Nerve regeneration

Investigators: Rox Anderson, MD
Institution: Wellman Center for Photomedicine, Massachusetts General Hospital

Investigator's profile

Dr. Anderson is a Professor in dermatology at Harvard Medical School, Director of the Wellman Center for Photomedicine; and adjunct Professor of Health Sciences and Technology at MIT. Dr. Anderson has developed many of the non-scarring laser treatments, widely used in medical care. He has also contributed to treatment for vocal cords, kidney stones, glaucoma, heart disease, photodynamic therapy for cancer and acne. He has co-authored over 250 scientific publications and has 65 issued patents. He is a co-founder of many medical device companies including Seventh Sense Biosystems and Follica, Inc. and serves on the advisory panel of many other.

Significance & Background

Figure 1: Coherent Raman images of (a) intact ex vivo rat sciatic nerve, and (b) cold-treated ex vivo rat sciatic nerve showing myelin sheath disruption, lipid droplet formation, and macrophage infiltration (arrowheads).

Opioid addiction is a major, growing crisis in the United States and the developed world. As many as 36 million people worldwide are estimated to abuse opioids, with over 2 million Americans suffering from prescription opioid addiction. Prescribed for both acute and chronic conditions, opioid pain blockers provide temporary relief at the cost of habit formation [1]. Unfortunately, for many conditions including surgical recovery, opioids are amongst the few options available. It is clear that a replacement for opioids is urgently needed that can provide rapid and lasting relief from pain.

Over the past several years, the Anderson group at Massachusetts General Hospital has developed a method that may offer temporary local pain control without the use of drugs through direct modification of nerve conduction. In this paradigm, the myelin sheath that surrounds nerves and enables long-distance conduction of action potentials is temporarily disrupted through a cooling process, leading to a loss of sensation that returns within weeks due to the body's own repair mechanisms. This approach was discovered during the development of cold therapy body sculpting technology, where study participants noted a loss of sensation following the procedure. In a collaboration between the Anderson and Evans laboratories, this loss of sensation was determined to arise due to myelin sheath loss only at the site of cold treatment [2].

Approach

Myelin is a lipid-rich substance that surrounds the axons of nerves and provides insulation to enable the rapid conduction of action potentials. Myelin can be directly visualized (and quantified) with the molecular imaging toolkit known as coherent Raman scattering via its dense concentration of CH2 vibrational modes. Coherent Raman scattering encompasses a set of microscopy methods including coherent anti-Stokes Raman scattering (CARS) and stimulated Raman scattering (SRS) microscopies that have been applied to visualize the structure and dynamics of myelin [3]. The Evans laboratory has developed an existing CARS/SRS microscope for in vivo imaging [4]. In this project, initial studies will examine cold-therapy induced changes in rat sciatic nerves, with CARS/SRS imaging used to visualize ex vivo nerves extracted at select time points post-treatment. These tissues will be processed using standard histopathology, with coherent Raman and immunohistochemistry results used to understand the microscale effects of treatment. As the study continues, the existing coherent Raman imaging system will be used to follow changes in vivo to surgically exposed rat sciatic nerves so as to determine the mechanisms and time course of repair. These measurements will be paired with rat behavioral studies to developed optimized cold therapy methods that can be translated to humans in the near future.

Center offering

The LBRC offers coherent Raman imaging tools via the Evans laboratory at the Wellman Center for Photomedicine that will provide the Anderson team with the imaging tools needed to study myelin disruption and repair. The laboratory also offers a multimodal automated coherent Raman microscope with confocal, multiphoton, and FLIM capabilities. Furthermore, the LBRC provides experience in tissue imaging and quantification, specifically in the areas of neuroscience. Image analysis toolkits developed by the members of the LBRC will be used to analyze coherent Raman imaging data and extract quantitative information including parameters such as myelin concentration, myelin structure, and axon size.

References

  1. "Drug-activation of brain reward pathways," Drug and Alcohol Dependence, 1998. [ Link ]
  2. "Transient Alterations of Cutaneous Sensory Nerve Function by Noninvasive Cryolipolysis," Journal of Investigative Dermatology, 2015. [ Link ]
  3. "Coherent anti-stokes Raman scattering microscopy: chemical imaging for biology and medicine," Annual Review of Analytical Chemistry, 2008. [ Link ]
  4. "Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy," PNAS, 2005. [ Link ]