Problem Solving Part 1: Can You Have Too Much of a ‘Good Thing’?

Veterinary Laser/PBM therapy is still very much in the Frontier Medicine category, so it is imperative that we, the Veterinary profession, as The Animal Advocates, maintain authority over how and where this therapy is used.

Veterinarians, when taking on new technologies such as Laser therapy, must remain healthily wary about linearly extracting & extrapolating data re dosimetry and frequency etc. from Human Laser therapy, straight across onto our Veterinary patients.

It has now been over 4 decades since cats were treated by Vets as small dogs or shrunken hairy little people. It has been over 3 decades since we as Vets considered all canine breeds the same re physiology & biochemistry & pharmacology. Yet, out on the road during a recent trip calling into Veterinary clinics to demonstrate our particular Laser machine, I heard time and time again, of non-Vets giving human field Laser treatment advice to other Veterinary Laser users, without any thought or knowledge of the inter and intra-species variations of our Veterinary patients.

Even though our Vets1laser users per se are not having the issues reported below-in order to protect PBM therapy from getting bad press and to protect our veterinary patients from insufficient or excessive exposure, we have written the following set of open posts to help Veterinary Laser users problem-solve issues the way Veterinarians should and would do.

 Trouble Shooting Cogitations

Part 1: Increasing the Treatment Session  Frequency to 3-4 times a day?  No!

You can have too much of a ‘Good Thing’.

We prefer to pace out the therapy sessions due to species-specific idiosyncrasies and to give the body time to respond to the cascade and chemical responses triggered within it by each Laser therapy session However, we now note a recent trend to move to more frequent use, regardless of the species being treated, with recommendations to administer therapy every 6-8 hours in some presentations.

This is a cause for concern, akin to the incorrect belief, “Well if some works, then more must be better” and we all know that is not true.

PBM may not be a primary chemical or a pharmaceutical drug, but for many PBMT is regarded 1,2 as a ‘Drug-therapy Equivalent.’ PBMT may not elicit the same side effects as mainstream drug therapy but that does not mean we can abandon any concerns about potential, as yet unknown, side effects.

PBM modulates the ancient primordial1,2 photoacceptive properties of known powerful intra-body molecules to modulate metabolic and oxidative pathways and the cellular signalling responsible for the survival or death of a cell. What we don’t know is whether other photoacceptors are in that area., if they are also affected by light therapy-perhaps adversely especially if their threshold is exceeded wherein, we could inadvertently target prokaryotic or neoplastic cells.

Mitochondria are the main target of the therapy3. As both the major production and scavenging site of reactive oxygen species, mitochondria maintain a tight balance between the two, a balance that is critical for ROS-dependant signalling and for avoiding free-radical damage that leads to cell death3.

The site you first start treating is not the same site you come back to 6 or 12 hours later. Changes have occurred in that time, are occuring or need time to occur so when you come back to treat too early, then you either negate the benefits of the earlier session or could indeed be causing some toxicity in the cytosol.

On a microcellular in vitro level, we know for mesenchymal stem cells(MSC) a single NIR stimulation will produce the most prominent effects on mitochondrial membrane potential and ATP generation between 3-6/7hours post treatment4

In a study on Rat bone marrow MSCc exposed to a single NIR treatment, an increase in cell proliferation persisted for 48 hours.

A study on geniculate ganglion neuronal cells and the effect of PBM on apoptosis, the change in the ADP/ATP ratio took 3 days to become evident. (5)

Each laser session induces a reaction in the body: you need to give the body time to work on these, now intra-body, chemical/neuromodulation cascading events. The toxicity risk of any medicine is proportionate to the actual dose, both as a stand-alone dose and as a cumulative risk- and PBM/Laser therapy is no different.

Four species concerns come into play.

1)Birds have a high metabolism to start with. Adding in multiple PBMT sessions in a short period has to carry some risk of overstimulating the bird’s metabolism.

2) Cats are very vulnerable to stress in general, from oxidative stress to behavioural stress. Users of older model laser machines had concerns that daily use put the cat in an oxidative stress zone and so they recommended a 48-hour frequency.

With allodynia cases, a percentage end up having a bad day following the initial session but over 48 hours will begin to really benefit with dramatic drops in neuropathy. By that stage, you have a much less uncooperative patient than if you rushed the cat back in 24 hours later whilst it was still in the post-treatment storm. The rebound storm issue, though rare, appears to occur on the first treatment of a chronic case in subsequent sessions, hence why important to pace and space where you can. Behaviour Specialists talk of it taking a cat up to 72 hours to recover from the stress triggered by any Vet visit, so always good to space the timings.

3)Dogs. When acute ill or badly injured, dogs often go into a metabolic hold, whereby the body expresses a ‘low T3 syndrome’4 to act to limit protein loss by decreasing metabolic rate during chronic or severe illness. Ramping up the metabolism, even focally, by the application of multiple Laser sessions in 24 hours may not be in any patient’s best interest.

4)Humans. On a personal experience level-as someone who has had Class IV laser treatments themselves, not all treatment sessions evoke the same post-treatment response. Sometimes the effect is immediate and ergogenic. Less often, but it does occur, there is a need to curl up and sleep or there can be on occasions, depending on the lesion, unpleasant but not distressing symptoms of mild muscle cramping before muscle relaxation or literally feeling the perfusion resetting back to normal in a limb. Sometimes, one can feel mildly nauseous post-therapy for some hours. When those issues are occurring, or in the case of the veterinary patient with allodynia, the last thing one wants is anyone near them or requiring one to remain still and constrained even for another laser session These issues settle within 24 hours. By then, one is either happy to have another treatment session or be so recovered as not to need a session.

I imagine many veterinary patients would have similar experiences. In fact, some owners do report the pet being less mobile for the first few sessions. This is explained to the owner as an encouraging sign that suggests that increasing blood flow and reperfusion are occurring in that area. Whilst that is true, we also don’t want a reperfusion injury issue situation wherein we have overwhelmed the body’s resources to deal with a sudden demand for toxin removal by over-treating with too many sessions of PBMT.

With the newer suggestion of every 6–8-hour application not based on strong peer-reviewed studies, one has to ask if there is a dosage selection or technique or disease presentation variant contained within the proponent’s findings and hence their recommendations of multiple daily PBM sessions. If so, that recommendation-then truly based on unique operator technique or dosage – may not extrapolate to other users safely but rather as an increased risk of adverse response. Whilst the consideration of the Arndt-Schulz Law, and Hueppe’s Rule suggests it is unlikely to overdose-that doesn’t negate the risk of over-treatment, thus triggering the Law of Unintended Consequences.

 In my opinion, given the current state of knowledge, failing to wait 24hrs between treatments, in all but the most agonising of pain patients, could induce avoidable distress, increase the risk of adverse responses and over time induce habituation.

The existing treatment guidelines have stood the test of time and brought much respect to PBMT. If we intend to change what works, then there first has to be more in-depth evidence providing that the benefits outweigh the risks. Until then, our advice for session frequency still is as below.

Traditional Treatment Frequency

Improve by Four or do No More

A) INDUCTION.

Chronic :Every 48hrs x 6-12 treatments

Acute: Every 24hr-48hrs x 6-12 treatments

Post-op: 1-2 Sessions

(For some Dental extractions; wait for 24hrs post-op. Incisions/Dental scaling-Same day).

B.TRANSITION:

Gradual decrease to twice a week, then once a week 

C. MAINTENANCE.

Monthly-Seasonal as patient dictates.

REFERENCES

  1. Steering the multipotent mesenchymal cells towards an anti-inflammatory and osteogenic bias via Photobiomodulation therapy: How to kill two birds with one stone. Amaroli et al. 2022. Journal of Tissue Engineering; 13: 1–17 DOI: 10.1177/20417314221110192
  2. The nuts and bolts of low-level laser (light) therapy.Hoon Chung et al 2012 Ann Biomed Eng ; (2):516-33.doi: 10.1007/s10439-011-0454-7.    PMCID: PMC3288797 DOI: 10.1007/s10439-011-0454-7.
  3. Eroglu et al. Photobiomodulation has rejuvenating effects on aged bone marrow mesenchymal stem cells. Sci Rep 2021 Jun 22;11(1):13067. doi 10.1038/s41598-021-92584-3.
  4. Ferraresi C et al. Low-level laser (light) therapy increases mitochondrial membrane potential and ATP synthesis in C2C12 myotubes with a peak response at 3-6 h. Photochem Photobiol 2015 Mar-Apr;91(2):411-6. doi 10.1111/php.12397. Epub 2014 Dec 30.
  5. Ferguson DC. Thyroid hormones and antithyroid drugs. In: Riviere JE, Papich MG, editor. Veterinary pharmacology and therapeutics. 9th ed. Wiley Blackwell, Iowa, 2001;745

Reading Material;  

McMillan MW. Surgical Time-Out Procedures. 2023 JSAP:64:69-77

Kim H. et al. Medical lasers 07/2023. Effect of 850nm PBM on adenosine diphosphate/adenosine triphosphate measure of apoptosis in GGNC cells in vitro.

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