SA JOURNAL OF DIABETES & VASCULAR DISEASE
CURRENT TOPICS
VOLUME 7 NUMBER 4 • NOVEMBER 2010
139
Recent advances in the pharmacological management of
painful diabetic neuropathy
SOLOMON TESFAyE, DINESH SELvARAJAH
Abstract
P
ainful diabetic peripheral neuropathy (DPN) affects
10–26% of all diabetic patients and continues to pose
significant clinical/treatment challenges. Pharmacologi-
cal treatment of painful DPN includes tricyclic antidepres-
sants (TCAs), selective serotonin nor-adrenaline reuptake
inhibitors (SNRIs), selective serotonin reuptake inhibitors,
anticonvulsants, opiates, the antioxidant alpha lipoic acid,
membrane stabilisers, topical capsaicin etc. Over the past
five years many compounds have undergone clinical trials
and new agents have immerged. Current first-line therapies
for painful DPN are a TCA, SNRI (such as duloxetine) or anti-
convulsants (such as pregabalin or gabapentin), taking into
account patient co-morbidities and cost. On the basis of cost
NICE has recently recommended the use of TCAs before the
other first-line agents of painful DPN. Second-line therapies
include opiates such as tramadol, morphine and oxycodone.
Keywords:
diabetic peripheral neuropathy, DPN, pain therapy
Introduction
Up to 50% of all diabetic people with long duration diabetes have
polyneuropathy. It is a major cause of morbidity and is associated
with increased mortality. DPN is the most common presentation.
We have known for some time now that poor blood glucose control
is an important risk factor for the development of DPN
1
and several
recent studies have demonstrated that cardiovascular risk factors,
including hypertension, dyslipidaemia, smoking and obesity also
appear to be independent risk factors.
2-4
Around a third of patients with DPN present with painful
symptoms. Pain is the most distressing symptom of DPN and the
main reason for seeking medical attention.
5
Affected patients often
have a progressive build-up of unpleasant sensory symptoms (Table
1) including tingling or ‘pins and needles’ (paraesthesae); and/or
pain characteristic of burning, shooting (like ‘electric shock’ down
the legs), lancinating (stabbing or knife like) and deep aching quality.
Some patients may experience evoked pains such as allodynia
(a non-painful stimulus perceived as painful) and hyperaesthesia
(a slightly painful stimulus perceived as being very severe). With
advanced disease, when the pain is well established in the lower
limbs, the pain can extend to the upper limbs.
Painful DPN has a major impact on quality of life as the majority
of patients experience pain on a constant daily basis.
6
It has a
major negative impact on sleep, the ability to work effectively
(functionality), mood, recreational activities, mobility and general
enjoyment of life. For example, some patients may be in a constant
state of tiredness because of sleep deprivation,
7
while others are
unable to maintain full employment. In those with severe painful
DPN there may be marked reduction in exercise threshold so as
to interfere with basic daily activities. Perhaps not surprisingly,
depression and anxiety are common features of those with
moderate to severe painful DPN.
7
Epidemiology of painful DPN
There are only a few studies looking at the prevalence of painful DPN
specifically, and they report a prevalence rate of 10–26%, reflecting
differing criteria used to diagnose neuropathic pain.
8-10
Partanen
et
al
. reported that 6% of newly diagnosed type 2 diabetic subjects
presented with pain at diagnosis (vs 3% of non-diabetic controls),
and this had increased to 20% 10 years later.
8
In a study involving
350 diabetic patients and 344 age and sex-matched non-diabetic
control subjects in the urban Liverpool area, the prevalence of
painful DPN, assessed by structured questionnaire and examination,
was estimated at 16%.
9
Sadly, in the patients with painful DPN
Correspondence to: Prof Solomon Tesfaye
University of Sheffield, Royal Hallamshire Hospital, Glossop Road, Sheffield,
S10 2JF, UK.
Tel: +44 (0)114 271 2709; Fax: +44 (0)114 271 3915
E-mail:
S Afr J Diabetes Vasc Dis
2010;
7
: 139–142.
Abbreviations and acronyms
DPN
diabetic peripheral neuropathy
EMEA
European Medicines Agency
FDA
Food and Drug Administration
5-HT
5-hydroxytriptamine
NICE
National Institute for Health and Clinical Excellence
NNT
number needed to treat
TCA
tricyclic antidepressant
SNRI
selective serotonin noradrenaline reuptake inhibitor
Table 1.
Symptoms of DPN
Sensory symptoms
• numbness (dead feeling)
• paraesthesia (pins and needles)
• pain (burning, stabbing, shooting, deep aching)
• evoked pain
allodynia
hyperaesthesia
• inability to identify objects in hands
• sensory ataxia
Motor symptoms
(usually in advanced disease)
• difficulty climbing stairs
• difficulty lifting objects
• difficulty handling small objects
