Background: Worldwide, the prevalence of diabetes mellitus (DM) and its chronic complications
are reaching epidemic proportions. By 2045 DM expected to affect 629 million persons.
Diabetic neuropathy is one of the most common complications of DM and is actually the set of
heterogeneous clinical forms. Among diabetic neuropathies, generalized, focal or multifocal
forms are distinguished. The most typical and most common form (up to 80% of cases is
sensory-motor polyneuropathy. It has recently been redefined as a length-dependent symmetric
sensory-motor polyneuropathy attributable to metabolic and microvascular alterations
following exposure to chronic hyperglycemia and cardiovascular risk cofactors. Painful
diabetic peripheral neuropathy (PDPN) may be considered a variant; about 15-25% of patients
have painful diabetic polyneuropathy.
According to the definition of neuropathic pain of the International Association for the
Study of Pain (IASP), PDPN is considered as asymmetric sensory-motor polyneuropathy chronic
in which neuropathic pain has been present, for at least 3 months, as direct consequence
abnormalities of the peripheral somatic-sensitive system following diabetic pathology.
Sensory symptoms are more evident than motor symptoms; which is appear in the most distal
portions of the limbs and progress proximally according to a "glove" or "sock" distribution
associated with paresthesias and dysesthesias. The clinical symptoms are related to the type
of nerve fiber involved and typically there are "positive" (tingling, burning, pain,
allodynia) or "negative" sensory symptoms (loss of sensitivity, numbness). The involvement of
small sensitive fibers causes a reduction in thermal sensitivity and pain and this, in turn,
contributes to the deficits in tactile and proprioceptive sensitivity to increase the risk of
a foot injury.
The PDPN is associated with negative repercussions on the quality of life (QoL), activities
of daily livings, sleep disorders, and is the major determinant of depressive symptoms in
patients with PDNP. In fact, depression and sleep disturbances play a negative prognostic
role in the general and diabetic population, and sleep disturbances are associated with
glycated hemoglobin levels higher than 0.35% in type 2 diabetes. The presence of PDPN
determines an increase in the use of medical care and social costs, both directly related to
treatments, and indirect secondary to the reduction of working capacity. The presence of
chronic pain of any nature increases the risk of difficulties in the self-management of
diabetes, in relation to taking therapy, physical activity, adherence to the diet, foot care
and even glycemic self-monitoring.
Transcranial Direct Current Stimulation (tDCS) has shown promising results for the treatment
of chronic pain in several types of diseases, being a good and non-invasive alternative to
treat pain in PDPN patients. Also, based on studies that showed changes in the brain activity
of chronic pain patients and on the difficulties faced to treat PDPN, there is a need to
conduct clinical trials using new techniques, such as neuromodulation, to help these patients
to control their pain. Therefore, tDCS emerges as a new tool to be coupled with other
effective treatments already used for these patients.
The dorsolateral prefrontal cortex (DLPFC) is a functionally and structurally heterogeneous
region as well as a key area of numerous brain networks involved in the processing of
cognition effect. Numerous studies have shown that some chronic pain syndromes are associated
with a reduction in the volume of the gray matter of DLPFC. Some studies show that pain
relief manages to reverse these structural changes PDPN. Moreover, previous studies reported
that DLPFC stimulation induces a significant analgesic and antidepressant effect.
Hypothesis: The investigators believe that neuromodulation by tDCS over the left DLPFC would
decrease the pain intensity and improve the general quality of life in patients with PDPN.
Objectives: general PURPOSE Investigate if anodal tDCS over left DLPFC has analgesic effects
in patients with PDPN.
Specifics purposes 1- Evaluate the tDCS effects over pain intensity; 2- Evaluate if tDCS has
any effect on sleep quality, depression, anxiety, and quality of life.
Randomization: The subjects will be allocated consecutively to randomization as an
intervention order using the tool from the randomization.com website (Dallal GE,
http://www.randomization.com). The investigators will use the second generation suggested for
crossover studies.
Data Collection Procedure: All subjects will be treated using two different interventions
(groups respecting the washout period of six weeks to avoid residual effects. The
intervention order will be determined by randomization per group of interventions. Subjects
will be contacted by phone and asked if they want to participate in the study. Those who wish
to participate and qualify according to the selection criteria after completing the
pre-screening questionnaire will be scheduled after reading and signing the consent form (2
copies). During the second visit, all clinical and neurological assessments will be performed
before and after tDCS stimulation phase. Each patient will be clinically and neurologically
assessed before and after the stimulation, allowing data to be collected 4 times (T0, T1, T2,
and T3).
tDCS protocol: Group Real tDCS: The participant will receive anodal tDCS over the left DLPFC
and the reference electrode will place over the right forearm. The stimulation intensity will
be 2mA DC delivered for 20 min (30 s step-up ramp, 30 s step-down ramp), repeated six times,
during two weeks (Mon, Wed, Frid).
Group sham tDCS: Identical to the real tDCS, except the participants will only receive the
initial 30 seconds of ramp-up, after which the current will be set to 0 for the remainder of
the 20 minutes.