Suppression of matrix degradation and amelioration of disc degeneration by a 970-nm diode laser via inhibition of the p38 MAPK pathway in a rabbit model.

Intervertebral disc degeneration (IVDD) mainly manifests as an imbalance between the synthesis and degradation of cellular and extracellular matrix (ECM) components. The cytokine interleukin (IL)-1ß-induced inflammatory response of intervertebral discs causes ECM degradation. The aim of this study was to investigate the effects of a 970-nm diode laser therapy (DLT) on inflammatory cytokine IL-1ß and ECM degradation proteinases in nucleus pulposus (NP) tissues in a puncture-induced rabbit IVDD model. Thirty-six New Zealand white rabbits were randomly divided into six groups: the normal group, IVDD group, laser group, sham laser group, IVDD + anisomycin (p38MAPK signaling pathway agonist), and laser + anisomycin group. Effects of laser on IVDD progression were detected using radiographic and magnetic resonance imaging. Hematoxylin and eosin, Alcian blue, safranin O-fast green staining, western blotting, and immunohistochemistry staining were performed for the histological analysis and molecular mechanism underlying protection against puncture-induced matrix degradation in NP tissues by DLT. DLT reduced the degree of disc degeneration in the gross anatomy of the disc and increased the T2-weighted signal intensity of NP. Inflammatory cytokine IL-1ß levels in the disc were significantly reduced after DLT suppressed the matrix-degrading proteinases MMP13 and ADAMTS-5 and upregulated the protein expression of collagen II and aggrecan. Moreover, it inhibited the p38MAPK signaling pathway in NP tissues in a puncture-induced rabbit IVDD model. DLT reduced puncture-induced overexpression of inflammatory cytokines, mainly IL-1ß, thus inhibiting matrix degeneration of NP tissues and ameliorating IVDD. This may be related to inhibition of the p38 MAPK signaling pathway.

Biological non-ablative repair of lumbar discs by transforaminal intradiscal laser irradiation: MRI quantitative analysis of the effects-preliminary report.

Degenerative disc disease is a significant reason for low back pain. Low-level laser irradiation (LLLI) of cartilage results in its reshaping and combines with regenerative reaction. A certain pattern of lumbar disc irradiation induces healing reaction and formation of new cartilage. Quantitative MRI analysis of regenerative response of the cartilage is the subject of this investigation. Fifty-one lumbar discs of 28 patients with discogenic low back pain underwent irradiation with 1.56-µm Er fiber laser (1.2 W). Quantitative MRI analysis is performed in STIR regime within 0.93-14.80 months. Signal intensity is estimated from irradiated discs and control measured from adjacent non-irradiated discs and vertebral bones. T2 WI follow-up is performed within a long period (up to 5 years) in selected cases. The mean value of MRI signal intensity from the irradiated discs increased by 14% (p <<< 0.001). The control bone measurement revealed no difference in signal intensity (p = 0.83). The adjacent non-irradiated discs slightly increased their signal (p < 0.05). T2 WI follow-up within 5 years revealed a steady increase of the signal and the irradiated discs healing. LLLI of degenerated intervertebral discs by 1.56-µm Er fiber laser produces increase of MRI disc signal within the first year after treatment that confirms regenerative response of the disc and could lay in the basis of clinical improvement. Further assessment on the effect is mandatory.

Effects of photobiomodulation on annulus fibrosus cells derived from degenerative disc disease patients exposed to microvascular endothelial cells conditioned medium.

Intervertebral disc (IVD) degeneration with chronic low back pain is associated with neo-vascularisation into the deeper IVD regions. During this process, endothelial cells (ECs), which are primarily responsible for angiogenesis, interact with the adjacent annulus fibrosus (AF) cells, which are the first line of defence against the invasion of vascular structures into deeper IVD regions. However, the accumulation of inflammatory and catabolic enzymes that results from this interaction promotes matrix degradation and an inflammatory response. Thus, regulating the production of these mediators and catabolic enzymes could ameliorate IVD degeneration. Photobiomodulation (PBM) therapy is a non-invasive stimulation known to have biologically beneficial effects on wound healing, tissue repair, and inflammation. Here, we examined the effects of PBM, administered at various wavelengths (645, 525, and 465 nm) and doses (16, 32, and 64 J/cm2), on EC-stimulated human AF cells. Our results show that PBM selectively inhibited the EC-mediated production of inflammatory mediators, catabolic enzymes, and neurotrophins by human AF cells in a dose- and wavelength-dependent manner. These results suggest that PBM could be a superior and advanced treatment strategy for IVD degeneration.

Perilesional photobiomodulation therapy and physical rehabilitation in post-operative recovery of dogs surgically treated for thoracolumbar disk extrusion.

BACKGROUND: Recent studies have reported contrasting results of the effects of laser therapy on post-operative intervertebral disk herniation, with a lack of evidence-based advantages of this modality within a rehabilitation protocol. The aim of this study was to report the clinical effects of photobiomodulation therapy within a post-operative rehabilitation protocol in dogs submitted to surgery for thoracolumbar disk extrusion. Twenty-four dogs were included in the study (12 dogs treated with laser therapy and rehabilitation protocol and 12 dogs treated with same rehabilitation protocol but without laser therapy). RESULTS: All dogs treated with laser therapy showed improved neurological status (Modified Frankel Score more than 3 within 30 days of physiotherapy starting) if deep nociception on admission was maintained (P = 0.04). However, Kaplan-Meier analysis did not show any statistical difference in time to regain ambulatory ability, although there was a tendency for a shorter mean time of 14.2 ± 8.55 days in the laser group versus 24 ± 18.49 days in the no laser group. CONCLUSIONS: The use of laser therapy in the post-operative rehabilitation of dogs affected by intervertebral disc extrusion and submitted to surgery for spinal decompression could help improve their neurological status.

Beyond the Laboratory, Into the Clinic: What Dogs with Disk Disease Have Taught Us About Photobiomodulation for Spinal Cord Injury.

BACKGROUND: For spinal-cord-injured (SCI) patients, integrative medicine approaches such as photomedicine and acupuncture can renew hope and offer previously unrecognized ways to help regain function and improve quality of life. OBJECTIVE: By understanding the mechanisms of action that these two modalities share, practitioners can better target specific attributes of spinal cord pathophysiology that are limiting recovery. Naturally occurring intervertebral disk disease (IVDD) in dogs affords unparalleled translational opportunities to develop treatment strategies involving photobiomodulation and acupuncture. CONCLUSIONS: Insights derived through clinical trials of dogs with IVDD have the potential to raise the standard of care for both human and canine SCI patients.

Photobiomodulation on human annulus fibrosus cells during the intervertebral disk degeneration: extracellular matrix-modifying enzymes.

Destruction of extracellular matrix (ECM) leads to degeneration of the intervertebral disk (IVD), which is a major contributor to many spine disorders. IVD degeneration is induced by pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß), which are secreted by immune cells, including macrophages and neutrophils. The cytokines modulate ECM-modifying enzymes such as matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in human annulus fibrosus (AF) cells. The resulting imbalance in catabolic and anabolic enzymes can cause generalized back, neck, and low back pain (LBP). Photobiomodulation (PBM) is known to regulate inflammatory responses and wound healing. The aim of this study was to mimic the degenerative IVD microenvironment, and to investigate the effect of a variety of PBM conditions (wavelength: 635, 525, and 470 nm; energy density: 16, 32, and 64 J/cm(2)) on the production of ECM-modifying-enzymes by AF cells under degenerative conditions induced by macrophage-conditioned medium (MCM), which contains pro-inflammatory cytokines such as TNF-α and IL-ß secreted by macrophage during the development of intervertebral disk inflammation. We showed that the MCM-stimulated AF cells express imbalanced ratios of TIMPs (TIMP-1 and TIMP-2) and MMPs (MMP-1 and MMP-3). PBM selectively modulated the production of ECM-modifying enzymes in AF cells. These results suggest that PBM can be a therapeutic tool for degenerative IVD disorders.

Identification of intervertebral disc regeneration with magnetic resonance imaging after a long-term follow-up in patients treated with percutaneous diode laser nucleoplasty: a retrospective clinical and radiological analysis of 14 patients.

PURPOSE: The aim of this study was to demonstrate regeneration of intervertebral discs undergoing laser therapy with sagittal relaxation time (T2) mapping after a long-term follow-up. MATERIALS AND METHODS: Fourteen patients (9 men, 5 women; age range 20-57 years; mean age 36.5 years) treated with percutaneous 908-nm wave-length diode laser nucleoplasty for lumbar disc prolapsus at our clinic between January 2006 and June 2009 were studied. For the application of laser nucleoplasty in the past, patients who did not have central canal stenosis and/or lateral stenosis, sequestered disc fragment, operation scars and bleeding disorders were selected. The intervertebral disc levels undergoing laser therapy were L3-L4 (n = 2) or L4-L5 (n = 12). Patients were called for follow-up visits after a maximum 6-years (n = 2) or a minimum 3 years (n = 3) with a mean of 4.4 years. The patients' clinical status for leg pain was evaluated according to the visual analog scale (VAS) and subsequently, a lumbar magnetic resonance imaging was performed. Sagittal T2 mapping was performed for the intervertebral discs undergoing laser nucleoplasty. We analyzed the relationship between T2 in the regions of interest (ROIs), which is known to correlate with changes in the composition of intervertebral discs, and the degree of degeneration determined using the Pfirrmann grading system and VAS of patients. RESULTS: On the basis of the evaluation of the results of intervertebral discs in all patients, there was a significant increase in T2 in the anterior NP (ROI 2, +10.3 ms; p < 0.05). A significant increase was noted in T2 in the middle NP (ROI 3, +24.6 ms; p < 0.001). The most significant increase was recorded for the posterior NP (ROI 4, +28.6 ms; p < 0.001). No significant decrease was found in T2 in the anterior and posterior AF (ROI 1, -1.5 ms; p = 0.925; ROI 5, -0.1 ms; p = 0.683). According to the Pfirrmann grading system, disc degeneration grades before laser therapy were recorded as grade III (n = 6) and grade IV (n = 8) whereas disc degeneration grades after laser therapy were found to be grade I (n = 6) and II (n = 8). A significant decrease was noted in Pfirrmann grades of disc degeneration after laser therapy (p < 0.0005). CONCLUSIONS: In this study, there was a prolongation of T2 indicating regeneration in the nucleus pulposus after laser therapy and these results were found to be consistent with VAS measurements after a long-term follow-up. This study, which demonstrates the quantitative efficacy of laser therapy, indicates that MRG can be more effectively used in the future.