'Fix the Dysfunction' Concept for Mechanism-based Pharmacological Treatment of Neuropathic Pain by Drug

Introduction Treatment of neuropathic pain has been a goal of numerous research projects for the last half century, with overall disappointing results. These poor achievements are in contrast with substantial advancements in the understanding of pain mechanisms, and numerous molecules developed to tackle them. The need to better identify patients likely to respond to treatment comes from the neuropathic pain experts in regards to the pharmacological domain.

The basic assertion of this project is that the pain modulation profile is altered in pain patients toward a pro-nociceptive mode, and that the specific single or multiple dysfunctions of pain modulation that underlie this pro-nociceptivity should be targeted by therapeutic lines that can reverse the modulation back toward eu-nociceptivity.

The aim of this amendment is to demonstrate that pain treatment efficacy for painful diabetic neuropathy can be optimized by individualizing pharmacological treatment choice along 'fix the dysfunction' concept Methods Study design This is a longitudinal double blind non cross over study with parallel groups. There will be three pharmacological treatment arms, one per each treatment: SNRIs duloxetine, Ca++-channels blocker pregabaline and inactive placebo. All treatments will be given to painful diabetic neuropathy patients. All patients will undergo three lab sessions. A uniform assessment will be performed before starting (Session I), and at the end of treatments (Session III). This psychophysical assessment of their pain modulation, physiological assessment that will include resting-state EEG recording along with contact-heat evoked potentials (CHEPs) and assessment of motor cortex excitability, and psychological assessment with pain-related psychological questionnaires. In addition, Session I will also include a clinical examination for the assessment of neuropathy characteristics and symptoms severity.

After one months after the initial Session I, all the patients will undergo the lab session for the assessment their responsiveness to experimental placebo manipulation (Session II), including filling questioners associated with the prediction of placebo effect.

Between sessions I and II the patients will fill an electronic diary in order to evaluate their clinical pain intensity.