January 2020 – April 2020

Collaborators: Annie Leach, Arshawn Mohseni, Caroline Rogers, Debbie Nya, Faith Aisien

File:Microneedle array comparison with Hypodermic needle.jpg
Image of Microneedles from Wikipedia

This project was for our Introduction to NeuroEngineering course at Georgia Tech. It was split into three phases. In the first phase, we were tasked with selecting a problem area and analyzing the current state of technology for neuro-measurement and neuro-modulation. We decided to focus on sickle cell disease (SCD), specifically on the acute and chronic pain that patients with sickle cell disease suffer from. We found that there are no quantitative, objective measurements of pain for Sickle Cell Disease. For general pain, the most used measurement tool are pain scales. The most common treatment for sickle cell disease patient’s pain is opioid medication (1). However,  However, with the current Opioid crisis, doctors are restricting their prescriptions and being more speculative of patients’ reported pain levels, especially those of African American descent, who comprise the majority of SCD patients (2). This inspired us to have more objective measurement methods so that patients can be trusted by their doctors and receive adequate treatment and better pain modulation methods so that users can have safer, non-addictive treatment.

In the second phase, we focused on pain measurement. We performed extensive research to create three novel pain measurement solutions. Our first solution is a sweat cream, similar to a pH strip, that changes color proportional to the amount of Substance P in the sweat (a biomarker for SCD pain) by reacting with an anti-substance P antibody in the cream to alter the pH. This had limitation in its specificity and reliance on external factors, but is beneficial in providing real-time and visual feedback. Our second solution is wearable Raman Spectroscopy to detect serotonin (a precursor for Substance P) that is amplified through gold nanoparticles. The advantages of this solution is that it is highly specific and allows for quick acquisition, however there is limitation in depth of reading and could be compromised by muscle movement. The third solution is a saliva painmometer that uses a saliva collection stick to collect the patient’s saliva. The saliva then is transferred into a solution of anti-NGF antibody tagged with an immunofluorescence indicator that binds Nerve Growth Factor (a biomarker for SCD pain). A light microscope then takes a picture of the sample and transfers the image to a computer which is then quantified and compared to a baseline reading. This is an objective and individualized solution, but the technology is complex and condensed. Overall, these three solutions are objective and can be used clinically. The accuracy would have to be validated experimentally. These three solutions could provide guidance to clinicians when evaluating their patients’ pain levels.

In the third phase, we transitioned to pain manipulation and management. We again, performed more research, and created three novel solutions. The first solution is a CGRP Receptor Antagonist Topical Drug. CGRP is a nociceptor neuromodulator (3). This application involves modifying current CGRP receptor antagonists drugs to lower the molecular weight and add a foam vehicle. This would lead to rapid absorption of the drug into the skin and lower the pain perception for a SCD patient in crisis. This is a non-invasive, fast acting solution, but requires extensive dosage and efficacy testing. The second solution is a Light Therapy application where a patient sits under a large lamp that emits alternating red and green light which can prevent pain perception, but it is preventative rather than fast-acting. The final solution is a microneedle patch that doses a patient with lidocaine locked in a matrix that is opened when significant levels of HMGB1 (a biomarker for SCD pain crisis) are present to bind to hemicatenated DNA loops and topoisomerase II. This leads to release of drug when the patient is in crisis. This is a painless, minimally invasive, and fast-acting solution, but more research in dosages is necessary.

We then chose one solution to flesh out and write a paper on. This allowed us to identify a series of validation experiments, and identify the advantages and limitations of this solution.

This project showed us the importance of performing research through critical lenses to identify where improvements can be made. It gave us insight to the lives of patients. We were shown how to think outside of the box first and worry about feasibility second to identify the best solution.

Sources:

  1. Pena A. Chronic Pain in Sickle Cell Disease Underpinned by Changes in… Sickle Cell Disease News. https://sicklecellanemianews.com/2019/07/02/chronic-pain-sickle-cell-disease-brain-network-changes/. Published July 2, 2019. Accessed April 27, 2020.
  2. Jenerette, C. M., & Brewer, C. Health-related stigma in young adults with sickle cell disease. Journal of the National Medical Association. 2010; 102(11):1050–1055. doi: 10.1016/s0027-9684(15)30732-x
  3.  Raddant, A., & Russo, A. (2011). Calcitonin gene-related peptide in migraine: Intersection of peripheral inflammation and central modulation. Expert Reviews in Molecular Medicine, 13, E36. doi:10.1017/S1462399411002067

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