Effects of Red Light Treatment on Spinal Cord Injury

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Effects of Red Light Treatment on Spinal Cord Injury ( effects-red-light-treatment-spinal-cord-injury )

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CHAPTER 5 measure of functional damage in that pathway when compared to the contralateral nerve (the uninjured side), which provides a relative control response. Spinal cord injured animals display significantly decreased gracile nuclei response magnitudes and significantly increased latency at 7 days compared to normal animals (Figure 3.3). These sensory deficits could be due to Wallerian degeneration and demyelination respectively (Section 1.1.1.1), and may be indicative of oligodendrocyte apoptosis in the spinal cord (Crowe et al., 1997). With 670 nm treatment, these sensory deficits are restored to a level similar to normal animals. This is the first evidence that 670 nm treatment, or photobiomodulation in general, can improve non-pain related sensory recovery following spinal cord injury. This sensory restoration by red light treatment might be related to reduced cell death (Section 5.2.1.3). Future studies could investigate the effects of 670 nm on oligodendrocyte apoptosis, in addition to axonal degeneration and demyelination. As these processes are ongoing, future studies could also focus on the long-term sensory changes. Pain Spinal cord injury induces mechanical hypersensitivity for at least the first 7 days in rats (Chapter 3 and Chapter 4). The percentage of hypersensitive animals is similar to that in the clinical settings (Dijkers et al., 2009). It is not yet clear why some develop hypersensitivity, and others do not. However, evidence suggests that following spinal cord injury, anatomical and physiological changes at the spinal and/or supraspinal levels may result in pain (Section 1.1.1.2). With 670 nm treatment, the incidence of developing hypersensitivity is significantly reduced for the first 5 days (Figure 4.3) and the mechanical sensitivity at 7 days in hypersensitive animals is also reduced (Figure 3.2). Cytokines and free radicals secreted by M1 microglia/macrophages, e.g., IL1β and NO, have been shown to enhance synaptic strength and induces LTP in the spinal cord (Clark et al., 2015; Ikeda et al., 2006), and is proposed to result in pain development following spinal cord injury (Hulsebosch et al., 2009). Therefore, the reduction of hypersensitivity incidence by 670 nm treatment could have resulted from the decrease in the M1 microglia/macrophage population (Figure 3.6), especially the iNOS+ M1 microglia/macrophage (Figure 4.10). It is therefore worthwhile to investigate the expression of these inflammatory cells in the hypersensitive animals and the effects of 670 nm treatment, and compare those to animals that do not develop hypersensitivity. It remains unclear how 670 nm treatment reduces mechanical sensitivity in hypersensitive animals only at 7 days. It is possible that at this later time point, a different mechanism is involved, or that it takes at least 7 days to develop at a level that can be sufficiently detected. It has been reported that axonal sprouting occurs around 7 days post-injury (Rust and Kaiser, 2017) and that inappropriate intraspinal sprouting may lead to the development of pain following spinal cord injury (Christensen and Hulsebosch, 1997). The effect of red light during long-term recovery on axonal sprouting in hypersensitive animals would provide useful insight 119

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