Ann Liebert

Protein conformational modulation by photons: A mechanism for laser treatment effects

Responsiveness to low-level laser treatment (LLTT) at a wavelength of 450-910 nm has established it as an effective treatment of medical, veterinary and dental chronic pain, chronic inflammation conditions (arthritis and macular degeneration), wound repair, and lymphoedema, yet the mechanisms underlying the effectiveness of LLLT remain unclear. However, there is now sufficient evidence from recent research to propose an integrated model of LLLT action. The hypothesis presented in this paper is that external applications of photons (through laser at an appropriate dose) modulates the nervous system through an integrated mechanism. This stimulated mechanism involves protein-to-protein interaction, where two or more proteins bind together to facilitate molecular processes, including modification of proteins by members of SUMO (small ubiquitin-related modifier proteins) and also protein phosphorylation and tyrosination. SUMO has been shown to have a role in multiple nuclear and perinuclear targets, including ion channels, and in the maintenance of telomeres and the post-translational modification of genes. The consequence of laser application in treatment, therefore, can be seen as influencing the transmission of neural information via an integrated and rapid modulation of ion channels, achieved through both direct action on photo-acceptors (such as cytochrome c-oxidase) and through indirect modulation via enzymes, including tyrosine hydroxylase (TH), tyrosine kinases and tyrosine kinase receptors. This exogenous action then facilitates an existing photonic biomodulation mechanism within the body, and initiates ion channel modulation both in the periphery and the central nervous system (CNS). Evidence indicates that the ion channel modulation functions predominately through the potassium channels, including two pore leak channels (K2P), which act as signal integrators from the periphery to the cortex. Photonic action also transforms SUMOylation processes at the cell membrane, nucleus and telomeres via signalling processes from the mitochondria (which is the main target of laser absorption) to these targets. Under the hypothesis, these observed biological effects would play a part in the bystander effect, the abscopal effect, and other systemic effects observed with the application of low level laser (LLLT). The implications of the hypothesis are important in that they point to mechanisms that can account for the effectiveness of laser in the treatment and prevention of inflammatory diseases, chronic pain and neurodegenerative disorders.

A Role for Photobiomodulation in the Prevention of Myocardial Ischemic Reperfusion Injury: A Systematic Review and Potential Molecular Mechanisms

Myocardial ischemia reperfusion injury is a negative pathophysiological event that may result in cardiac cell apoptosis and is a result of coronary revascularization and cardiac intervention procedures. The resulting loss of cardiomyocyte cells and the formation of scar tissue, leads to impaired heart function, a major prognostic determinant of long-term cardiac outcomes. Photobiomodulation is a novel cardiac intervention that has displayed therapeutic effects in reducing myocardial ischemia reperfusion related myocardial injury in animal models. A growing body of evidence supporting the use of photobiomodulation in myocardial infarct models has implicated multiple molecular interactions. A systematic review was conducted to identify the strength of the evidence for the therapeutic effect of photobiomodulation and to summarise the current evidence as to its mechanisms. Photobiomodulation in animal models showed consistently positive effects over a range of wavelengths and application parameters, with reductions in total infarct size (up to 76%), decreases in inflammation and scarring, and increases in tissue repair. Multiple molecular pathways were identified, including modulation of inflammatory cytokines, signalling molecules, transcription factors, enzymes and antioxidants. Current evidence regarding the use of photobiomodulation in acute and planned cardiac intervention is at an early stage but is sufficient to inform on clinical trials.

Musculoskeletal physiotherapists' perceptions of non-responsiveness to treatment for cervicogenic headache

Cervicogenic headache (CH) is a debilitating pain problem, estimated to affect 13–17% of the population with chronic headache. Physiotherapy can improve this condition in 75% of patients but the remaining 25% are unresponsive to treatment, and to date researchers have been unable to identify predictors of non-responsiveness. The aim of this study was to seek both consensus and alternative accounts by examining the perceptions of experienced musculoskeletal physiotherapists regarding the features associated with non-responsiveness to treatment in adults and children with CH. A cross-sectional study was conducted (response rate 74%) in which 90 physiotherapists were asked about factors influencing non-responsiveness, using both written responses and Visual Analog Scale ratings, ranging from 0 (strongly disagree) to100 (strongly agree). The means for features in adult CH that physiotherapists rated as being most related to non-responsiveness were: history of severe trauma, 60 SD 27; genetic history of CH or other headache types, 55 SD 24; neural sensitivity, 49 SD 21; minimal presence of upper cervical neck pain and impairment, 55 SD 26; immunological comorbidities, 51 SD 26; and latency of response to treatment, 50 SD 26. These same features were considered to be associated with CH in children, but without the non-responsiveness of adults.

Neuroprotective Effects Against POCD by Photobiomodulation: Evidence from Assembly/Disassembly of the Cytoskeleton

Postoperative cognitive dysfunction (POCD) is a decline in memory following anaesthesia and surgery in elderly patients. While often reversible, it consumes medical resources, compromises patient well-being, and possibly accelerates progression into Alzheimers disease. Anesthetics have been implicated in POCD, as has neuroinflammation, as indicated by cytokine inflammatory markers. Photobiomodulation (PBM) is an effective treatment for a number of conditions, including inflammation. PBM also has a direct effect on microtubule disassembly in neurons with the formation of small, reversible varicosities, which cause neural blockade and alleviation of pain symptoms. This mimics endogenously formed varicosities that are neuroprotective against damage, toxins, and the formation of larger, destructive varicosities and focal swellings. It is proposed that PBM may be effective as a preconditioning treatment against POCD; similar to the PBM treatment, protective and abscopal effects that have been demonstrated in experimental models of macular degeneration, neurological, and cardiac conditions.

Clinical management of cranio-vertebral instability after whiplash, when guidelines should be adapted: A case report

Cranio-vertebral instability (CVI) due to loss of bony or ligamentous integrity is one of the sequelae that may result after a whiplash mechanism injury. Due to the lack of specificity of diagnostic tests, this condition is often missed and the default classification of whiplash associated disorder (WAD) is assigned. This case report describes a 14-year-old boy who was initially classified with WAD II after a rugby injury. He was initially advised to return to usual activity, a treatment recommended in clinical guidelines for WAD. Due to an adverse response to this course of action, his primary carer, a musculoskeletal physiotherapist, continued with facilitating secondary referrals that ultimately led to a specialist physiotherapist. The patient was subsequently found to have CVI arising from a loss of bony integrity due to spina bifida atlanto, a congenital defect in the atlas. Treatment thus was immobilization and stabilization, a treatment usually recommended against in WAD guidelines. The patient recovered and within 8 weeks had returned to school and non-contact sports. This case study, therefore, presents a scenario where current clinical guidelines for whiplash could not be followed, and where pursuing clinical reasoning led to accurate diagnosis as well as safe and tailored management. The case also highlights the integrated roles that primary and specialist health professionals should play in the clinical pathway of care after WAD. As a result, an expanded diagnostic algorithm and pathway of care for WAD are proposed.

Clinical trial involving sufferers and non-sufferers of cervicogenic headache (CGH): potential mechanisms of action of photobiomodulation (Conference Presentation)

Photobiomodulation (PBM) is an effective tool for the management of spinal pain including inflammation of facet joints. Apart from cervical and lumbar joint pain the upper cervical spine facet joint inflammation can result in the CGH (traumatic or atraumatic in origin). This condition affects children, adults and elders and is responsible for 19% of chronic headache and up to 33% of patients in pain clinics. The condition responds well to physiotherapy, facet joint injection, radiofrequency neurotomy and surgery at a rate of 75%. The other 25% being unresponsive to treatment with no identified features of unresponsiveness. In other conditions of chronic unresponsive cervical pain have responded to photobiomodulation at a level of 80% in the short and medium term. A clinical trial was therefore conducted on a cohort of atraumatic patients from the ages of 5-93 (predominantly Neurologist referred / familial sufferers 2/3 generations vertically and laterally) who had responded to a course of PBM and physiotherapy. The CGH sufferers and their non CGH suffering relatives over these generations were then compared for features that distinguish the two groups. Fifty parameters were tested (anthropmetric, movement and neural tension tests included) and there was a noted difference in tandem stance between the groups (.04 significance with repeated measures). As this impairment is common to benign ataxia and migrainous vertigo and in these conditions there is an ion channelopathy (especially potassium channelopathy). A postulated mechanism of action of PBM would involve modulation of ion channels and this is discussed in this presentation.

Prion Protein Signaling in the Nervous System—A Review and Perspective

Prion protein (PrPC) was originally known as the causative agent of transmissible spongiform encephalopathy (TSE) but with recent research, its true function in cells is becoming clearer. It is known to act as a scaffolding protein, binding multiple ligands at the cell membrane and to be involved in signal transduction, passing information from the extracellular matrix (ECM) to the cytoplasm. Its role in the coordination of transmitters at the synapse, glyapse, and gap junction and in short- and long-range neurotrophic signaling gives PrPC a major part in neural transmission and nervous system signaling. It acts to regulate cellular function in multiple targets through its role as a controller of redox status and calcium ion flux. Given the importance of PrPC in cell physiology, this review considers its potential role in disease apart from TSE. The putative functions of PrPC point to involvement in neurodegenerative disease, neuropathic pain, chronic headache, and inflammatory disease including neuroinflammatory disease of the nervous system. Potential targets for the treatment of disease influenced by PrPC are discussed.