By James Carroll, Founder and CEO THOR Photomedicine Ltd
You probably do not need much reminding about America’s opioid crisis; the numbers are huge. CDC figures state that there are 100 million adults in the United States (US) affected by chronic pain, and over $600 billion a year are spent on health care costs related to pain and lost productivity. There were over 49,000 deaths associated with opioids in 2017—19,000 of which came from prescribed opioids.
According to the Assistant Secretary for Health, Admiral Brett Giroir, “you cannot solve the opioid crisis without solving the pain crisis”.
What is photobiomodulation (PBM), and how does it help solve the opioid crisis?
PBM is something you have seen on Star Trek.
On Star Trek, when somebody was injured, the doctor would aim a low-intensity laser beam at the injury, and the wounds would heal instantly! That is photobiomodulation (PBM). The effects are not as fast as shown on TV, but the idea is the same: light is shone on people, and they get better more quickly.
PBM is a non-thermal light therapy that reduces the underlying causes of pain: trauma, inflammation, degenerative joints, and neuropathies. PBM utilizes low-intensity lasers and LED devices in the red and near-infrared spectrum (600–1000 nm) to stimulate mitochondrial function, which leads to increased ATP production, reduced oxidative stress (which leads to less inflammation), and better tissue regeneration.
There are no known side effects, though occasionally there are some mild short-term treatment reactions. It is cleared by FDA, Health Canada, Europe, and Australia for muscle and joint pain, and it is widely used in the US.
How does PBM work?
Primary effect (absorption)
There is a consensus that cytochrome c oxidase (CcO) in mitochondria is the primary photo-acceptor of PBM light, with a cascade of molecular events following such absorption. There are some additional mechanisms, but the CcO pathway explains most of the benefits seen from PBM.
Secondary effects (mitochondrial)
Following light absorption by CcO, there is increased oxygen consumption by mitochondria, with a corresponding increase in ATP production, a burst of reactive oxygen species (ROS) and nitric oxide (NO), followed by a reduction in ROS (i.e., superoxide, hydrogen peroxide).
Tertiary effect (intracellular)
The changes in ROS, reduced oxidative stress (and subsequent increase in ATP followed by more cAMP), resets NF-kb (reducing inflammation, cell death, and gene expression associated with degenerative diseases) and up-regulates gene transcription factor AP-1, which is associated with tissue repair, cell survival, increased activation of enzymes and secretion of growth factors and secondary messengers that signal to other cells.
Quaternary effects (extracellular)
The growth factors and secondary messengers serve as signal transduction messengers to neighboring cells, leading to indirect, distant, systemic responses in tissues/organs that have not absorbed photons via chemotactic, neural, lymphatic, and humoral effects.
PBM dosage is a combination of both light intensity and treatment time. If there is insufficient intensity or insufficient treatment time, there are no benefits. On the other hand, if there is too much intensity or too much treatment time, the benefits disappear. Typically, treatment time ranges from 20 seconds to 20 minutes, and the ideal intensity is in the range of 10 – 100 mW/cm2 for superficial pathologies less than 1 cm below the skin surface. There are exceptions and anomalies in the literature, however, that need some expert interpretation.
This cascade of events leads to improved speed and quality of tissue repair (skin, muscle, tendon, ligament, cartilage, bone, sensory nerves, motor nerves, and central nervous system), reduced inflammation and edema, improved function, and anti-aging effects.
Two papers I would like to highlight:
1. The effect of PBM on the duration and severity of postoperative pain: a double-blind trial
Moore KC, Hira N, Broome IJ, Cruikshank JA
Departments of Anaesthesia and General Surgery, The Royal Oldham Hospital, Oldham, UK; The Royal Hallamshire Hospital, Sheffield, UK; General Practitioner, Pennymeadow Clinic, Ashton-under-Lyne, UK
This trial was designed to test the hypothesis that LLLT reduces the extent and duration of postoperative pain. Twenty consecutive patients for elective cholecystectomy were randomly allocated for either LLLT or as controls. The trial was double blinded. Patients for LLLT received 6–8 minutes of treatment (GaAlAs: 830 nm: 60 mW CW: CM) to the wound area immediately following skin closure prior to emergence from general anesthesia (GA). All patients were prescribed on-demand postoperative analgesia (intramuscular [IM] or oral, depending on pain severity). Recordings of pain scores (0-10) and analgesic requirements were noted by an independent assessor. There was a significant difference in the number of doses of narcotic analgesic (IM) required between the two groups (controls n=5.5; LLLT n=2.5). No patient in the LLLT group required IM analgesia after 24 hours. Similarly, the requirement for oral analgesia was reduced in the LLLT group (controls n=9; LLLT n=4). Control patients assessed their overall pain as moderate to severe compared with mild to moderate in the LLLT group. The results justify further evaluation on a larger trial population.
2. Double blind crossover trial of low level laser therapy in the treatment of post herpetic neuralgia
Moore KC, Hira N, Parswanath K, Copparam J, Ohshiro T
Departments of Anaesthesia and General Surgery, The Royal Oldham Hospital, Oldham, UK
Postherpetic neuralgia can be an extremely painful condition that—in many cases—proves resistant to all the accepted forms of treatment. It is frequently most severe in the elderly and may persist for years with no predictable course. This trial was designed as a double-blinded assessment of the efficacy of LLLT in the relief of the pain of postherpetic neuralgia, with patients acting as their own controls. Admission to the trial was limited to patients with established postherpetic neuralgia of at least six months’ duration and who had shown little or no response to conventional methods of treatment. Measurements of pain intensity and distribution were noted over a period of eight treatments in two groups of patients each, of which received four consecutive laser treatments. The results demonstrated a significant reduction in the pain intensity and distribution following a course of PBM.
Many individuals who develop substance use disorders (SUD) are also diagnosed with mental disorders. Multiple national population surveys have found that about half of those who experience a mental illness during their lives will also experience a substance use disorder.
PBM has positive effects on the brain, including reduced depression and anxiety, improved cognitive function in healthy adults, and on various forms of dementia. In 2018, Cassano conducted a double-blind RCT on patients with major depressive disorder. He demonstrated an "anti-depressive effect with medium to large effect size and significant findings" . In 2016, Disner showed in an RCT that PBM enhanced the effects of attention bias modification treatment of depression . In 2009, Schiffer treated 10 patients with major depression, including 9 with anxiety, 7 with a past history of substance abuse (6 with OUD, and 1 with an alcohol abuse history), and 3 with post-traumatic stress disorder. These patients experienced highly significant reductions in both depression and anxiety scores following treatment, with the greatest reductions occurring at two weeks.
PBM addresses three components that are typically present in OUD:
- PBM reduces pain (diminishing the initial use of opioids).
- PBM is regenerative (helping heal the underlying cause of the pain).
- PBM decreases a psychological component of OUD (depression and anxiety).
It can be used exclusively or as an adjunct to existing treatments.
Given the evidence for its efficacy, we believe PBM should be part of the solution to the opioid crisis.
Founder and CEO
THOR Photomedicine Ltd
Disclosure: James Carroll is Founder & CEO of THOR Photomedicine Ltd, as well as Co-founder of and Investor in Lumithera, Inc.