Photobiomodulation (PBMT): Therapy for Pain Management – A New Paradigm

Dr. Roberta Chow Quantum Pain Management – Sydney, Australia August 9, 2017

1 Roberta Chow, Disclosures

• I have no disclosures to report.

The contents of this activity may include discussion of off label or investigative drug uses. The faculty is aware that is their responsibility to disclose this information.

2 Planning Committee, Disclosures

AAAP aims to provide educational information that is balanced, independent, objective and free of bias and based on evidence. In order to resolve any identified Conflicts of Interest, disclosure information from all planners, faculty and anyone in the position to control content is provided during the planning process to ensure resolution of any identified conflicts. This disclosure information is listed below:

The following developers and planning committee members have reported that they have no commercial relationships relevant to the content of this webinar to disclose: AAAP CME/CPD Committee Members Dean Krahn, MD, Kevin Sevarino, MD, PhD, Tim Fong, MD, Tom Kosten, MD, Joji Suzuki, MD; and AAAP Staff Kathryn Cates-Wessel, Miriam Giles, Carol Johnson, and Justina Pereira.

All faculty have been advised that any recommendations involving clinical must be based on evidence that is accepted within the profession of medicine as adequate justification for their indications and contraindications in the care of patients. All scientific research referred to, reported, or used in the presentation must conform to the generally accepted standards of experimental design, data collection, and analysis. The content of this CME activity has been reviewed and the committee determined the presentation is balanced, independent, and free of any commercial bias. Speakers must inform the learners if their presentation will include discussion of unlabeled/investigational use of commercial products.

3 Target Audience

• The overarching goal of PCSS-O is to offer evidence-based trainings on the safe and effective prescribing of opioid medications in the treatment of pain and/or opioid addiction.

• Our focus is to reach providers and/or providers-in-training from diverse healthcare professions including physicians, nurses, dentists, physician assistants, pharmacists, and program administrators.

4 Educational Objectives

• At the conclusion of this activity participants should be able to: . Describe the most important characteristics of as medicine . Summarize the effect of light in the somatosensory nervous system most relevant to pain relief . Describe the broad range of tissue effects initiated by light which modulate pain . Evaluate the experimental and clinical evidence base for application in clinical practice . Identify patients most likely to respond to PBMT

5 Photobiomodulation Therapy (PBMT) – MESH definition NLM

“A form of light therapy that utilizes non-ionizing forms of light sources, including , LEDS and BROAD- BAND LIGHT in the visible and spectrum.

It is a non-thermal process involving endogenous chromophores eliciting photophysical (i.e. linear and non-linear) and photochemical events at various biological scales.

This process results in beneficial therapeutic outcomes including but not limited to the alleviation of pain or inflammation, immunomodulation and promotion of wound healing and tissue regeneration.”

6 Synonyms

• Low level laser therapy • Photobiostimulation • Low reactive-level laser therapy • Biomodulation • Low intensity laser therapy • Biostimulation • Low level light therapy • Cold laser • Low energy laser irradiation • Soft laser • Low power laser • Laser therapy

It is called “LOW” because of the comparison with surgical “HIGH” power lasers, but it does not really describe the true nature of the lasers.

7 Case Study

• Major SO 39 year Female Afghan Veteran . Nurse 17 years in military (special ops) . Severe widespread pain 24/7 for 1 yr − Hypermobile − Knee pain +++ (bilat tib osteotomy), − L5/S1 back injury − Thoracic pain - myofascial − Rt ulnar nerve neuropathy − etc. . PTSD (2009)

8 Treatment at presentation (09/2016)

Non-drug Drug Therapies

• Exercise physiology • Buprenorphine sublingual tabs (exercises made knee pain • Morphine sulphate Pregabalin worse) 150mg bd • Chiropractic – helped with mobility • Venlafaxine 225mg daily • Pain psychologist • Quetiapine 75mg at night • Pain specialist • Ketamine infusions • Pain physiotherapist • Naprosyn 500mg daily (PRN) • Psychiatrist • Celecoxib 200mg daily • Diazepam 5-10mg prn …..in hospital at the time she came to me (unable to cope at Despite all these therapies she home) was not getting any better

9 PBMT

Where do we start with a patient like this?

• Establish a “hierachy” of the pain problems …. ….what is the most troublesome area? • Look for nociceptive pain generators in the areas of pain – such as painful entheses or trigger points • Is there a neuropathic component? • Explain the “hardware” vs software nature of pain.. . diagnostic imaging findings do not necessarily reflect clinical “pain” experiences . PBMT treats “software” – nerves, muscles, tendons etc. which cannot easily be imaged – “reprogramming software” • Importantly – she wanted to get better

10 Light Based Therapies

• Greeks and Egyptians worshipped light • Neils Finsen - Nobel Prize 1903 • Blue light for neonatal jaundice • Red light for blindness of prematurity • Light for depression (SAD) • Vitamin D is synthesized in the skin by UV light • UV for psoriasis

Nobel Prize Medicine 1903

Synthesis of Vit D in skin

11 Clinical Application of Photobiomodulation Therapy

12 Principles of Treatment

• Apply the laser/light to tender areas in the region of clinical interest • Treat the lymphatics pertaining to the area • Treat associated tender points in the associated dermatomes and/or myotomes • Treat the spine overlying the nerve roots • +/- treat the tibia or sternum for stem cell stimulation • +/- treat “brain”

13 Q: What is the “medicine”? – A:

A is:

• a discrete bundle (or quantum) of electro- magnetic (or light) energy.

• always in motion at the constant speed of light

• can have particle-like interactions (i.e. collisions) with and other particles

• both a wave and a particle all the time

14

Einstein

1916

Light Amplification by Stimulated Emission of Radiation

15 Laser Characteristics

• Monochromatic i.e. single wavelength • Coherence . the basis of speckle formation) • Lack of divergence (original lasers) . diode lasers do have divergent beams

16 Laser Therapy - Tunér and Hode 2002 Laser Parameters

• Wavelength (nm) from 400 to 1064 nm (red 650, 670 nm and infrared 810, 904 nm most commonly used) • Power (W or mW) 1 mW to 500 mW • Mode (pulsed or continuous) • Time applied (seconds to minutes) • Site applied (anatomical location) • Area (localised or scanning)

From these we can calculate the dose of light delivered – in Joules 17 Primary effects of light in cells

The First Law of Photochemistry states that “for light to exert an effect it must be absorbed” …and something must absorb it

Smith KC. The Photobiological Basis of Low Level Laser 18 Radiation Therapy. Laser Therapy. 1991; 3(1): 19-24. How does it work?

Chromophores are molecules which are “light absorbers” in membranes and the respiratory chain, which absorb photons

After absorption electromagnetic energy is transduced to electrophysical and/or electrochemical energy. Not heat!!

 Cytochrome C oxidase*

 Porphyrins and Flavins

 Adenine Nucleotides (NADH)

19 Cytochrome C oxidase in Mitochondrial Membrane

• ATP synthesis/inhibition • Induction of NF-κB • Gene transcription • Expression of growth factors • bFGF, VEGF, TGF • Increased inducible nitric oxide synthase • Production of reactive oxygen species

20 Secondary cellular effects of light absorption

• Reduces action potentials in nerves

• Reduces inflammation

• Reduces muscle spasm

• Reduces swelling/oedema

• Stimulates tissue repair/wound healing

• Modulates CNS neurotransmitter production

• Initiates systemic effects (abscopal effect)

21 Laser effects in the somato- sensory nervous system HUMAN STUDIES ANIMAL STUDIES 18 human studies 25 animal studies

Established the Established the principle principle that laser that transcutaneous selectively suppresses laser can inhibit action nociceptor (A and C potentials(block nerve fibre) action potentials conduction) in underlying nerves Has specific anti- inflammatory activities

Chow R, Armati P, Laakso EL, Bjordal JM, Baxter GD. Inhibitory effects of laser irradiation on peripheral mammalian nerves and relevance to analgesic effects: a systematic review. Photomed 22 Laser Surg. 2011; 29 (6): 365-81. Studies showing inhibition of neural stimuli

following noxious stimuli

Tsuchiya D, Kawatani M, Takeshige C. Laser irradiation abates neuronal responses to nociceptive stimulation of rat-paw skin. Brain Res Bull. 1994; 34(4): 369-74. ……………………….. Kasai S, Kono T, Sakamoto T, Mito M. Effects of low-power laser irradiation on multiple unit discharges induced by noxious stimuli in the anesthetized rabbit. J Clin Laser Med Surg. 1994; 12(4): 221-4.

23 Neural blockade by direct application of light to nerve following pro-inflammatory stimulus

Sato T, Kawatani M, Takeshige C, Matsumoto I . Ga-Al-As laser irradiation inhibits neuronal activity associated with inflammation.

Acupunct Electrother Res 1994 Jun-Sep 19(2-3) 141-51

24 Microtuble Polymerisation and Transport Function

Microtubule Associated Proteins (MAPS) are ATPases Images of microtubule arrays (Alberts - Molecular of the Cell 4th edition)

25 Transport within the nerve is temporarily disrupted by disruption of the cytoskeleton

Chow R, David M, Armati P. 830-nm laser irradiation induces varicosity formation, reduces mitochondrial membrane potential and blocks fast axonal flow in small and medium diameter rat dorsal root ganglion neurons: implications for the analgesic effects of 830-nm laser’. J 26 Peripher Nerv Syst. 2007; 12(1): 28-39. Laser Causes Neural Blockade

• Depletes decreases mitochondrial membrane potential • Decreases ATP • Disrupts polymerisation of microtubules • Disrupts function of ATPases e.g. Na+K+ATPase • Disrupts fast axonal flow - organelles and mitochondria • Affects small diameter, A and C fibre, nociceptors. • Occurs within 5-10 mins in vitro and 10- 20 mins in vivo A C fibre (nociceptors) lie • Is reversible superficially in skin

• Represents neural blockade (Peripheral Neuropathy Vol 1 2005 Eds • Blocks transmission of noxious impulses Dyck & Thomas)

27 Cascade of Neural Blockade

Laser blocks Reduces anxiety conduction in Reduces pain Improves mobility nociceptors Reduces drug intake

Reduces nerve Reduces local Reduces excitability axon reflex oedema

Suppresses Suppresses neurogenic peripheral inflammation sensitisation Neuroplasticity Down regulates Reduces progression Reduces afferent input to second from acute to chronic input to the order neurons pain dorsal horn 28 Anti-inflammatory Effects

Pathways for acute pain relief by red or infrared LI

Local LLLT effects after first irradiation, Anti-inflammatory enhanced effect by repeated irradiation effects found in 21/24 laboratory Effects on biochemical inflammatory markers studies Number of controlled laboratory trials verifying results

Reduced PGE2 Reduced TNF Reduced IL1β Reduced COX-2 Reduced plasminogen levels (5) α levels (2) levels (3) mRNA levels (2) activator levels (1)

Effects on cells and soft tissue Bjordal et al. 2006, Photomed Laser Surg

Reduced Reduced Reduced Enhanced local oedema hemorrhagic neutrophil cell influx microcirculation (4) formation (7) formation (5) (4)

29 Anti-inflammatory effects demonstrated in human Achilles microdialysis study

30 Anti-inflammatory effects demonstrated in human Achilles microdialysis study

In this study subjects with Achilles Tendinopathy were asked to jump on the affected leg, activating the tendinitis. Microdialysis was performed before and after the activation with and without laser therapy.

Results: PGE2 levels were reduced in the laser group versus the control group

Conclusion: This study demonstrated a direct inhibitory effect of laser on local tissues to decrease response to pro-inflammatory stimuli.

31 Anti-inflammatory Effects

The anti-inflammatory effects of laser and anti-inflammatory drugs in animal studies are very similar

Laser therapy in rat paw edema

1,4

1,2

1

0,8

r Kontroll (Carrageenan)

e

t

i

l

i

l 0,6 l Laser 7.5 J/cm2

i

m NSAID (diclofenac) 0,4

0,2

0 0 1 2 3 4 -0,2 Timer Aimbire F, Lopes-Martins R, Albertini R, Pacheco M, Castro-Faria-Neto H, Martins P, et al. Effect of low-level laser therapy on haemorrhagic lesions Albertini R, Aimbire F, Correa FI, Ribeirob W, Cogob JC, induced by immune complex in rat lungs. Antunesc E, et al. Effects of different protocol doses of Photomedicine and Laser . 2007; 25(2): low power gallium–aluminum–arsenate (Ga–Al–As) laser 112-7. Laser (650nm) dose 7.5 Joules radiation (650 nm) on carrageenan induced rat paw oedema. Journal of Photochemistry and Photobiology B: 32 Biology 2004; 27(2-3): 101-7. mRNA gene expression of COX-2 vs reduction

in PGE2

Figure 2. mRNA gene expression of COX-2. Figure 3. PGE2 derived from COX-2 2 h after tendinitis The samples were collected 2 h after the induction. The values are represented by mean, error collagenase-induced tendinitis. *p < 0.05 and bars are SDs. **p < 0.01 versus control; **p < 0.01 versus control, #p < 0.05 ##p < 0.01 versus collagenase group. and ##p < 0.01 versus collagenase group.

Marcos et al 2011 LLLT in collagenase-induced Achilles Tendinitis in rats: Analysis of biochemical and biomechanical aspects. 33 J Orth Res Dec 2012 1945-1951 Muscle Effects

Laser (at the right dose) has direct effects on muscle to cause relaxation and change in algometry pressure within 10 to 15 minutes

Airaksinen O, Rantanen P, Pertti K, Pontinen P. Effects of the infrared laser therapy at treated and non-treated trigger points. Acupuncture & 34 Electro-therapeutics Research International Journal. 1989; 14: 9-14. Effects of 635 NM LLLT On Exercise Induced Skeletal Muscle Fatigue

Photomed & Laser Surgery Vol 26, 5, 2008 p 419-424 35 Effect of 830 NM LLLT On Muscle Recovery Applied Pre-Exercise

Lasers Med Sci (2009) 24: 857-863 Leal Junior et al

36 Tissue Repair

• Burns • Pressure sores • Traumatic wounds • Post-op wounds • Leg ulcers • Any conditions in which there is swelling, inflammation and pain.

37 Examples of Effects of Phototherapy on Immune Cells

Changes have been reported in:

• Neutrophils • Monocytes • Macrophages • Lymphocytes • Mast cells • e.g. • LLLT (830 nm, continuous, 150 mW/cm2) decreases reactive oxygen species (ROS) production by human neutrophils, modulating inflammation. Effect greater in smokers, who heal slowly and produce more ROS, than in non-smokers.

38 Fujikami Y et al J Clin Laser Med Surg 21(4):165-170 2003. Macrophages

LLLT

• (a) increases soluble protein mediators production by macrophages directly which • (b) increases fibroblast proliferation indirectly

Effective Ineffective 660, 820, 870 nm 880 nm

39 Young SR, Bolton P & Dyson M (1989) Lasers Surg Med 9:497-505 Lymphatic System Effects

40 0.88 J/cm2 628-nm HS27 human fibroblasts 74 genes up > 2-fold 37 genes down > 0.5 fold

J Invest Dermatol. 2003 May;120(5):849-57. Zhang Y, Song S, Fong CC, 41 Tsang CH, Yang Z, Yang M. Laser and mechanotransduction in collagen...... Laser makes tendons stronger

Neves et al 2011 Different power settings of LLLT on the repair of the calcaneal tendon. Photomed Laser Surg 29 (10) 663-668

42 What painful conditions can be treated?

• OA • Pudendal Neuralgia • RA • Shingles • Myofascial pain • Post-herpetic neuralgia • Tendnopathies • TMD • Back pain • Migraines and • Neck pain cervicogenic • Sciatica headache • wound healing

43 WALT Guidelines

44 So how did we treat Major SO?

• PBMT Prone – 15 mins Total Rx time – 30 mins Supine – 5 mins . Start treatment twice a week TLC = a large 904nm . Selected the primary area to cluster super treat at each visit – up to LED probe pulsed two areas – red and laser infrared . 20-30 mins treatment (nurse or physio* or doctor) . Aim is to reduce pain, relieve muscle spasm, treat trigger points, improve inflammation, reduce Large swelling and stimulate tissue scanning repair laser to left knee

45 Further Treatment

• Stopped exercise physiology • Continued physiotherapy Rx 1/week– mobilisation, strapping, exercise, manipulative techniques – 1 physio • Continued 1x/week Rx PBMT • Was able to leave hospital after 1 month and live at home (with two flights of stairs)

• Meds: by Jan 2017 • Ceased oral morphine • Reduced Buphrenorphine 0.2mg – 0.2mg – 0.2mg • Ceased celecoxib took PRN naproxen • Reduced pregabalin to 75 mg bid • No diazepam

46 Further Developments

• Experienced exacerbations at times when under stress – had to increase medication at times • Had several trigger point injections to glut medius at times • March 2017 – medically discharged from the army • Continued treatment – • Started photography as a business • June 2017 went to Paris for 3 months (arranged physio and laser therapy while away)

47 Summary of Effects

• In complex and chronic patients laser therapy laser therapy can be used as an adjunctive treatment to:

• Reduce pain - Neural blockade leading to reduction in central sensitisation; Anti-inflammatory effects especially at sites of enthesitis and in joints (knees); Reduce trigger point activity to facilitate more effective exercise; Improve lymphatic flow to promote healing and reduce interstitial oedema associated with chronic inflammation; Stimulate tissue repair to improve tissue healing at injured sites and strengthen ligaments and tendons with gradual reduction in medication.

These changes take time – months (to years)

48 Rewiring a brain with light

Chapter 4

Rewiring a Brain with Light

Using Light to Reawaken Dormant Neural Circuits

It is the unqualified result of all my experience with the sick that second only to their need of fresh air is their need of light; that, after a close room, what hurts them most is a dark room, and it is not only light but direct sun-light that they want.....People think the the effect is upon the spirits only. This is by no means the case. The sun is not only a painter but a sculptor.

49 Florence Nightingale, Notes on Nursing, 1860 Transcranial Low Level Laser (Light) Therapy for Traumatic Brain Injury

50 Laser Therapy for Neck Pain

51 Over 300 (RCT) clinical trials Over 3000 laboratory studies Over 30 new research papers a month

52 National Health and Medical Research Council (Australia)

Science to Art Prize 2013 Effects of laser on nerves

Thank you

53 References

1. Smith KC. The Photobiological Basis of Low Level Laser Radiation Therapy. Laser Therapy. 1991; 3(1): 19-24. 2. Chow R, Armati P, Laakso EL, Bjordal JM, Baxter GD. Inhibitory effects of laser irradiation on peripheral mammalian nerves and relevance to analgesic effects: a systematic review. Photomed Laser Surg. 2011; 29(6): 365-81. 3. Tsuchiya D, Kawatani M, Takeshige C. Laser irradiation abates neuronal responses to nociceptive stimulation of rat-paw skin. Brain Res Bull. 1994; 34(4): 369-74. 4. Kasai S, Kono T, Sakamoto T, Mito M. Effects of low-power laser irradiation on multiple unit discharges induced by noxious stimuli in the anesthetized rabbit. J Clin Laser Med Surg. 1994; 12(4): 221-4. 5. Chow RT, Johnson MI, Lopes-Martins RA, Bjordal JM. Efficacy of low-level laser therapy in the management of neck pain: a systematic review and meta-analysis of randomised placebo or active- treatment controlled trials. Lancet. 2009; 374(9705): 1897-908. 6. Sato T, Kawatani M, Takeshige C, Matsumoto I. Ga-Al-As laser irradiation inhibits neuronal activity associated with inflammation. Acupunct Electrother Res. 1994; 19(2-3): 141-51. 7. Wakabayashi H, Hamba M, Matsumoto K, Tachibana H. Effect of irradiation by semiconductor laser on responses evoked in trigeminal caudal neurons by tooth pulp stimulation. Laser Surg Med. 1993; 13(6): 605-10.

54 References (continued)

8. Bjordal JM, Lopes-Martins RAB, Iversen VV. A randomised, placebo controlled trial of low-level laser therapy for activated Achilles tendinitis with microdialysis measurement of peritendinous

prostaglandin E2 concentrations. Brit J Sport Med. 2006; 40: 76-80. 9. Marcos RL, Leal-Junior EC, Arnold G, Magnenet V, Rahouadj R, Wang X, et al. Low-level laser therapy in collagenase-induced Achilles tendinitis in rats: analyses of biochemical and biomechanical aspects. Journal of orthopaedic research : official publication of the Orthopaedic Research Society. 2012; 30(12): 1945-51. 10. Leal Junior EC, Lopes-Martins RA, Baroni BM, De Marchi T, Taufer D, Manfro DS, et al. Effect of 830 nm low-level laser therapy applied before high-intensity exercises on skeletal muscle recovery in athletes. Lasers Med Sci. 2009; 24(6): 857-63. 11. Baxter GC, Walsh DM, Allen JM, Lowe AS, Bell AJ. Effects of low intensity infrared laser irradiation upon conduction in the human median nerve in vivo. Exp Physiol. 1994; 79: 227-34. 12. Chow R, David M, Armati P. 830-nm laser irradiation induces varicosity formation, reduces mitochondrial membrane potential and blocks fast axonal flow in small and medium diameter rat dorsal root ganglion neurons: implications for the analgesic effects of 830-nm laser’. J Peripher Nerv Syst. 2007; 12(1): 28-39. 13. Kennedy W, Wendelschafter-Crabb G, Polydefikis M, McArthur J. Ch 34 Pathology and quantitation of cutaneous innervation. In: Dyck P, Thomas P, editors. Peripheral Neuropathy. 4 ed. Philadelphia: W.B Saunders; 2005. p. 873.

55 References (continued)

14. Albertini R, Aimbire F, Correa FI, Ribeirob W, Cogob JC, Antunesc E, et al. Effects of different protocol doses of low power gallium–aluminum–arsenate (Ga–Al–As) laser radiation (650 nm) on carrageenan induced rat paw oedema. Journal of Photochemistry and Photobiology B: Biology 2004; 27(2-3): 101-7. 15. Aimbire F, Lopes-Martins R, Albertini R, Pacheco M, Castro-Faria-Neto H, Martins P, et al. Effect of low-level laser therapy on haemorrhagic lesions induced by immune complex in rat lungs. Photomedicine and Laser Surgery. 2007; 25(2): 112-7. 16. Marcos RL, Leal Junior EC, Messias Fde M, de Carvalho MH, Pallotta RC, Frigo L, et al. Infrared (810 nm) low-level laser therapy in rat achilles tendinitis: a consistent alternative to drugs. Photochem Photobiol. 2011; 87(6): 1447-52. 17. Airaksinen O, Rantanen P, Pertti K, Pontinen P. Effects of the infrared laser therapy at treated and non-treated trigger points. Acupuncture & Electro-therapeutics Research International Journal. 1989; 14: 9-14. 18. Leal Junior EC, Lopes-Martins RA, Dalan F, Ferrari M, Sbabo FM, Generosi RA, et al. Effect of 655-nm low-level laser therapy on exercise-induced skeletal muscle fatigue in humans. Photomed Laser Surg. 2008; 26(5): 419-24. 19. Leal Junior EC, Lopes-Martins RA, Vanin AA, Baroni BM, Grosselli D, De Marchi T, et al. Effect of 830 nm low-level laser therapy in exercise-induced skeletal muscle fatigue in humans. Lasers Med Sci. 2009; 24(3): 425-31.

56 References (continued)

20. Fujimaki Y, Shimoyama T, Liu Q, Umeda T, Nakaji S, Sugawara K. Low-level laser irradiation attenuates production of reactive oxygen species by human neutrophils. J Clin Laser Med Surg. 2003; 21(3): 165-70. 21. Young S, Bolton P, Dyson M, Harvey W, Diamantopoulos C. Macrophage Responsiveness to Light Therapy. Lasers in Surgery & Medicine. 1989; 9: 497-505. 22. Zhang Y, Song S, Fong CC, Tsang CH, Yang Z, Yang M. cDNA microarray analysis of gene expression profiles in human fibroblast cells irradiated with red light. The Journal of investigative . 2003; 120(5): 849-57. 23. World Association of Laser Therapy (WALT). Laser dosage table for musculoskeletal disorders using 904 nm laser. 2010. 24. Johnstone DM, Coleman K, Moro C, Torres N, Eells J, Baker GE, et al. The potential of light therapy in Parkinson's Disease. ChronoPhysiology and Therapy. 2014; 4: 1-14. 25. Huang YY, Gupta A, Vecchio D, de Arce VJ, Huang SF, Xuan W, et al. Transcranial low level laser (light) therapy for traumatic brain injury. Journal of biophotonics. 2012; 5(11-12): 827-37.

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58

PCSS-O is a collaborative effort led by American Academy of Addiction Psychiatry (AAAP) in partnership with: Addiction Technology Transfer Center (ATTC), American Academy of Neurology (AAN), American Academy of Pain Medicine (AAPM), American Academy of Pediatrics (AAP), American College of Physicians (ACP), American Dental Association (ADA), American Medical Association (AMA), American Osteopathic Academy of Addiction Medicine (AOAAM), American Psychiatric Association (APA), American Society for Pain Management Nursing (ASPMN), International Nurses Society on Addictions (IntNSA), and Southeast Consortium for Substance Abuse Training (SECSAT).

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