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Trigger Point Ozone Injection Protocol
Concentration, volume per point, number of points and schedule for ozone trigger point (myofascial) injections, with Madrid's dose beside the doses studies used.
Quick answer: For ozone trigger point (myofascial) injections, Madrid lists 3–5 mL per point at 6–9 µg/mL. Studies used 1–8 points per session, weekly for 3 weeks in two trials and a single session in one trial. MediSkill limit: 20 mL per session.
Warning
Requires hands-on training from an experienced physician
Trigger point ozone injection should only be performed by a practitioner trained in it by an experienced physician.
Practitioner-only procedure. Injecting ozone into muscle is done by trained, licensed clinicians. This sheet is a reference for them. It is not a self-treatment guide and not medical advice. Strict sterile technique is required every time.
What are the basics of ozone trigger point injection?
- A trigger point is a tender knot in a muscle. In trigger point injection, ozone-oxygen gas goes into the muscle at the knot. Trials have used it for myofascial pain in the upper trapezius (neck and shoulder), fibromyalgia and widespread musculoskeletal pain.
- Madrid calls this microdosing. Trigger points sit deep in the muscle, so the injection is intramuscular. The volume is 3 to 5 mL depending on where the point is, at 6 to 9 µg/mL. Its Table 1B lists the levels as low 6, medium 7 and high 9 µg/mL.
- Madrid's Table 1B lists a much smaller volume for this microdosing row (0.1 to 0.3 mL) than its section 12 (3 to 5 mL for trigger points). Madrid does not explain the gap. This sheet uses section 12, because the trials used similar volumes.
- Madrid gives no number of points per session and no schedule for trigger points. The trials below fill that gap, and they also used higher concentrations than Madrid: 10 to 30 µg/mL. Both are shown, labeled by source. MediSkill limit: 20 mL of gas per session in total, whatever the number of points.
- The ISCO3 method sheet for microdoses (MET/00/18, which Madrid cites) is more generous: trigger points get 3 to 5 mL at 10 to 20 µg/mL per point, up to twice a week and no more than 8 points at once. It warns of local irritation above 9 µg/mL, and pain above 15 µg/mL.
- Madrid's dental section mentions a different dose for jaw muscles (masseter and others): trigger point injections of 2 mL at 10 to 20 µg/mL.
- Acupuncture points are a different procedure (intradermal, 0.1 to 0.3 mL a point). See the acupuncture point sheet.
Sources: Madrid Declaration on Ozone Therapy, 4th edition (ISCO3, 2025), sections 12 and 1.12 (Table 1B) and the TMD section; trials in the study list below. Paraphrased.
What dose and technique are used for ozone trigger point injection?
Madrid's microdosing dose is shown next to the doses the trials used. They are different, and the trials are small.
| Madrid | What the studies used | |
|---|---|---|
| Route | Intramuscular, at each trigger point. | Intramuscular into the most painful trigger point (two trials) or into 4 to 8 points with a fanning motion (one trial). |
| Concentration | 6, 7 or 9 µg/mL (the ISCO3 method sheet says 10 to 20). | 10 µg/mL (Korkmaz 2023), 12 µg/mL (Eldemrdash 2024), 15 µg/mL (Raeissadat 2018), 30 µg/mL (a retrospective fibromyalgia study, Research Square 2021 preprint). |
| Volume per point | 3 to 5 mL depending on the anatomical location. | 5 mL (Korkmaz, Eldemrdash), 8 mL (Raeissadat), 2 mL (fibromyalgia study), 3 mL (Vélez 2014, a fibromyalgia series that also used rectal ozone and IV ozonated saline, a co-treatment MediSkill does not advise). |
| Points per session | Not stated. | 1 point (Korkmaz, Raeissadat). 4 to 8 points of 5 mL each, so 20 to 40 mL in total (Eldemrdash). MediSkill limit: 20 mL per session. |
| Schedule | Not stated. ISCO3 method sheet: up to twice a week, no more than 8 points at once. | Weekly for 3 weeks (Korkmaz, Raeissadat). One session (Eldemrdash). Twice a week for 4 to 5 weeks in the two fibromyalgia studies. |
| Needle | Not stated. | 27G, 40 mm, inserted at 90 degrees with the patient seated (Korkmaz). 22G, inserted 1 to 2 cm from the point at 30 degrees, then fanned (Eldemrdash). 22G, 1.25 inch (Raeissadat). |
Madrid's base rule applies: start with a low dose and increase gradually (section 2). The higher trial concentrations are not Madrid dosing.
What are the best tips when using ozone trigger point injection?
- Locate the tender knot by touch first. Both single-point trials injected only the most painful point when a patient had more than one.
- Start at the low end of Madrid's range and raise the dose over sessions if needed, as Madrid's titration rule says.
- Inject slowly. Madrid says slow injection and distraction reduce the pain that ozone can cause.
- If you use a local anesthetic, place it above the ozone in the syringe path so it does not oxidize. Madrid says oxidized anesthetic feels like intense burning (section 4.2, written for paravertebral injection).
- The two single-point trials paired the injections with a home program of stretching, posture and relaxation exercises.
- Side effects in the trials were few. One trial reported a single transient flare of local pain, and the other two reported no adverse events.
What are the precautions for ozone trigger point injection, and who should avoid it?
- Never breathe ozone gas. Keep the room ventilated.
- Sterile technique every time. Madrid says most serious side effects trace back to malpractice, including technique, asepsis and antisepsis. Its reported serious events include septic arthritis of the knee after intra-articular infiltration and abscess after paravertebral injection. It also reports one death from sepsis after a paravertebral infiltration done without proper asepsis (Madrid Declaration on Ozone Therapy, 4th edition (ISCO3, 2025), section 2.5).
- Clean the skin with an antiseptic and let it dry before the needle goes through. Use sterile, single-use needles and syringes, and ozone-resistant syringes for the gas.
- Check with your licensing board that this procedure, and anything you inject along with the ozone, is within your scope of practice.
- Never inject ozone gas into a vein or an artery. Madrid strongly discourages both because of the risk of air embolism, and lists embolic events after paravertebral and intradiscal injections among its serious adverse events.
- Needle depth matters at the neck and upper back. Know the anatomy under the point before you inject, and use the shortest needle that reaches the muscle.
- Madrid lists embolic and neurological events after paravertebral injection among its serious adverse events. Trigger points next to the spine deserve the same care.
Contraindications
The Madrid Declaration lists these contraindications for systemic ozone:
- Direct inhalation of ozone gas. The fluid lining the lungs has no antioxidants to buffer it, so inhaled ozone is toxic.
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency (favism, acute hemolytic anemia). Madrid lists it as a contraindication and recommends testing, but whether it is absolute is debated. MediSkill protocols start low and go slow; see the contraindications article.
- Toxic hyperthyroidism (severe Graves' disease)
- Thrombocytopenia (platelets under 50,000) and severe coagulation disorders
- Severe cardiovascular instability
- Acute alcohol intoxication
- Recent acute myocardial infarction
- Acute massive hemorrhage
- Convulsive states
- Hemochromatosis
- Patients receiving intravenous copper or iron therapy
Pregnancy. Madrid advises avoiding ozone therapy in the first trimester (weeks 0 to 13) and reserves its use in pregnancy for specialists in gynecology and obstetrics.
More detail
Steps
- Find and mark the trigger point by touch. Pick the most painful one if there are several.
- Clean the skin with an antiseptic and let it dry.
- Draw up the ozone-oxygen gas at the chosen concentration in an ozone-resistant syringe.
- Insert the needle into the point. Studies used a 90 degree angle with a 27G, 40 mm needle, or 30 degrees entering 1 to 2 cm away from the point and fanning.
- Inject slowly while watching the patient.
- Remove the needle and apply light pressure. Repeat at other points only if your protocol uses more than one.
Equipment
- Ozone generator with an ozone-resistant gas path (quartz glass, titanium, silicone)
- Medical oxygen tank and regulator
- Ozone-resistant syringes (5 to 10 mL) and 22G to 27G needles
- Antiseptic and sterile supplies
What the studies used
Study doses are listed as printed in each paper and are not Madrid dosing.
- In a randomized trial of 62 people with upper trapezius myofascial pain, ozone and lidocaine injection both beat dry needling on pain, with no difference between ozone and lidocaine. Ozone was 8 mL at 15 µg/mL into the most painful point, weekly for 3 weeks (Raeissadat 2018).
- In 45 people with myofascial neck pain, 5 mL at 10 µg/mL weekly for 3 weeks eased pain, but lidocaine eased it more (interaction p=0.028). No adverse events were reported (Korkmaz 2023).
- In 45 people with chronic musculoskeletal pain, 5 mL at 12 µg/mL into each of 4 to 8 points in one session gave lower pain at 3 weeks than betamethasone alone (VAS, a 10-point pain score, 2.73 vs 4.27). No adverse events were reported (Eldemrdash 2024).
Evidence is thin and mixed: three small randomized trials, one of which favored the lidocaine comparison, and all using higher concentrations than Madrid lists for trigger points. Madrid gives no schedule. None of the trials showed ozone beating lidocaine.
Learn more
Background, benefits and research on injections: Ozone injections, full article. Related: Ozone therapy for pain and ozone therapy for fibromyalgia.
Related protocols: Acupuncture Point Ozone Injection Protocol, Subcutaneous Ozone Injection Protocol, PRP and Ozone Injection Protocol.
Other injection protocols
For licensed practitioners. Educational reference only, not medical advice. Follow your scope of practice and local regulations.