Novel devices and strategies to investigate and counteract pain: an engineer’s point of view on pain and how to fight against it

Pain is a gift; it is a fundamental adaptive mechanism to protect ourselves from injuries and illnesses [1]. While usually pain is perceived as debilitating and intolerable and researchers are focusing on how to suppress it, its presence has a great survival value, which becomes evident in its absence. Contrary to the common belief, insensitivity to pain is a curse, which sometimes is an ill-fated consequence of some conditions, such as alcoholism, multiple sclerosis, diabetes and leprosy [2]. Pain warns us of dangers, impeding us to continue adding insult to an injury causing more serious issues; it forces us to rest and protect the affected body part until the latter has recovered completely. As such, pain represents an "unpleasant sensory and emotional experience" but "associated with actual or potential tissue damage" [3], thus necessary to avoid further repercussions. When a high-intensity stimulus that can damage tissues is applied onto the human skin, it activates pain receptors [4], called nociceptors; information reaches the brain through myelinated A and un-myelinated C nerve fibers and the pain is experienced. If pain is certainly a gift, complications arise when its natural mechanisms do not perform correctly and the unpleasant painful sensations become incessant, interfering drastically with the person’s quality of life. This is not a rare event: as an example, more than 100 million adults in the United States only are affected by chronic pain. In such cases, pain loses its role as a warning against more critical injuries and simply becomes a medical problem, requiring medical treatment. Costs of these treatments are not negligible: they range from $560 to $635 billion of US dollars per year, combining the health care cost and the productivity estimates [5]. Therefore pain has to be investigated, to be better understood and counteracted, if necessary. Easy? Not at all: pain is difficult to ascertain, is primarily assessed by means of self-report [6] and experiments on pain suffer from a lack of reproducibility and accuracy. The result is that many relevant neuro-physiological aspects on pain still remain unclear. Here is where the engineer work becomes essential: medicine needs engineering to design, develop and implement reliable and precise devices whose features help pain research. Furthermore, when possible, the engineer should propose solutions that are inexpensive, portable, easy-to-assemble and customizable to suit diverse experimental requirements, ready to be employed into different researches. A complex challenge, without a doubt, but fundamental: the reader will find throughout this thesis, final report of my PhD in Electronic Engineering, a dissertation on the development of brand new devices and strategies to study and counteract the feeling of pain. Particularly, this thesis is made of two distinct engineering projects, devoted to these two aspects respectively. i ii Part I - Pain Counteraction: PROVIRT PLP project has the aim to improve the rehabilitation of upper limb amputees who suffer from Phantom Limb Pain syndrome, a chronic pain condition, with a technology based on pattern recognition and virtual reality. A promising discover made by Ramachandran [3] showed how restoring the visual feedback of the amputated limb may have a primary importance in the pain counteraction, thus I implemented a device to maximise such illusion. PROVIRT PLP is able to read surface electromyographic signals from the amputee’s stump and coherently convert them into the movement of an avatar in a virtual reality environment. This part describes the project requisites, the design and implementation of the electronics, the observation regarding the classifiers and the pattern recognition stage and the software application that commands the virtual reality module. The system is then further improved by the means of three experimental in-vivo tests, namely Test A - Optimization of EMG-based hand gesture recognition: Supervised vs. unsupervised data preprocessing on healthy subjects and transradial amputees (published as [7]), Test B - Evaluating the influence of subject-related variables on EMG-based hand gesture classification (published as [8]) and Test C - Tuning parameters and performance evaluation. The project has been funded by INAIL (Italian government agency for the insurance against work-related injuries) and can be considered a successful compromise between gesture/intention of movement classification accuracy and ease of use for both health professionals and amputees. To date, Test D - Therapy effectiveness that will eventually shed some light on PROVIRT PLP suitability for PLP counteraction is ongoing, with promising partial results. Part II - Pain Investigation: PUSH project has the aim to define objective measures of pain, by means of robust and consistent patterns of noxious stimuli and innocuous touch. The project wants to develop a device, able to allow for reliable non-invasive investigation of the peripheral and central mechanisms related to the sense of pain, towards the definition of biomarkers for its quantitative assessment. Since fMRI is the standard tool in advanced brain research, PUSH is developed to be completely MR-compatible. This part describes the idea of a pneumatic-driven system to elicit pain, the design and implementation of the electronics, the characterization of the system and a fMRI in-vivo experiment on an adult volunteer to validate it. The project can be considered as a brand new interesting prototype for any kind of fMRI- and EEG-based work on painful mechanical stimulation, and a technical paper that describes its details is published as [9]. This work has been funded by the Department of Bioengineering, Imperial College of Science, Technology and Medicine, London, UK, the Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK and the Centre for the Developing Brain, Kings College London, St Thomas’ Hospital, London, UK. Support for this research is by the EU-FP7 grants CONTEST (ITN-317488), BALANCE (ICT-601003), Symbitron (ICT-661626) and EU-H2020 grant CogIMon (ICT-23-2014). Summarizing, this research work is a step forward towards a strict cooperation between engineers and medical doctors, in the perspective of further advances in the understanding and the counteracting of the feeling of pain in humans. Two engineering devices, PROVIRT PLP and PUSH, have been developed to address and solve medical challenges, hoping they will be even a small puzzle piece in helping people achieve a better quality of life.