dizaye
Talar Ameer Sheet
Hawler Medical University, Erbil, Iraq
Correspondence:
Dr. Kawa Dizaye, Professor of Pharmacology,
Hawler Medical University, Erbil, Iraq
Tel: 009647504452392.
Email: doctorkawa@gmail.com
|
Abstract
Background and Objective:
The main micro vascular complications
of diabetes mellitus (DM) are neuropathy,
nephropathy and retinopathy. This study
was designed to evaluate and compare the
effectiveness of pregabalin, Vitamin B-groups
and their combination in treating patients
with diabetic peripheral neuropathy (DPN).
Methods and patients: Fifteen healthy
volunteers and 45 patients with diabetic
neuropathy with HbA1c ranging between
(6.7-12.2) % were included in this study.
The patients were randomized into three
groups of 15 patients each. The first
group received pregabalin capsule for
six weeks. The second group received B-complex
tablet (B1 vitamin, B6 vitamin, B12 vitamin)
twice daily for six weeks. The third group
received pregabalin capsule with B-complex
tablet for six weeks.
Results: Pregabalin did not significantly
improve the latency of nerve conduction
study in patients with DPN, but pregabalin
induced a significant improvement in the
amplitude of right peroneal nerve at the
ankle, left peroneal nerve at the ankle,
left peroneal nerve at the fibular head
and left tibial nerve at the popliteal
fossa, while pregabalin could induce a
significant improvement in the conduction
velocity of right tibial nerve and left
tibial nerve. Administration of Vitamin
B-groups demonstrated a significant improvement
in the latency of right tibial nerve at
the ankle and left tibial nerve at the
popliteal fossa of patients with DPN when
compared to the pretreated patients. Furthermore,
vitamin B-groups showed an improvement
in the latency of left peroneal nerve
at the ankle and left tibial nerve at
the ankle in patients with DPN, whereas
vitamin B-groups showed a significant
improvement in the amplitude of right
peroneal nerve at the fibular head. Daily
use of vitamin B-groups produced a significant
improvement in the conduction velocity
of right peroneal nerve. Administration
of the combined drugs did not significantly
improve the latency of left peroneal nerve
at the fibular head, right and left tibial
nerve at the ankle, right and left tibial
nerve at the popliteal fossa in patients
with DPN. Nonetheless combination of pregabalin
and vitamin B-groups induced a significant
improvement in the amplitude of right
peroneal nerve at the ankle, left peroneal
nerve at the ankle, right peroneal nerve
at the fibular head, right tibial nerve
at the popliteal fossa, and left tibial
nerve at the popliteal fossa of patients
with DPN. Nonetheless the combined drugs
could significantly recover the conduction
velocity of left tibial nerve in DPN patients.
Patients receiving pregabalin for six
weeks demonstrated a significant increase
in the level of direct bilirubin and aspartate
aminotransferase (AST). Receiving pregabalin
treatment has no hazardous effect on the
kidney function. Pregabalin had significantly
increased the serum level of malondialdehyde
of patients with diabetic peripheral neuropathy.
Conclusion: Vitamin B-groups were
more efficacious than the pregabalin in
improving latency of patients with DPN,
while combined drugs have significantly
caused greater improvement in the amplitude,
than the pregabalin and vitamin B-groups.
However no significant differences were
found between pregabalin, Vitamin B-groups,
and their combination in improving the
conduction velocity in patients with DPN.
Key words: diabetic peripheral
neuropathy, pregabalin, Vitamin B-groups
|
Neuropathy is considered the most common micro-vascular
complication of both types 1 and 2 diabetes mellitus
affecting up to 50% of type 2 diabetic patients
(1, 2). Increasing age, longer duration of diabetes
and poor glycaemic control are well recognized
risk factors for diabetic peripheral neuropathy
(DPN), while cigarette smoking, hypertension,
obesity, hyperlipidaemia and microalbuminuria
have also been implicated as potential risk markers
(3).
Diabetic peripheral neuropathy is considered a
main risk factor for amputation, and hence a significant
cause of morbidity in DM (4). Neuropathic disorders
in diabetes can impair the function of the central,
peripheral and/or autonomic nervous systems (5).
The typical DPN is a chronic, symmetrical, length
- dependent sensory motor polyneuropathy (6).
Distal symmetrical sensorimotor polyneuropathy
is the most common type of diabetic neuropathy.
It involves both small and large fibers and has
an insidious onset. Typically, the most distal
parts of the extremities are affected first, resulting
in a stocking pattern of sensory loss (7), which
is characterized by pain, numbness, and tingling
in the extremities and slow nerve conduction (8).
The diagnostic criteria of DPN include the presence
of any abnormality (Nerve conduction velocity,
amplitude, or latency) in two or more nerves on
an electrophysiological test (9).
Many patients with DPN will require pharmacological
treatment for painful symptoms: several agents
have efficacy confirmed in published randomized
controlled trials, although with the exception
of Duloxetine and Pregabalin, none of the others
is specifically licensed for the management of
painful DPN (10). Treatments that may be beneficial
for painful diabetic neuropathy include a number
of antidepressants (eg, amitriptyline, duloxetine,
venlafaxine) and anticonvulsants (eg, pregabalin,
sodium valproate) as well as some topical agents
such as capsaicin cream, lidocaine patch, and
isosorbide dinitrate topical spray (11, 12). Many
studies suggest the use of vitamin B-complex for
the management of diabetic neuropathy. (13, 14).
Pregabalin is recommended as a first-line treatment
for neuropathic pain by the Neuropathic Pain Special
Interest Group of the International Association
for the Study of Pain (15). It is also recommended
as a first-line treatment for DPN and central
neuropathic pain by the European Federation of
Neurological Societies (16) and as first-line
treatment for DPN by the American Academy of Neurology
(17). The course of DPN is variable. A population
based study states that 10% of patients with DPN
had their symptoms worsened over two years, 81%
remained unchanged and 9% had improved (18).
Pregabalin 150-600 mg/day has been shown to be
effective at relieving pain and reducing pain-related
sleep interference in numerous well controlled
trials of patients with DPN (19).
The aim of this study was to evaluate and compare
the effectiveness of Pregabalin, Vitamin B-groups
and their combination in treating patients with
diabetic peripheral poly neuropathy, moreover
the effect of pregabalin on liver function, renal
function and oxidative stress.
This study was conducted
at the Leila Qasm Diabetic
centre, Erbil and Hawler
Teaching Hospital/Neurophysiology
Unit, Erbil, from January
2013 to September 2013.
Fifteen healthy volunteers
and forty five patients
with diabetic peripheral
neuropathy were included
in this study. Electromyography
and biochemical tests
were carried out on both
the healthy volunteers
and patients groups.
The control:
The control group consisted
of fifteen healthy volunteers.
The age of this group
ranged between 20 and
55 years. All those subjects
were healthy, symptom
free and with no history
of systemic disease or
family history of diabetes
mellitus. Among this group
there were no histories
of alcohol abuse, drug
intake, or any other alternative
cause of neuropathy.
The patient:
Forty five patients with
diabetic neuropathy with
HbA1c ranging between
(6.7-12.2) %, (Mean ±
SD= 9.44±1.47)
with age ranging between
(30-55) years, were enrolled.
This study was conducted
at the Laeila Qasm Diabetic
Centre, Erbil, Iraq. The
ethical approval was obtained
from the Ethical Committee
of the College of Medicine
at Hawler Medical University
based on the principles
of the declaration of
Helsinki as revised in
2000; all patient gave
informed consent.
The Inclusion criteria
were predefined as follows:
1- Both males or
females of any race over
18 years of age.
2- Patients with
either type1 or type2
diabetes, who have been
on stable anti diabetic
medication regimen for
at least 30 days prior
to randomization.
3- Duration of
painful diabetic peripheral
neuropathy was required
to be more than three
months.
The criteria for exclusion
were as follows:
1- History of smoking,
alcohol consumption, and
thyroid gland disorder.
2- Patients with
any kidney disorder or
any conditions that could
confound assessment of
pain due to diabetic peripheral
neuropathy.
Study protocol:
The patients were randomized
into three groups of 15
patients each
- The first group
received pregabalin capsule
(75mg twice daily) for
six weeks.
- The second group
received B-complex tablet
[B1 vitamin (250mg), B6
vitamin (250mg), B12 vitamin
(1mg)] twice daily for
six weeks. The third group
received pregabalin capsule
(75mg twice daily) with
B-complex tablet [B1 vitamin
(250mg), B6 vitamin (250mg),
B12 vitamin (1mg)] twice
daily for six weeks. The
blood samples from the
first group was taken
before, and six weeks
after the intervention
and the investigations
included liver function
test, renal function test,
HbA1c, and malondialdehyde.
Thereafter the patients
were sent to Electrophysiological
unit at Hawler Teaching
Hospital for performing
the nerve conduction study
before and six weeks after
receiving the medication.
The data of Motor nerve
conduction studies were
analyzed using (Nicolet,
Madison, WI, USA) software
program.
Effects of pregabalin
on nerve conduction
study of motor nerve
of lower limb.
Administration of pregabalin
75mg twice daily did
not significantly improve
the latency of right
tibial nerve at the
ankle, left tibial nerve
at the ankle, right
tibial nerve at the
popliteal fossa and
left tibial nerve at
the popliteal fossa
of patients with diabetic
peripheral neuropathy
when compared to the
control group. However
no significant differences
were found between the
latency of the control
group and patients with
DPN in right peroneal
nerve at the ankle,
left peroneal nerve
at the ankle, right
peroneal nerve at the
fibular head and left
peroneal nerve at the
fibular head Table 1.
Table 1: Effects
of pregabalin (75mg)
on latency (ms) of motor
nerve conduction study
of the lower limb in
patients with diabetic
peripheral neuropathy.
• Mean values ±
S.E are presented.
• ms= millisecond.
• The same letters
mean that there is no
significant difference.
• The different
letters mean there is
a significant difference
at p < 0.05
Effects of pregabalin
on amplitude:
The effects of pregabalin
on the amplitude (mv)
of the motor nerve conduction
study of lower limb
in patients with DPN
are shown in table (2).
Pregabalin induced a
significant improvement
in the amplitude of
right peroneal nerve
at the ankle, left peroneal
nerve at the ankle,
left peroneal nerve
at the fibular head
and left tibial nerve
at the popliteal fossa
when compared to the
pretreated patients
but did not significantly
reach the mean of the
control healthy group.
Pregabalin did not significantly
improve the amplitude
of right peroneal nerve
at the fibular head,
right tibial nerve at
the ankle, left tibial
nerve at the ankle and
right tibial nerve at
the popliteal fossa
in patients with DPN
when compared to the
control group as shown
in Table 2.
Table 2: Effects
of pregabalin (75mg)
on amplitude (mV) of
motor nerve conduction
study of the lower limb
in patients with diabetic
peripheral neuropathy.
• Mean values ±
S.E are presented.
• mV=millivolt
• The same letters
mean that there is no
significant difference.
• The different
letters mean there is
a significant difference
at p < 0.05
Effects of pregabalin
on conduction velocity:
As shown in Table 3
pregabalin did not significantly
improve the conduction
velocity of right peroneal
nerve and left peroneal
nerve in patients with
DPN when compared with
the control group. However
pregabalin could induce
a significant improvement
in the conduction velocity
of right tibial nerve
and left tibial nerve
when compared to the
positive control subject
but did not significantly
reach the mean of control
healthy group.
Table 3: Effects
of pregabalin (75mg)
on conduction velocity
(mm/s) of motor nerve
conduction study of
the lower limb in patients
with diabetic peripheral
neuropathy
 •
Mean values ±
S.E are presented.
• mm/s=millimeter
per second
• The same letters
mean that there is no
significant difference.
• The different
letters mean there is
a significant difference
at p < 0.05
Effects of vitamin
B-groups on nerve conduction
study of motor nerve
of lower limb.
Effects of vitamin B-groups
on latency:
Table 4 shows that vitamin
B-groups did not significantly
improve the latency
of left peroneal nerve
at the fibular head
and right tibial nerve
at the popliteal fossa
in patients with DPN
when compared with the
control group. Vitamin
B-groups demonstrated
a significant improvement
in the latency of right
tibial nerve at the
ankle and left tibial
nerve at the popliteal
fossa of patients with
DPN when compared to
the pretreated patients,
but did not significantly
reach the mean of control
healthy group. Furthermore,
vitamin B-groups showed
an improvement in the
latency of left peroneal
nerve at the ankle and
left tibial nerve at
the ankle in patients
with DPN, however, no
significant difference
was found between post-treated
patients and each of
healthy subjects and
the pre-treated group.
Moreover no significant
differences were observed
between the latency
of control group and
patients with DPN in
right peroneal nerve
at the ankle, right
peroneal nerve at the
fibular head, Table
4.
Table 4: Effects
of vitamin B-groups
[vitamin B1 (250mg),
vitamin B6 (250mg),
vitamin B12 (1mg)] on
latency (ms) of motor
nerve conduction study
of the lower limb in
patients with diabetic
peripheral neuropathy
• Mean values
± S.E are presented.
• ms= millisecond.
• The same letters
mean that there is no
significant difference.
• The different
letters mean there is
a significant difference
at p < 0.05
Effects of vitamin B-groups
on amplitude:
The effect of vitamin
B-groups including vitamin
B1 (250mg), vitamin
B6 (250mg), vitamin
B12 (1mg) on amplitude
(mv) of motor nerve
conduction study of
the lower limb in patients
with diabetic peripheral
neuropathy is shown
in Table 5. Daily uses
of vitamin B-groups
did not significantly
improve the amplitude
of patients with DPN
in right peroneal nerve
at the ankle, left peroneal
nerve at the ankle,
left peroneal nerve
at the fibular head,
right tibial nerve at
the ankle, left tibial
nerve at the ankle,
right tibial nerve at
the popliteal fossa,
left tibial nerve at
the popliteal fossa
when compared with the
control group. Vitamin
B-groups showed a significant
improvement in the amplitude
of right peroneal nerve
at the fibular head
when compared to the
pretreated patients
but did not significantly
reach the mean of the
healthy group.
Table 5: Effects
of vitamin B-groups
[vitamin B1 (250mg),
vitamin B6 (250mg),
vitamin B12 (1mg)] on
amplitude mV of motor
nerve conduction study
of the lower limb in
patients with diabetic
peripheral neuropathy.
• Mean values ±
S.E are presented.
• mV= millivolt.
• The same letters
mean that there is no
significant difference.
• The different
letters mean there is
a significant difference
at p < 0.05
Effects of vitamin B-groups
on conduction velocity:
Table 6 demonstrates
that the vitamin B-groups
have no significant
effects in the improvement
of conduction velocity
in left peroneal nerve
and left tibial nerve
of patients with DPN
when compared with the
control group.
However Vitamin B-groups
produced a significant
improvement in the conduction
velocity of right peroneal
nerve when compared
with the positive control
subjects but did not
significantly reach
the mean of the healthy
group. As far as the
right tibial nerve is
concerned, it appears
that vitamin B-groups
improved the conduction
velocity in patients
with DPN but no significant
difference was established
between post-treated
patients and each of
healthy subjects and
pre-treated group.
Table 6: Effects
of vitamin B-groups
[vitamin B1 (250mg),
vitamin B6 (250mg),
vitamin B12 (1mg)] on
conduction velocity
(mm/s) of motor nerve
conduction study of
the lower limb in patients
with diabetic peripheral
neuropathy.
• Mean values ±
S.E are presented.
• mm/s=millmeter
per second
• The same letters
mean that there is no
significant difference.
• The different
letters mean there is
a significant difference
at p < 0.05
Effects of combination
of pregabalin and vitamin
B-groups on nerve conduction
study of motor nerve
of the lower limb.
Effects of pregabalin
and vitamin B-groups
on the latency:
Table 7 shows that there
was improvement in the
latency of left peroneal
nerve at the ankle however
it was not significant.
The combined drugs did
not significantly improve
the latency of left
peroneal nerve at the
fibular head, right
and left tibial nerve
at the ankle, and right
and left tibial nerve
at the popliteal fossa
in patients with DPN.
No significant differences
were found between the
healthy group and patients
with DPN concerning
right peroneal nerve
at the ankle and right
peroneal nerve at the
fibular head.
Table 7: Effects
of pregabalin (75mg)
and vitamin B-groups
[vitamin B1 (250mg),
vitamin B6 (250mg),
vitamin B12 (1mg)] on
latency (ms) of motor
nerve conduction study
of the lower limb in
patients with diabetic
peripheral neuropathy
• Mean values
± S.E are presented.
• ms= millisecond.
• The same letters
mean that there is no
significant difference.
• The different
letters mean there is
a significant difference
at p < 0.05
Effects of pregabalin
and vitamin B-groups
on the amplitude:
Table 8 shows that
combination of pregabalin
and vitamin B-groups
induced a significant
improvement in the amplitude
of right peroneal nerve
at the ankle, left peroneal
nerve at the ankle,
right peroneal nerve
at the fibular head,
right tibial nerve at
the popliteal fossa,
and left tibial nerve
at the popliteal fossa
of patients with DPN
when compared with the
positive control subjects
but did not significantly
reach the mean of the
control healthy group.
In left peroneal nerve
at the fibular head
the combination of pregabalin
and vitamin B-groups
significantly increased
the mean value of amplitude
of diabetic patients.
However, the combined
drugs have no significant
effects on the amplitude
of right tibial nerve
at the ankle and left
tibial nerve at the
ankle in patients with
DPN.
Table 8: Effects
of pregabalin (75mg)
and vitamin B-groups
[vitamin B1 (250mg),
vitamin B6 (250mg),
vitamin B12 (1mg)] on
amplitude mV of motor
nerve conduction study
of the lower limb in
patients with diabetic
peripheral neuropathy
• Mean values
± S.E are presented.
• mV= millivolt.
• The same letters
mean that there is no
significant difference.
• The different
letters mean there is
a significant difference
at p < 0.05
Effects of pregabalin
and vitamin B-groups
on conduction velocity:
The effects of the
combined drugs on the
conduction velocity
in DPN patients and
in comparison with the
healthy group are shown
in Table 9. Daily administration
of both pregabalin and
vitamin B-groups non-significantly
improved the conduction
velocity of right peroneal
nerve, left peroneal
nerve, and right tibial
nerve in DPN patients.
Nonetheless the combined
drugs could significantly
recover the conduction
velocity of left tibial
nerve in DPN patients.
Table 9: Effects
of pregabalin (75mg)
and vitamin B-groups
[vitamin B1 (250mg),
vitamin B6 (250mg),
vitamin B12 (1mg)] on
conduction velocity
(mm/s) of motor nerve
conduction study of
the lower limb in patients
with diabetic peripheral
neuropathy
• Mean values
± S.E are presented.
• mm/s=millimeter
per second
• The same letters
mean that there is no
significant difference.
• The different
letters mean there is
a significant difference
at p < 0.05
The net effects of pregabalin,
vitamin B-groups, and
their combination on
the motor nerve of the
lower limb after six
weeks treatment.
The net effects of pregabalin,
vitamin B-groups and
their combination on
the latency:-
The comparison of
the net differences
in the studied latency
before and after six
weeks treatment between
pregabalin, vitamin
B-groups, and their
combination is shown
in Table 10. Vitamin
B-groups have significantly
greater improvements
in the latency of right
and left tibial nerve
at the popliteal fossa
than that of pregabalin
and combined drugs.
No significant differences
were found between the
net effects of pregabalin,
vitamin B-groups, and
their combination in
the latency of right
peroneal nerve at the
ankle, or left tibial
nerve at the ankle.
Both vitamin B-groups
and combined drugs have
significantly better
effects than those of
pregabalin in the latency
of right peroneal nerve
at the fibular head.
However vitamin B-groups
and pregabalin have
higher affinity in reducing
latency than the combined
drugs of left peroneal
nerve at the ankle,
left peroneal nerve
at the fibular head,
and right tibial nerve
at the ankle.
Table 10: The net differences
in the studied latency
(ms) before and after
six weeks treatment
between pregabalin (75mg),
vitamin B-groups [vitamin
B1 (250mg), vitamin
B6 (250mg), vitamin
B12 (1mg)], and their
combination (n=45).
• Mean values
± S.E are presented.
• ms= millisecond.
• The same letters
mean that there is no
significant difference.
• The different
letters mean there is
a significant difference
at p < 0.05
The net Effects of pregabalin,
vitamin B-groups and
the combination of both
drugs on the amplitude:
The comparison of
the net differences
in the studied amplitude
before and after six
weeks treatment between
(pregabalin, vitamin
B-groups, and their
combination) is shown
in Table 11. The combined
drugs showed significantly
a greater improvement
in the amplitude of
right peroneal nerve
at the ankle, left peroneal
nerve at the ankle,
left peroneal nerve
at the fibular head
and right tibial nerve
at the popliteal fossa
in patients with DPN,
than that of pregabalin
and vitamin B-groups.
Combined drugs and pregabalin
have slightly greater
affects in the amplitude
of right peroneal nerve
at the fibular head,
right tibial nerve at
the ankle, and left
tibial nerve at the
ankle than that of vitamin
B- groups but the result
was not significant.
Both the combined drugs
and pregabalin produced
significantly greater
improvements of the
amplitude in left tibial
nerve at the popliteal
fossa than the vitamin
B-groups.
Table 11: The net
differences in the studied
amplitude (mV) before
and after six weeks
treatment between pregabalin
(75mg), vitamin B-groups
[vitamin B1 (250mg),
vitamin B6 (250mg),
vitamin B12 (1mg)],
and their combination
(n=45)
• Mean values ±
S.E are presented.
• mV= millivolt.
• The same letters
mean that there is no
significant difference.
• The different
letters mean there is
a significant difference
at p < 0.05
The net effects of
pregabalin, vitamin
B-groups and combination
of both drugs on conduction
velocity:
Table 12 shows that
no significant difference
were found among (pregabalin,
vitamin B-groups, and
their combination) on
the conduction velocity
of the right peroneal
nerve, left peroneal
nerve, and right tibial
nerve. While combined
drugs has shown a significantly
larger improvement in
the conduction velocity
of the left tibial nerve
than either of pregabalin
and vitamin B-groups.
Table 12: The net
differences in the studied
conduction velocity
(mm/s) before and after
six weeks treatment
between pregabalin (75mg),
vitamin B-groups [vitamin
B1 (250mg), vitamin
B6 (250mg), vitamin
B12 (1mg)], and their
combination (n=45)
• Mean values ±
S.E are presented.
• mm/s= millimeter
per second
• The same letters
mean that there is no
significant difference.
• The different
letters mean there is
a significant difference
at p < 0.05
Effects of pregabalin
on biochemical test
(liver function test,
renal function test,
and serum malondialdehyde).
Effects of pregabalin
on liver function test:
Administration of pregabalin
capsule (75mg) twice
daily significantly
increased the serum
level of direct billirubin
(P=0.02) and aspartate
aminotransferase (P=0.048).
However pregabalin did
not significantly change
the serum level of indirect
billirubin, serum alkaline
phosphates, and alanin
aminotransferase Table
13.
Following six weeks
of treatment with pregabalin
(75 mg twice daily)
there were no significant
changes found in the
renal function test
of DPN patients.
Use of pregabalin for
six weeks significantly
increased serum level
of malondialdehyde of
patients with DPN.
Table 13: Effects
of pregabalin on liver
function test, renal
function test and malondialdehyde
µm/l . n=15
* (P<0.05) when compared
to control group
The peripheral nerve
in diabetic patients
is characterized by
progressive nerve fiber
loss with pan-modal
fiber size pattern (20,
21). In particular,
the nerve fiber degeneration
is length-dependent
and conspicuous in distal
portion. It has recently
been shown that small
fibers are preferentially
affected in early stages
of diabetic patients
followed by the involvement
of large fibers related
to reduced nerve conduction
velocity (22, 23). The
progressive nerve fiber
loss may be attributed
to ongoing axonal degeneration
or severe demyelination
(24). The axonal loss
leads to lower amplitudes,
and demyelination causes
prolonged latency and
slow conduction velocity
(25).
Effects of drug on
nerve conduction study
of motor nerve of lower
limb:
The result of this study
showed that administration
of pregabalin 75mg twice
daily for six weeks
did not produce significant
effect on the latency
of nerve conduction
study in patients with
diabetic peripheral
neuropathy. These results
support the results
of Arezzo et al (2008)
who reported that pregabalin
300 mg twice daily had
no statistically significant
effect on nerve conduction
in patients with DPN
(26).
The effect of pregabalin
(75mg twice daily) on
amplitude of NCS after
six weeks were significant
improvement of amplitude
of right and left peroneal
nerve at the ankle,
left peroneal nerve
at the fibular head,
left tibial nerve at
the popliteal fossa.
This result is inconsistent
with the finding of
Tucker (2006) who showed
that 600mg of pregabalin
daily for 13 week had
no clinically significant
changes in the nerve
conduction parameters
including amplitude
and conduction velocity
(27). However in right
peroneal nerve at the
fibular head, left and
right tibial nerve at
the ankle and right
tibial nerve at the
popliteal fossa pregabalin
had no significant effects
on the amplitude of
NCS. Hence, this part
of our results is in
agreement with the finding
of Tucker (2006) (27).
The results of the present
study showed that use
of pregabalin for six
weeks caused a significant
improvement in the conduction
velocity of right and
left tibial nerve. This
finding is incomparable
with the study of Mathur
et al (2014) as they
observed that administration
of pregabalin 600mg/d
for 12 weeks did not
produce significant
effects on the amplitude
and conduction velocity
(28).
In this study, vitamin
B-groups vitamin B1
(250mg), vitamin B6
(250mg), vitamin B12
(1mg) showed a significant
improvement in latency
of right tibial nerve
at the ankle and left
tibial nerve at the
popliteal fossa after
six weeks of therapy.
The same dose of vitamin
B groups significantly
increased conduction
velocity of right peroneal
nerve. These improvements
in the latency and conduction
velocity most probably
is attributed to the
role of vitamin B-groups
in formation and synthesis
of myelin, which is
the protective coating
that insulates the nerve
(29), also vitamin B-groups
can activate chemical
signals that help nerves'
survival and regeneration
(30, 31, 32).
However vitamin B groups
could not significantly
change the amplitude
of NCS of right and
left peroneal nerve
at the ankle, left peroneal
nerve at the fibular
head, right and left
tibial nerve at the
ankle, and right and
left tibial nerve at
the popliteal fossa.
This indicated that
vitamin B groups showed
no affect in the development
of axon of nerve fibers
(25, 29).
The results of the present
study showed that the
combination of pregabalin
and vitamin B groups
has no significant effects
in improving latency
of right and left peroneal
nerve at the ankle and
at the fibular head,
right and left tibial
nerve at the ankle and
at the popliteal fossa
and conduction velocity
of right peroneal nerve,
left peroneal nerve,
and right tibial nerve.
However the combined
drugs could significantly
improve the amplitude
of right peroneal nerve
at the ankle, left peroneal
nerve at the ankle,
right peroneal nerve
at the fibular head,
right tibial nerve at
the popliteal fossa,
and left tibial nerve
at the popliteal fossa,
and left peroneal nerve
at the fibular head.
These interesting results
might be attributed
to medication non-adherence
as reported by NCPIE
(2000) which states
that non-adherence can
take a variety of forms,
including not having
a prescription filled,
taking an incorrect
dose, taking medication
at the wrong time, forgetting
to take doses, or stopping
therapy too soon (33).
The net effects of
pregabalin, vitamin
B-groups, and their
combination on the motor
nerve of lower limb
after six weeks treatment.
The effect of vitamin
B-groups on latency
of right and left tibial
nerve at the popliteal
fossa, right peroneal
nerve at the fibular
head, left peroneal
nerve at the ankle,
left peroneal nerve
at the fibular head,
and right tibial nerve
at the ankle is better
than the pregabalin
and their combination.
Vitamin B-groups' effectiveness
in improving latency
might be contributed
to the potential role
of vitamin B-groups
in improving neuropathy
and maintaining the
health of small nerves
in lower extremities
(34, 35, 36).
Combined drugs has significantly
caused greater improvement
in the amplitude of
right peroneal nerve
at the ankle, left peroneal
nerve at the ankle,
left peroneal nerve
at the fibular head,
and right tibial nerve
at the popliteal fossa
than that of pregabalin
and vitamin B-groups,
however in right peroneal
nerve at the fibular
head, right tibial nerve
at the ankle and left
tibial nerve at the
ankle combined drugs
have slightly greater
effect on amplitude
than vitamin B-groups
and pregabalin but the
result was deemed to
be non-significant.
Donger and Swami (2013)
concluded that vitamin
B-groups play an important
role in the regeneration
of the myelin sheath
(37), and the pregabalin
may restore the function
of nerve. It is well
known that vitamin B1
(thiamin) is contributed
to the synthesis of
neurotransmitter acetylcholine
and it facilitates the
conduction of nerve
impulses through the
peripheral nerves. Thiamin
is also instrumental
in producing myelin,
while vitamin B12 or
cobalamin is required
for the manufacture
of healthy myelin (29).
There were no significant
effects of pregabalin,
vitamin B-groups and
their combination found
in conduction velocity.
Effect of pregabalin
on biochemical test
(liver function test,
renal function test,
and serum malondialdehyde):
In the present study,
patients receiving pregabalin
(75 mg twice daily)
demonstrated a significant
increase in the level
of direct bilirubin
and aspartate aminotransferase.
However, pregabalin
intake did not significantly
change the serum level
of indirect bilirubin,
serum alkaline phosphates,
and alanin aminotansferase.
These results support
the findings of (Sendra
et al, 2011) who reported
that administration
of pregabalin 25 mg
twice daily for 14 days
significantly induced
an elevation in liver
enzymes (AST, ALT and
total bilirubin) of
a 54 -year old patient
(38).
Following six weeks
of receiving pregabalin
treatment (75 mg twice
daily), there was no
significant change noted
in the level of blood
urea and serum creatinine
when compared to pre-treatment
levels. Hence, it can
be concluded that pregabalin
has no hazardous effect
on the kidney functions
according to the above
findings.
The use of pregabalin
for six weeks had significantly
increased the serum
level of malondialdehyde
in this study. It was
found by Kay et al,
(2012) that pregabalin
induces hypoxia and
increases endothelial
cell proliferation in
mice, daily administration
produced a significant
increase in an immunohistochemical
stain causing hypoxia
in the liver of mice
(39). The oxidative
stress that occurs during
cellular hypoxia is
likely involved in this
disorder. Indeed, the
reactive species were
demonstrated to inhibit
active substances, modulate
the signaling of intracellular
pathways, and mediate
enzymes activation,
which are known to play
a critical role in the
geneses and/or the outcomes
of this disorder (40)
Vitamin B-groups were
more efficacious than
the pregabalin in improving
latency of patients with
DPN. While combined drugs
have significantly caused
greater improvement in
the amplitude than that
of pregabalin and vitamin
B-groups. However no significant
differences were found
between pregabalin, Vitamin
B-groups, and their combination
in improving the conduction
velocity in patients with
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