Scientific Evidence — Axomera®

Galvanin: an electric-field sensor.

Cell with Galvanin-GFP in a DC electric field (cell culture). Galvanin relocates to the anode-facing side, where the rear forms; the leading edge points towards the cathode.

• Belliveau et al. identify Galvanin (TMEM154) as an electric-field sensor involved in directed cell migration.
• The fluorescent signal makes the protein's redistribution visible as the cell aligns with the field.
• The complementary Zhao footage shows how a cell's leading edge responds to a change in field direction.

What does this mean for Axomera?

Electric fields are a biological directional signal. Axomera creates a local electric field at the needle tip. These findings provide a basis for investigating how cells respond to this stimulus.

Acidity and pain: the electrochemical perspective

Acidic conditions can excite pain fibres. Cathodic electrochemistry can generate hydroxide, which can buffer acid. Alongside directed cell migration, this provides a second perspective on local electrical stimulation: its chemical environment.

A laboratory observation — not evidence of a treatment effect in patients. The videos show cell-culture experiments, not clinical Axomera treatment. Whether Galvanin and these signalling pathways mediate effects in treated human tissue remains a hypothesis. Galvanin and PI3Kγ/PTEN were investigated in separate studies; a direct signalling link is not established. Migration direction depends on cell type and experimental conditions; not all cells converge on a needle. The Zhao footage shows a neutrophil-like HL-60 cell, not a fibroblast. Neither video demonstrates pH normalisation, inhibition of inflammation or tissue regeneration in patients. The acidity references concern rat-skin laboratory preparations (Steen 1992; Reeh & Steen 1996). Buffering by Axomera is a model calculation, not measured normalisation of tissue pH in patients.

Video S3: Belliveau NM et al. Galvanin (TMEM154) is an electric-field sensor for directed cell migration. Cell 2026. Supplied as a format-converted copy without sound; embedded via Vimeo. No scientific annotations or recolouring added. Belliveau et al., Cell 2026 · CC BY 4.0 · Vimeo

Additional laboratory example: PI3K/PTEN

Neutrophil-like HL-60 cell, not a fibroblast. PHAkt-GFP marks the PI3K signal at the leading edge. After field reversal the cell turns towards the cathode. Zhao et al., Nature 2006, Supplementary Movie 5.

The receiver · Direction & field sensing

How cells sense electric fields and align their movement with them.

25. Core publication Belliveau et al. "Galvanin (TMEM154) is an electric-field sensor for directed cell migration." Cell. 2026. Open Access · CC BY 4.0 DOI

    Core publication on electric-field sensing: identifies Galvanin (TMEM154) as a sensor for directed cell migration. A molecular mechanism of galvanotaxis, not clinical proof of Axomera efficacy.

1. McCaig CD, Rajnicek AM, Song B, Zhao M. "Controlling cell behavior electrically: current views and future potential." Physiol. Rev. 2005;85(3):943-978. DOI
2. Zhao M, Song B, Pu J, et al. "Electrical signals control wound healing through PI3Kγ and PTEN." Nature. 2006;442(7101):457-460. DOI
3. Song B, Zhao M, Forrester JV, McCaig CD. "Electrical cues regulate orientation and frequency of cell division and wound healing in vivo." PNAS. 2002;99(21):13577-82. DOI
4. Hoare JI, Rajnicek AM, McCaig CD, Barker RN, Wilson HM. "Electric fields are novel determinants of human macrophage functions." J. Leukoc. Biol. 2016;99(6):1-11. DOI
5. Zhao Z, Watt C, Karystinou A, et al. "Directed migration of human bone marrow mesenchymal stem cells in a physiological DC electric field." Eur. Cell Mater. 2011;22:344-358. DOI
9. McCaig CD, Song B, Rajnicek AM. "Electrical dimensions in cell science." J. Cell Sci. 2009;122(23):4267-4276. DOI
26. Babona-Pilipos R, Pritchard-Oh A, Popovic MR, Morshead CM. "Biphasic monopolar electrical stimulation induces rapid and directed galvanotaxis in adult subependymal neural precursors." Stem Cell Research & Therapy. 2015;6:67. DOI

    In undifferentiated mouse neural precursors, biphasic monopolar stimulation induced cathodal migration; biphasic bipolar stimulation did not. The study does not rule out biphasic pulses in general.

27. Poo M, Robinson KR. "Electrophoresis of concanavalin A receptors along embryonic muscle cell membrane." Nature. 1977;265:602–605. DOI

    Historical foundation: electric fields redistributed membrane receptors in living muscle cells, an early observation of electrophoretic redistribution of membrane proteins.

The dose · Direct current, repair & safety

Nerve and tissue repair, electrochemistry and safe-stimulation models. Dose and treatment methods require separate assessment.

6. Borgens RB, Vanable JW, Jaffe LF. "Bioelectricity and regeneration: initiation of frog limb regeneration by minute currents." J. Exp. Zool. 1977;200(3):403-416. DOI
10. Borgens RB, Jaffe LF, Cohen MJ. "Large and persistent electrical currents enter the transected lamprey spinal cord." PNAS. 1980;77(2):1209-1213. DOI
11. Leppik LP, Froemel D, Slavici A, et al. "Effects of electrical stimulation on rat limb regeneration, a new look at an old model." Sci. Rep. 2015;5:18353. DOI
12. Balint R, Cassidy NJ, Cartmell SH. "Electrical Stimulation: A Novel Tool for Tissue Engineering." Tissue Eng. Part B Rev. 2013;19(1):48-57. DOI
14. Baer ML, Colello RJ. "Endogenous bioelectric fields: A putative regulator of wound repair and regeneration in the central nervous system." Neural Regen. Res. 2016;11(6):861-864. DOI
19. Rouabhia M, Park H, Meng S, et al. "Electrical Stimulation Promotes Wound Healing by Enhancing Dermal Fibroblast Activity and Promoting Myofibroblast Transdifferentiation." PLoS One. 2013. DOI
20. Baer ML, Henderson SC, Colello RJ. "Elucidating the Role of Injury-Induced Electric Fields (EFs) in Regulating the Astrocytic Response to Injury in the Mammalian Central Nervous System." PLoS One. 2015;10(11):e0142740. DOI
21. Cheng N, Van Hoof H, Bockx E, et al. "The effects of electric currents on ATP generation, protein synthesis, and membrane transport of rat skin." Clin. Orthop. Relat. Res. 1982;(171):264-272. PMID: 7140077. PubMed
22. Konstantinou E, Zagoriti Z, Pyriochou A, Poulas K. "Microcurrent Stimulation Triggers MAPK Signaling and TGF-β1 Release in Fibroblast and Osteoblast-Like Cell Lines." Cells. 2020;9(9):1924. DOI
23. Reid B, Graue-Hernandez EO, Mannis MJ, Zhao M. "Modulating endogenous electric currents in human corneal wounds — a novel approach of bioelectric stimulation without electrodes." Cornea. 2011;30(3):338-343. DOI
24. Avendaño-Coy J, López-Muñoz P, Serrano-Muñoz D, et al. "Electrical microcurrent stimulation therapy for wound healing: A meta-analysis of randomized clinical trials." J. Tissue Viability. 2022;31(2):268-277. DOI
28. Peñin-Franch A, García-Vidal JA, Martínez CM, et al. "Galvanic current activates the NLRP3 inflammasome to promote Type I collagen production in tendon." eLife. 2022;11:e73675. DOI

    Preclinical study of percutaneous electrolysis: galvanic current activated NLRP3 and promoted type-I-collagen-mediated tendon regeneration in mice. Not equivalent to clinical evidence for Axomera.

29. Brighton CT, Black J, Friedenberg ZB, et al. "A multicenter study of the treatment of non-union with constant direct current." Journal of Bone and Joint Surgery, American Volume. 1981;63(1):2–13. DOI

    Multicentre clinical observation of bone healing in non-union with continuous direct current and immobilisation. A historical protocol with its own electrode and dose parameters, not an Axomera study.

30. Merrill DR, Bikson M, Jefferys JG. "Electrical stimulation of excitable tissue: design of efficacious and safe protocols." Journal of Neuroscience Methods. 2005;141(2):171–198. DOI

    Review of charge transfer, the electrode–tissue interface and electrochemical reversibility. A foundation for evaluating effective and safe stimulation protocols, not device-specific safety approval.

31. Shannon RV. "A model of safe levels for electrical stimulation." IEEE Transactions on Biomedical Engineering. 1992;39(4):424–426. DOI

    Model of safe stimulation levels based on charge and charge density. Its assumptions and stimulation waveform matter; it does not establish the safety of every direct-current procedure.

The site · Pathophysiology of indications

Tendon pathology, the local biochemical environment and the clinical classification of symptoms.

8. Shah JP, Phillips TM, Danoff JV, Gerber LH. "An in vivo microanalytical technique for measuring the local biochemical milieu of human skeletal muscle." J. Appl. Physiol. 2005;99(5):1977-84. DOI
15. Shah JP, Danoff JV, Desai MJ, et al. "Biochemicals associated with pain and inflammation are elevated in sites near to and remote from active myofascial trigger points." Arch. Phys. Med. Rehabil. 2008;89(1):16-23. DOI
32. Kraushaar BS, Nirschl RP. "Current Concepts Review – Tendinosis of the Elbow (Tennis Elbow). Clinical Features and Findings of Histological, Immunohistochemical, and Electron Microscopy Studies." Journal of Bone and Joint Surgery, American Volume. 1999;81(2):259–278. DOI

    Describes angiofibroblastic tendinosis in tennis elbow and distinguishes degenerative tendon changes from classical inflammatory tendinitis.

33. Alfredson H, Ljung BO, Thorsen K, Lorentzon R. "In vivo investigation of ECRB tendons with microdialysis technique—no signs of inflammation but high amounts of glutamate in tennis elbow." Acta Orthopaedica Scandinavica. 2000;71(5):475–479. DOI

    Microdialysis of the ECRB tendon in tennis elbow: elevated glutamate without the inflammatory markers studied. The linked paper concerns the elbow, not the Achilles tendon.

34. Cook JL, Purdam CR. "Is tendon pathology a continuum? A pathology model to explain the clinical presentation of load-induced tendinopathy." British Journal of Sports Medicine. 2009;43(6):409–416. DOI

    Continuum model from reactive tendinopathy through tendon disrepair to degenerative tendinopathy. A clinical framework, not proof of any particular treatment.

35. Weir A, Brukner P, Delahunt E, et al. "Doha agreement meeting on terminology and definitions in groin pain in athletes." British Journal of Sports Medicine. 2015;49(12):768–774. DOI

    International consensus on terminology and clinical classification of groin pain in athletes. Supports precise localisation and differential diagnosis.

Standard treatments · Context & comparison

Results and limitations of other treatments. These studies do not directly establish superiority of Axomera.

13. García Naranjo J, Barroso Rosa S, Loro Ferrer JF, et al. "A novel approach in the treatment of acute whiplash syndrome: Ultrasound-guided needle percutaneous electrolysis. A randomized controlled trial." Orthop. Traumatol. Surg. Res. 2017;103(8):1229-1234. DOI
16. Nnoaham KE, Kumbang J. "Transcutaneous electrical nerve stimulation (TENS) for chronic pain." Cochrane Database Syst. Rev. 2008;(3):CD003222. DOI
17. Shamji MF, De Vos C, Sharan A. "The Advancing Role of Neuromodulation for the Management of Chronic Treatment-Refractory Pain." Neurosurgery. 2017;80(3):S108-S113. DOI
18. Petersen EA, Slavin KV. "Peripheral nerve/field stimulation for chronic pain." Neurosurg. Clin. N. Am. 2014;25(4):789-797. DOI
36. Coombes BK, Bisset L, Vicenzino B. "Efficacy and safety of corticosteroid injections and other injections for management of tendinopathy: a systematic review of randomised controlled trials." The Lancet. 2010;376(9754):1751–1767. DOI

    Systematic review: corticosteroid injections can help in the short term; intermediate and long-term outcomes vary by indication and can be less favourable. No direct comparison with Axomera.

37. Bisset L, Beller E, Jull G, et al. "Mobilisation with movement and exercise, corticosteroid injection, or wait and see for tennis elbow: randomised trial." BMJ. 2006;333:939. DOI

    Tennis-elbow RCT: early benefit from corticosteroid injection, followed by frequent recurrence. Of 65 initially successful treatments, 47 (72%) subsequently regressed—a study-specific, not universal, recurrence rate.

38. Dean BJF, Lostis E, Oakley T, et al. "The risks and benefits of glucocorticoid treatment for tendinopathy: A systematic review of the effects of local glucocorticoid on tendon." Seminars in Arthritis and Rheumatism. 2014;43(4):570–576. DOI

    Systematic review of local glucocorticoids and tendon tissue, including effects on tenocytes, collagen and mechanical properties. Experimental findings should not be generalised to every clinical application.

Our publications · Axomera / PBCS

Published descriptions of the method and clinical case series. Observational reports do not replace randomised controlled trials.

7. Molsberger A, McCaig CD. "Percutaneous direct current stimulation — a new electroceutical solution for severe neurological pain and soft tissue injuries." Med. Devices (Auckl.). 2018;11:205-214. DOI

   Description of the percutaneous direct-current method and clinical applications. Not a randomised efficacy study.

39. Molsberger A, McCaig CD. "Percutaneous Bioelectric Current Stimulation for Chronic Cluster Headache – A Possible Transformative Approach to Cluster Headache." Journal of Pain Research. 2020;13:817–828. DOI

    Retrospective case series of 20 patients with chronic cluster headache. Reports clinical outcomes with PBCS, without sham control or randomisation; the authors call for controlled trials.