Red LED photobiomodulation reduces pain hypersensitivity and improves sensorimotor function following mild T10 hemicontusion spinal cord injury

Abstract

BackgroundThe development of hypersensitivity following spinal cord injury can result in incurable persistent neuropathic pain. Our objective was to examine the effect of red light therapy on the development of hypersensitivity and sensorimotor function, as well as on microglia/macrophage subpopulations following spinal cord injury.MethodsWistar rats were treated (or sham treated) daily for 30 min with an LED red (670 nm) light source (35 mW/cm2), transcutaneously applied to the dorsal surface, following a mild T10 hemicontusion injury (or sham injury). The development of hypersensitivity was assessed and sensorimotor function established using locomotor recovery and electrophysiology of dorsal column pathways. Immunohistochemistry and TUNEL were performed to examine cellular changes in the spinal cord.ResultsWe demonstrate that red light penetrates through the entire rat spinal cord and significantly reduces signs of hypersensitivity following a mild T10 hemicontusion spinal cord injury. This is accompanied with improved dorsal column pathway functional integrity and locomotor recovery. The functional improvements were preceded by a significant reduction of dying (TUNEL+) cells and activated microglia/macrophages (ED1+) in the spinal cord. The remaining activated microglia/macrophages were predominantly of the anti-inflammatory/wound-healing subpopulation (Arginase1+ED1+) which were expressed early, and up to sevenfold greater than that found in sham-treated animals.ConclusionsThese findings demonstrate that a simple yet inexpensive treatment regime of red light reduces the development of hypersensitivity along with sensorimotor improvements following spinal cord injury and may therefore offer new hope for a currently treatment-resistant pain condition.

Photobiomodulation and different macrophages phenotypes during muscle tissue repair

“…In vivo experiments have demonstrated that PBM (808 nm) can shift the phenotype of brain microglial polarization from the pro‐inflammatory phenotype (M1) to the anti‐inflammatory (M2) phenotype after ischemic stroke, promoting cortical neurogenesis 35. There are also reports of the ability of red and NIR PBM to modulate the macrophage/microglia phenotype, leading to a predominance of M2 macrophages associated with better recovery of the spinal cord and peripheral nerves after a spinal cord injury36, 37 and spared nerve injury,38 respectively.…”

Red-light (670 nm) therapy reduces mechanical sensitivity and neuronal cell death, and alters glial responses following spinal cord injury in rats

“…Laminectomy was performed at the T10 vertebra where the dura mater and arachnoid were removed. A 10 g weight drop from 25 mm above the spinal cord was used to induce a hemi-contusion on the right side of the spinal cord 21, 24 . Sham-injured animals underwent the same surgical procedures without the impaction.…”

“…A commercially available LED array (75 mm 2 ) that provided light at 670 ± 15 nm with a measured irradiance of 35.4 ± 0.05 mW/cm 2 (WARP 75A; Quantum Devices, Inc) was placed directly above a Perspex box for light-treated animals (SCI+670 and sSCI+670 groups). Details of the spectral features and irradiance measurements of this light source has been previously described 21 . The treatments were delivered for 30 mins per day (63.7 ± 0.09 J/cm 2 per session) to the dorsal surface of the animal.…”

“…Nitric oxide (NO), which is mainly derived from microglial inducible NO synthase (iNOS), has been shown to modulate long-term potentiation of C-fibres that eventually leads to hypersensitivity 17 . Several studies have shown that by altering some of these key inflammatory mediators, it might be possible to stall the development of NP, or even depress its severity following SCI 18-21 .…”

“…Wavelengths between 630 nm and 830 nm have been demonstrated to reduce glial activation and reduce secretion of inflammatory cytokines in different injury models, including SCI 22, 23 . We have previously established that 670 nm treatment in spinal cord injured rats reduces microglia/macrophage activation and alleviates mechanical hypersensitivity at 7-days post-injury (dpi) 21 . In the present study, we examined the effects of 670 nm treatment during the subacute phase of recovery (prior to 7-dpi) following SCI on: i) the development of mechanical hypersensitivity; ii) myelination and neuronal apoptosis; and iii) astrocyte and microglia/macrophages presence in the spinal cord and their associated IL1β and/or iNOS expression in the white matter tracts.…”