Equine

XLR8 Redline is the most comprehensive, easy to use collection of Red Light Therapy available. But what is red light therapy? How does it actually work? What is the real science behind it? Here are some key points, with plenty of studies to back it up.

Excerpts from "Handbook of Photomedicine; Hamblin and Huang"

Mitochondria and Cytochrome C Oxidase

“Cytochrome C Oxidase (CCO) is the terminal enzyme of the respiratory chain in eukaryotic cells, mediating the transfer of electrons from cytochrome c to oxygen. CCO is the most understood photoreceptor and photosignal transducer of the NIR and Red range of light (Karu 1999; Pastore, Greco, and Passarella 2000; Eells et al. 2004: Karu, Pyatibrat, and Kalendo 2004: Karu et al. 2005; Liang et al. 2006), and recently, Tiina I Karu provided a critical review to highlight the role of CcO as an initial photoacceptor of LLLT and ATP as a crucial signaling molecule in biomodulation by LLLT (Karu 2010). Many researchers in past decades have successfully documented the extracellular synthesis of ATP or ATP extrasynthesis in isolated mitochondria and various intact cells under monochromatic light of distinct wavelengths (Karu, Pyatibrat, and Kalendo 1995; Karu 2007). Using ATP as an intercellular signaling molecule provides critical understanding of the complicated mechanisms of photobiomodulation. CcO absorption of light can increase mitochondrial transmembrane potential, ATP, cAMP, and ROS, leading to increased energy availability of the cell and modulation of signal transduction (Karu, Pyatibrat, and Kalendo 1995; Karu, Pyatibrat, and Afanasyeva 2005; Hu et al. 2007; Tafur and Mills 2008). These biochemical and cellular changes in turn lead to macroscopic effects such as increased cell proliferation and accelerated wound healing (Eells et al. 2004; Maiya, Kumar, and Rao 2005; Hu et al. 2007).

Increased mitochondrial energy signals by LLLT were detected in many wavelengths and cell types. Greco et al. (2001) reported that 632.8 nm He-Ne Laser irradiation increased the mitochondrial transmembrane potential in isolated hepatocytes and the uptake of CA2+ by mitochondria. The uptake of CA2+ in mitochondrial membranes stimulates metabolic energy by generating ATP (Greco et al. 2001). The increase in Ca2+ by LLLT was assumed to induce expression of C-Fos because C-Fos upregulation was totally abolished in the absence of Ca2+ (Greco et al. 2001). These findings demonstrate the connection between components of mitochondrial energy signaling and secondary cellular gene expression upon LLLT irradiation…Increased ATP production may be involved in the muscle healing process accelerated by LLLT (Silviera et al. 2009)….

Irradiation caused photobiomodulation to restore homeostasis of injured cells (zunghu, Hawkins, and Abrahamse 2009)….

Clinical applications for LLLT include wound healing, pain attenuation, and various forms of inflammation regulation…

Wound Care:

Skin wound healing represents a series of carefully regulated interrelated processes and events that involve the participation oof many different tissues and cell lineages. The ultimate goal of skin wound healing is to restore its structural contiguity and functionality. In order to understand how LLLT affects each of these processes, a brief overview of the wound healing process is necessary.

Wound healing begins with temporary repair achieved in the form of a fibrin clot that plugs the damage to the tissue and serves as a provisional matrix over and through which the cells can migrate during the repair process. Inflammatory cells, and then fibroblasts and capillaries, invade the clot to form granulation tissue to fill the gap. Macrophages secrete growth factors and signaling elements to direct the process. Meanwhile, the reepithelialization processes begin at the damaged epidermal edges, and epithelial cells migrate forward to cover the denuded wound surface. Myofibroblasts position themselves at the wound edges to draw the wound margins together. Collagen is secreted by fibroblasts and remodels in the process of forming scar tissue. The end result of uncomplicated healing is a fine scar with little fibrosis, minimal if any wound contraction, and a return to near normal tissue architecture and organ function. 

Conceptually, the wound healing process is divided in to three overlapping phases: the inflammatory phase, in which immune cells migrate to the wound immediately after the injury and prepare the wound environment for healing; the proliferative phase, in which new granulation tissue is produced to fill the wound space with increased production of collagen along with reepithelialization to close the wound in parallel with wound contraction; and the remodeling phase, in which continued remodeling of scar tissue matrix results in restoration of wound strength. Experimental studies have shown that LLLT affects all three phases of wound healing.

LLLT was shown to increase keratinocyte Il-la secretion (Gavish et al. 2004: Yu et al. 1996) and stimulate histamine release (Wu et al. 2010) and mast cell degranulation (el Sayed and Dyson 1990), thereby amplifying the initial chemoattractive signal. Increased vasodilation following LLLT was demonstrated as early as two minutes after irradiation in a clinical study (Samoilova et al. 2008). This increase was shown to result from the modulation of nitric oxide, a free radical synthesized by nitric oxide synthase (NOS) that functions as a neurotransmitter on vascular smooth muscle cells as demonstrated by abolishment of the effect after injection of the NOS inhibitor L-NMMA. Indeed, stimulation of NO after LLLT was demonstrated…in human endothelial cells (Chen, Hung, and Hsu 2008).

Inflammatory phase

Arrival of neutrophils at the wound site was accelerated (Gal et al. 2006), and phagocytic (Hemvani, Chitnis, and Bhagwanani 2005; Kupin et al. 1982) and bactericidal (Duan et al. 2001) activities of inflammatory cells were shown to be enhanced following LLLT. This resulted in earlier resolution of the inflammatory phase.

EDEMA: Removing Stagnant tissue fluid

Reduction of regional edema was shown following LLLT in vivo as early as 24 hours after injury (Medrado et al. 2003) and in patients with lymphedema after mastectomy (Lau and Cheing 2009), reflecting acceleration of removal of stagnant tissue fluid. Lievens (1991) found the LLLT restored injured lymph vessels to their original morphologic pattern within a few days without increase in permeability. In contrast, the injured lymph vessels in the control, nonirradiated group regenerated as a network of small lymph vessels that were abnormally permeable.

Proliferative phase:

The Proliferative phase begins 3-4 days after injury and lasts up to 3 weeks in an acute wound. This process consists initially of epithelial cell migration and proliferation. When wound closure is complete, keratinocytes undergo stratification an differentiation to restore the barrier. Inadequate reepithelialization is characteristic of most chronic wounds.

Blood Supply

 For healing to occur, wounds must have adequate blood flow to support the necessary nutrients and to remove the resulting waste local toxins, bacteria, and other debris. LLLT was found to stimulate endothelial cell proliferation directly (Chen, Hung, and HSU 2008; Shindel et al. 2003) or indirectly by upregulating the expression and secretion of VEGF from arterial smooth muscle cells (Kipshidze et al. 2001) and T-lymphocytes (Agaiby et al. 2000). The ability of LLLT to promote antiogenisis in vivo by quantifying vascular density has been reported in a variety of experimental and clinical circumstances. 

Pain

LLLT has both short- and long- term effects in ameliorating pain. The immediate pain relieving effects, which can occur within minutes of application, are affected by neural blockade in peripheral and sympathetic nerves, particularly nociceptors by reduction of muscle spasm, and by reduction in local edema, especially in acute injury. Longer-term effects occurring within days to weeks and lasting months to years are affected by modulation of the inflammatory response and stimulation of tissue healing. These latter effects are the basis of the long term benefits of LLLT, including the preventative effects of LLLT in reducing the progression of acute to chronic pain.

The critical feature in nociceptive pain is the initiation of action potentials by noxious stimuli, the blockade of which will relieve pain. In nociceptive pain, pain is proportional to the stimulus. In acute injury, tissue and cellular disruption result in the formation of “inflammatory soup” that is made of chemical irritants released from disrupted cells and blood. Nerves in the region of local injury become sensitized by these chemicals and proinflammatory neuropeptides, the threshold for activation of these receptors decreases, and patients experience pain. Tissue repair processes are also initiated by this process so that over hours and days, cells such as macrophages and neutrophils migrate to the site of injury to clear cellular debris. At the same time, fibroblasts become active and begin to lay down new tissue to repair the defect. These latter effects also play an important part in long term modulation of pain as tissues heal. Neck pain is representative of many musculoskeletal conditions where pain arises from injury to or arthritis of facet joints, enthesitis of ligaments, spasm of muscles with trigger point formation, as well as nerve impingement from intervertebral disc prolapse (Chow, Barnsley, and Heller 2006), enthesitis such as lateral epicondylitis (Bjordal et al. 2008), and tendinopathies (Bjordal, Couppe, and Ljunggren 2001) will be activated by mechanical and proinflammatory stimuli and are all responsive to LLLT. Kissing spine.

Myofascial Pain

Myofascial pain is defined as chronic pain arising from muscles, fascia, and ligaments. It is associated with muscle pain often as localized areas of tenderness and stiffness. Trigger points are discrete, focal, hyperirritable spots located in a taut band of skeletal muscle that produce local pain and demonstrate reproducible patterns of referred pain when palpated. Myofascial pain and trigger points can occur as a result of microtrauma or chronic postural strain, resulting in chronic spasm and pain. It is proposed that local tenderness in acute muscle pain is caused by peripheral sensitization of local muscle nociceptors (Mense 2003), leading to release and accumulation of inflammatory mediators at this site (Shiah et al. 2008). Central sensitization of dorsal horn neurons from ongoing nociception leads to perpetuation of the pain, spasm cycle, and the persistence of trigger points and myofascial pain.

Several lines of evidence provide support for neurally mediated inhibitory effects, which reduce muscle pain and spasm. Clinical studies have demonstrated the reduction of tenderness and pain by treatment of trigger points (Carrasco et al. 2009; Laasko, Richardson, and Cramond 1997; Snyder-Mackler, Bork, and Bourbon 1986; Snyder-Mackler et al. 1989; Waylonis et al. 1988). Of particular note Is the treatment response, which occurs within the same time frame in which animal studies show conduction block of CMAP’s within 10-20 mins. Moreover, the response on the contralateral side of the body suggest modulation through crossover of second-order neurons in the spinal cord affecting the same segment.

Chronic Pain

Chronic pain is defined as a pain of more than 3 months’ duration. The neurophysiology of persistent pain involves a process of central sensitization in which changes occur within the spinal cord that lower the threshold of afferent stimulation. These changes occur acutely, within 24H of injury, and begin to resolve within days of recovery. In some circumstances, the changes persist rather than resolve, resulting in perpetuation of the pain.

The anti-inflammatory effects of LLLT constitute one of the most important of the pain reliving mechanisms of LLLT. However, neurogenic inflammation constitutes a specific inflammatory process with special relevance to nerve effects of LLLT and pian. The release of proinflammatory neuropeptides, such as substance P, Bradykinin PGE2 from nerve endings, fibroblasts, Schwann cells, and mast cells, that are released locally. This can occur in acute injury or following activation of chronic injury such as Achilles tendinitis. 

Reduction in PGE2 and other inflammatory markers have been demonstrated in cellular, tissue, and in vivo animal and human studies. Cells such as neutrophils and macrophages associated with inflammation also show activation with LLLT, so that LLLT promotes resolution of the inflammatory process necessary for tissue repair. This latter effect occurs over weeks and is the last step in the process of long term pain relief. 

Lymphatic effects

Not all pain relieving effects relate specifically to effects on nerves. Modulation of lymphatic activity is an important component of pain relief. Localized swelling limits mobility and causes impingement of tendons, such as in supraspinatus tendinopathy or around inflamed nerve roots. Swelling is recognized as one of the pathophysiological signs of injury and inflammation, and small reductions in interstitial fluid or swelling in tendons may be sufficient to reduce pain and (improve) mobility.

More generalized swelling as in lymphedema following post-mastectomy and other post cancer surgery is a cause of pain in these clinical situations. Swelling of a limb is associated with pain and heaviness, and taut bands in azillae or broin are painful and restrict mobility. Studies show the efficacy of 904 NM lasers in postmastectomy lymphedema; however, not only is there an immediate effect in reducing swelling but also a delayed benefit occurring several weeks after the initial treatment (Carati et al. 2003; Pillar and Thelander 1995.)

Performance:

Lopes-Martens et al. (2006) reported the effects of LLLT on muscle fatigue in rats. Tibialis anterior muscle fatigue was induced by neuromuscular electrical stimulation and measured the reduction of torque and increase muscle damage from blood levels of creatine kinase, LLLT was applied at a single point of the tibialis anterior before fatigue induction. The results showed a reduced fatigue at a dose of .5 j/cm2 and decreased muscle damage at doses of 1.0 and 2.5 j/cm2.

Vieira et al. (2006) verified the effects of LLLT (780 nm) on energy metabolism related to muscle fatigue in rats trained on a treadmill with load corresponding to the anaerobic threshold for 30 consecutive days. After each workout, rats were irradiated on a single point on the femoral quadriceps, tibialis anterior, soleus, and gluteus maximus. The results showed a greater inhibition of enzymatic activity of lactate dehydrogenase, especially the LDHA isoform pyruvate reductase in the muscles of trained and irradiated rats, also including heart muscle (not irradiated), suggesting there were systemic effects of LLLT.

The results of these previous studies encouraged other researchers to develop more experimental studies in order to identify other interactions between LLLT and muscle tissue subjected to different physical exercises as well as the mechanisms of action of LLLT to reduce the damage and muscle fatigue.

(Sussai et al. 2010) induced fatigue by neuromuscular electrical stimulation. This study investigated the effects of LLLT on CK levels in blood plasma and muscle cell apoptosis of rats after a swimming protocol for induction of muscle fatigue. Compared to the control group, the LLLT group had lower levels of CK and apoptosis 24 and 48 hours after induction of muscle fatigue.

The vast majority of papers involving LLLT and exercise in humans investigated the acute effects on muscle performance in high intensity exercises. Gorgey, Wadee, and Sobhi (2008) applied LLLT in pulsed mode for 5 minutes (low energy) and 10 mins (high energy) on femoral quadriceps before muscle fatigue induction by neuromuscular electrical stimulation. The results showed that LLLT Groups had a lower percentage of muscle fatigue compared to the control group that had statistical significance. There was no significant difference between irradiated groups.