Diabetic neuropathy (DN) is a persistent complication of diabetes mellitus (DM).
It affects approximately thirty to fifty percent of subjects who have this ailment. DM
has become the most common causative factor of polyneuropathy in today’s world.
So much so that fifty percent of the neuropathies are linked to DM. It badly affects the
quality of life (QOL) of those suffering from it. On top of it, Polyneuropathies cause
chronic neuropathic pain, bringing depression, anxiety, and insomnia among its sufferers.
Diabetic neuropathy is a painful and disabling condition that has huge costs in
terms of deranged quality of life and financial repercussions linked to their treatment.
Various painkillers have been tried in this regard with varying results. The aim of this
review was to delve into various drug outcomes in this regard.
Diabetic neuropathy (DN) is a common complication of diabetes
mellitus (DM). Its prevalence reaches up to fifty percent in subjects
suffering from this ailment [1]. It is more prevalent in chronic
DM and it has a negative impact on the quality of life (QOL) of those
suffering from it. Polyneuropathies cause chronic neuropathic pain,
which leads to heavy personality costs in terms of depression, anxiety,
and insomnia among sufferers [1-3]. Diabetic neuropathies can
be classified into generalized and focal/multifocal forms. The most
common subtype of diabetic neuropathy is dependent on the length
and manifests as a symmetrical sensory-motor peripheral polyneu
ropathy [4]. Its pathogenesis can be explained in a nutshell as a sys
tem of metabolic derangements, such as hyperglycemia, accelerated
polyol flux, enhanced oxidative stress, and lipid alterations [4-8].
In recent criteria (Toronto consensus criteria) a framework for Diabetic
Neuropathy diagnosis was formulated. Toronto consensus criteria
took into account the combination of neuropathy symptoms
and signs that could be confirmed using nerve conduction studies
[7]. Nerve conduction studies are normal in small fiber neuropathy,
so the most used diagnostic tool for small fiber neuropathy is a skin
biopsy with the assessment of intraepidermal nerve fiber density
[8,9]. A few of the recent developments regarding Diabetic Neuropathy include new biomarkers for early and accessible diagnosis, assessing metabolic risk factors, innovations in clinical trials relevant
to painful diabetic neuropathy, genetic modifiers risk factors, and
new therapeutic advancements.
We did a search on PubMed, and Medline database publications
using: diabetic neuropathy, developments, painkillers, chronic
pain, complications, and Pain control. The publications included
were special communications, reviews, conference papers, books,
and research studies regarding the subject matter over last twenty
years.
Diabetic polyneuropathy is can be defined as the occurrence of
symmetrical, distal, and progressive degeneration of the sensorimotor
and autonomic peripheral fibers, ascribable to metabolic and
microvascular alterations due to chronic hyperglycemia [10-12].
More than four hundred million people suffer from diabetes mellitus
globally [11-14]. Out of these, one-fourth fall prey to chronic
painful diabetic neuropathy (PDN). Such kind of pain starts distally,
and is remarkably unpleasant at night, and follows a proximal
and symmetrical progression: discomfort starts in the toes, feet,
then follows the ankles. It is a “burning” sensation accompanied
by a feeling of tingling. Uncommonly, it may manifest as allodynia
(sensitive to touch such as combing hair), wherein normal activities
lead to pain [15,16]. It is a major challenge in the screening process
for DPN that once a neuropathy becomes detectable by recently applied
assessments; nerve injury is well-progressed and very difficult
to reverse [17,18]. Hence, it is the need of the hour to formulate
more sensitive biomarkers as screening and diagnostic tools and
surrogate end-point measures [17]. There is a need for accurate
diagnosis of various DPN types, especially small fiber neuropathy,
which is vital for clinical trial design and to help find specified therapeutic
interventions. There is a need for the development of minimally
invasive and simplified biomarkers to facilitate diagnosis and
design of clinical trials for disease prevention or timely intervention
to slow their progression.
For example, Corneal confocal microscopy is a new noninvasive
technique that can help in the detection and quantification of small
nerve fiber loss in DPN and other forms of neuropathy [18,19].
A confocal laser scanning microscope noninvasively visualizes
small-diameter unmyelinated axons in the cornea. Patients with
DPN have reduced corneal nerve fiber density and length compared
with normal controls [19]. More validation studies are required
before corneal confocal microscopy can be used as an alternative
measure of small-caliber nerve fiber loss. Nerve excitability testing
(NET) is another test that may come up as an emerging experimental
neurophysiological biomarker of early axonal dysfunction. NET
calculates axonal firing thresholds in response to submaximal and
supramaximal current given through noninvasive electrodes [20].
Thus it can act as a surrogate of axonal membrane dysfunction well
before axonal damage really occurs and nerve conduction studies
(NCS) findings are evident [21,22]. However, there are issues related
to using of this technology such as requirements for specialist
training , equipment and is not widely available. Moreover, NET
is more reliable in motor nerves than sensory nerves , and it does
not give information about the status of small fiber nerves. Hence,
NET needs to be validated before it can be adopted as an alternative
biomarker test for diabetic peripheral neuropathy [20-22]. Neurofilament
light chain (NFL) protein, a marker of axonal degeneration,
is another promising blood biomarker for diabetic neuropathy
[23,24].
In addition to these, advanced imaging techniques manifest
cortical changes that can be utilized as promising biomarkers in
painful DPN. Various strategies have been tried so far to treat diabetic
neuropathy. An expanding literature supports lifestyle-based
therapies for patients with DPN and neuropathy in those who are
in the prediabetes stage. Short-term exercise trials have shown improvement
in gait and function in small sample size studies [25-32].
Studies regarding low-intensity exercises manifested enhanced
quality of life and the resultant decrease in tingling sensations and
pain [33]. Other studies relating to the effects of vitamin supplementation
in diabetic neuropathy: oral alpha lipoic acid [32,33],
vitamin E and D [34-37], and sodium channel blocker have mostly
been inconclusive. In addition to these, few studies have explored
possible role of neuromodulation as a therapeutic strategy for painful
DPN [37,38].
Diabetic Neuropathy has a high prevalence associated with notable
patient morbidity and heavy healthcare costs. There is a need
for developing more effective treatment strategies. Sophisticated
diagnostic criteria and categorization of specific pain subtypes will
help formulate a better clinical trial design. Hence there is a need
for developing biomarkers that prove to be promising in facilitating
earlier diagnosis and formulating suitable clinical trials for such patients
early in the course of the disease.
Aisha Hasan, Khilan MH, Khan A, Hassan MH, Taseer AR, et al. (2020) Comparison of Gabapentin Monotherapy vs. Combination Therapy of Methyl Cobalamin and Gabapentin in Treating Diabetic Neuropathic Pain. J Biol Today's World 9(9): 1-3.
ISSN: 2574 -1241
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