Biomedical Engineering Reference
In-Depth Information
channel currents, was recognized [
125
]. From early 1980s, it was demonstrated that
sodium channel blockade contributes to the efficacy of amitriptyline and other
tricyclic antidepressant used to treat pain [
126
-
128
], and the use of sodium channel
blockers became a great focus of attention for the treatment of neuropathic pain
[
129
-
131
]. Sodium channel blockers have currently been included not only in
therapies controlling surgical pain, but they are also employed for the management
of chronic pain conditions. In fact, there are several experimental evidences
concerning the capacity of LA, tricyclic antidepressant and other sodium channel
blockers to relieve neuropathic pain [
132
-
136
]. Anticonvulsant, antiarrythmics,
LAs and tricyclic antidepressants are currently used to treat this pathology, by the
virtue of their ability to modulate VGSCs. All the drugs currently used are sodium
channel antagonists with analgesic properties acting as state-dependent blockers.
Their actual efficacy is, to date, under investigation due to their low tolerability and
to the numerous adverse effects observed. In fact, all the available sodium channel
blockers used to treat chronic pain have shown severe tolerability limitations: the
off-target adverse effects of these drugs made very narrow their therapeutic margin
causing CNS liabilities as seizures, ataxia, confusion and sedation. For example,
phenytoin is associated with rash, gingival hypertrophy, horizontal nystagmus, and
teratogenicity, while carbamazepine can produce bone marrow suppression and
tocainide can provoque bone marrow suppression and pulmonary fibrosis so it is no
longer marketed in US. Mexiletine is poorly tolerated due to induced gastrointesti-
nal upset and the sedative and anticholinergic side effects of tricyclic antidepressant
can limit their therapeutic use. As a consequence to that, to maintain plasma
therapeutic levels of sodium channel blockers a medical follow-up and often
titration are necessary. Hereafter are presented the most interesting compounds
recognized as useful drugs in the treatment of several chronic pain conditions.
Lamotrigine (Fig.
3
): lamotrigine is clinically used for the treatment of epilepsy,
schizophrenia, bipolar disorder and Huntington's chorea, and it is under evaluation
for the treatment of neuropathic pain even if with often diverging results. For
instance, a 2006 clinical trial, involving patients with neuropathic pain induced
by chemotherapy did not show a significant difference between drug and placebo
efficacy but, in a previous study, conducted in 2001 on patients suffering from
diabetic neuropathy, lamotrigine showed a remarkable efficacy in pain control
[
137
]. Again, in a similar study involving patients with spinal cord injury-induced
neuropathic pain, lamotrigine was ineffective. In 2000 lamotrigine was used to treat
HIV-associated neuropathy and it was effective only on patients exposed to neuro-
toxic antiretroviral therapy [
138
]. Lamotrigine was also effective in the treatment of
post-stroke pain [
139
].
Topiramate (Fig.
3
): topiramate has been used for the treatment of epilepsy,
schizophrenia, bipolar disorder, and migraine. Recently, it has produced unclear
results in the treatment of neuropathic pain; in particular, the results obtained from
studies on diabetic neuropathy were not encouraging [
140
]. The most important
drawback for the use of topiramate in the treatment of neuropathic pain is its broad
and severe side effects such as dizziness, ataxia, speech disturbance, and visual
impairment [
140
].
