Effectiveness of Mitragynine Topical Patch for Pain Reduction in Myofascial Pain Syndrome

Официальное название

Effectiveness of Mitragynine Topical Patch From Kratom for Pain Reduction in Myofascial Pain Syndrome of Upper Trapezius Muscle: Double Blinded Placebo, Randomized Controlled Trial

Обзор

Myofascial Pain Syndrome (MPS) is one of the leading causes of both acute and chronic musculoskeletal pain encountered in clinical practice.¹ The most common presentation is low back pain, followed by pain in the neck and scapular regions.² These symptoms significantly affect quality of life and work performance. A common site involved in neck pain syndrome is the trapezius muscle, which may cause pain in the shoulder, neck, and occipital region. In some patients, neurological symptoms such as goosebumps or dizziness may also occur.³ Pain can occur in individuals of all age groups and may be either acute or chronic. It can arise from injuries or various diseases. Pain may result from different pathologies, including nociceptive pain, neuropathic pain, or a combination of both. Current medical treatment guidelines include both conventional medications and herbal extract-based therapies. In the 2022 National List of Essential Herbal Medicines of Thailand, several herbal formulations are indicated for pain relief. Oral preparations include Khasai Sen, Thorani Sandhakhat, and Ya Phasom Thao Wan Priang, while topical preparations include chili-based formulations, plai preparations, and plai oil. These remedies are indicated for the relief of body aches and muscle pain.⁶ Kratom, or \*Mitragyna speciosa\* (Korth.) Havil., is a plant belonging to the Rubiaceae family. In southern Thailand, it is commonly known as "Thom." Kratom leaves contain a variety of chemical constituents, including alkaloids, flavonoids, triterpenes, and phenolic compounds. Among these, indole alkaloids represent the major group. The principal active compound is mitragynine, which accounts for approximately two-thirds of the total alkaloid content, or about 66% by weight.⁷ Pharmacologically, orally administered mitragynine affects both the autonomic and central nervous systems. It possesses analgesic properties through binding to opioid receptors. Additionally, it reduces pain signal transmission to the brain via the noradrenergic and serotonergic systems.⁸ The mitragynine pain-relief patch used in this study is a product containing kratom extract formulated to deliver 10 milligrams of mitragynine per patch. It is designed as a topical patch, allowing the active ingredient to be absorbed into the outer layers of the skin without entering the bloodstream.¹¹ The patch consists of sodium alginate, pectin, and agar, which are naturally derived polymers commonly used as pharmaceutical excipients. The hypothesis of this study is that this locally acting "mitragynine pain-relief patch" can reduce pain and inflammation through the TRPV1 receptor mechanism described above. Neck, shoulder, and upper back pain are among the most common reasons patients attend general practice, orthopedic, and rehabilitation clinics. Patients with chronic myofascial pain syndrome (defined as pain persisting for more than three months) may be treated using various approaches depending on symptom severity, accessibility of services, and individual suitability. These approaches include oral medications, topical agents, local injections, acupuncture, physical therapy, and muscle stretching exercises. Many patients may have contraindications to oral medications, acupuncture, or regular attendance at physical therapy sessions, which can negatively affect their overall quality of life. Currently, topical medications are commonly prescribed for these patients at Hospital; however, treatment outcomes are often suboptimal. Moreover, most topical preparations produce a warming effect and may easily cause skin irritation, particularly in elderly patients with fragile skin. If the mitragynine pain-relief patch demonstrates effective pain reduction, it may be further developed as an alternative treatment option for these patients. The objective of this study is to evaluate the efficacy of a mitragynine-containing kratom pain-relief patch in patients with myofascial pain syndrome, compared with a placebo patch (a patch containing only the base formulation without kratom extract), and to determine whether there is a difference in pain-relief response between the two groups and, if so, how that difference manifests.

Подробное описание

1. Study Design Double-blinded, placebo-controlled randomized controlled trial 2. Study Setting Rehabilitation Clinic, hospital 3. Target Population Individuals with pain in the shoulder and neck region. 4. Study Population Patients with subacute myofascial pain syndrome involving the upper trapezius muscle. 5. Inclusion Criteria - Patients aged 18-50 years.

* Experiencing neck or shoulder pain for more than 3 months. * Diagnosed with myofascial pain syndrome, with the most tender trigger point located in the upper trapezius muscle and a pain score between 30-60 mm measured using the Visual Analogue Scale (VAS). 6. Exclusion Criteria - History of other neck-related conditions (e.g., whiplash injury, cervical radiculopathy, fibromyalgia syndrome, cervical spine surgery and/or fracture).

\- History of systemic diseases (e.g., rheumatism, multiple sclerosis, cervical myelopathy), hepatitis, liver failure, or kidney disease (serum creatinine \> 2.0 mg/dL).

\- Symptoms or conditions contraindicating the use of patches, such as wounds or infections at the painful site.

\- History of allergy to paracetamol or kratom. * History of allergy to adhesive patches/plasters. * Pregnant or breastfeeding women. * Receipt of treatment with analgesics other than paracetamol, physical therapy, dry needling/acupuncture, massage, or topical medications within the previous week. * Individuals who are unable to read or write. 7. Participant Withdrawal Criteria - Participants experiencing severe allergic reactions (e.g., anaphylaxis, severe rash, or intolerable itching).

* Receipt of treatments other than paracetamol or any interventions outside those specified in the study during the follow-up period. * Participants who wish to withdraw from the study. 8. Study Termination Criteria The study will be terminated if participants experience significant adverse events, including severe allergic reactions (anaphylaxis) or systemic side effects such as nausea and vomiting, in at least 7 participants, representing 10% of the sample size. 9. Sample Size 1. Irritation testing group: 10 healthy volunteers aged 18-50 years. 2. Efficacy testing group: 64 participants, calculated using the following formula: Sample size calculation for a randomized controlled trial with a continuous outcome μ\_trt = mean VAS change in the treatment group μ\_con = mean VAS change in the control group σ\_trt = SD in the treatment group σ\_con = SD in the control group λ = 1; α = 0.05; β = 0.2 The calculation was based on the study by Hsieh (2009) on the use of a diclofenac patch for reducing pain in the upper trapezius muscle.

Estimated values:

μ\_trt = 2.57; μ\_con = 3.92 σ\_trt = 1.75; σ\_con = 1.80 n\_trt = 28; n\_con = 28

Assuming a 10% dropout rate:

28 / 0.9 ≈ 32 participants per group Therefore, the total sample size ≈ 64 participants. 10 Variables and Operational Definitions Independent Variable

\- Pain intensity: Used to indicate the level of pain on a scale ranging from 0-100 mm.

Dependent Variable

\- Satisfaction score: Measured using a 5-point Likert scale with five levels of rating.

Confounding Variables

* Paracetamol consumption: Date and number of tablets taken will be recorded. * Neck muscle stretching exercises: Date and frequency of stretching exercises will be recorded.

Вмешательства

• Препарат mitragynine topical patch from kratom
  mirtagynine topical patch contains of 10 mg
• Препарат Placebo
  topical patch similar to active patch but no mirtagynine

Первичные конечные точки

• pain score [Срок оценки: 3 days after used]

Вторичные конечные точки (1)

• satisfaction score [Срок оценки: 3 days after used]

Критерии участия

Критерии включения

• \- Patients aged 18-50 years.
• Experiencing neck or shoulder pain for more than 3 months.
• Diagnosed with myofascial pain syndrome, with the most tender trigger point located in the upper trapezius muscle and a pain score between 30-60 mm measured using the Visual Analogue Scale (VAS).

Критерии исключения

• \- History of other neck-related conditions (e.g., whiplash injury, cervical radiculopathy, fibromyalgia syndrome, cervical spine surgery and/or fracture).
• History of systemic diseases (e.g., rheumatism, multiple sclerosis, cervical myelopathy), hepatitis, liver failure, or kidney disease (serum creatinine > 2.0 mg/dL).
• Symptoms or conditions contraindicating the use of patches, such as wounds or infections at the painful site.
• History of allergy to paracetamol or kratom.
• History of allergy to adhesive patches/plasters.
• Pregnant or breastfeeding women.
• Receipt of treatment with analgesics other than paracetamol, physical therapy, dry needling/acupuncture, massage, or topical medications within the previous week.
• Individuals who are unable to read or write.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

Таиланд · 1 центр

• Prince of Songkla university — Songkhla

Публикации

• Kruegel AC, Gassaway MM, Kapoor A, Varadi A, Majumdar S, Filizola M, Javitch JA, Sames D. Synthetic and Receptor Signaling Explorations of the Mitragyna Alkaloids: Mitragynine as an Atypical Molecular Framework for Opioid Receptor Modulators. J Am Chem Soc. 2016 Jun 1;138(21):6754-64. doi: 10.1021/jacs.6b00360. Epub 2016 May 18. PMID 27192616
• Goodwin B, Mitchell J, Major E, Podwojniak A, Brancaccio H, Rusinak K, King M, Tahir H. The efficacy of topical 8% capsaicin patches for the treatment of postsurgical neuropathic pain: a systematic review. Pain Manag. 2024 Oct-Nov;14(10-11):591-598. doi: 10.1080/17581869.2024.2433931. Epub 2024 Nov 26. PMID 39589498
• Hsieh LF, Hong CZ, Chern SH, Chen CC. Efficacy and side effects of diclofenac patch in treatment of patients with myofascial pain syndrome of the upper trapezius. J Pain Symptom Manage. 2010 Jan;39(1):116-25. doi: 10.1016/j.jpainsymman.2009.05.016. Epub 2009 Oct 12. PMID 19822404
• Takayama H. Chemistry and pharmacology of analgesic indole alkaloids from the rubiaceous plant, Mitragyna speciosa. Chem Pharm Bull (Tokyo). 2004 Aug;52(8):916-28. doi: 10.1248/cpb.52.916. PMID 15304982
• Cerezo-Tellez E, Torres-Lacomba M, Mayoral-Del Moral O, Sanchez-Sanchez B, Dommerholt J, Gutierrez-Ortega C. Prevalence of Myofascial Pain Syndrome in Chronic Non-Specific Neck Pain: A Population-Based Cross-Sectional Descriptive Study. Pain Med. 2016 Dec;17(12):2369-2377. doi: 10.1093/pm/pnw114. Epub 2016 Jun 20. PMID 28025371
• Borg-Stein J, Simons DG. Focused review: myofascial pain. Arch Phys Med Rehabil. 2002 Mar;83(3 Suppl 1):S40-7, S48-9. doi: 10.1053/apmr.2002.32155. PMID 11973695

Идентификаторы

NCT: NCT07713771 · REC.68-226-41-1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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