PEMF therapy is used in both human and veterinary medicine to treat a variety of ailments. We unpack the clinical evidence, different device parameters and claims that have caused confusion.

Pulsed electromagnetic field (PEMF) therapy is a non-invasive electrotherapy that uses an electromagnetic waveform delivered by antenna. PEMF devices have been approved by the US Food and Drug Administration (FDA) to treat non-union fractures, and cleared to treat soft tissue post-operative pain and edema.¹

PEMF therapy devices have been in use for more than a century.¹ During the 1930s, a vacuum tube-based diathermy machine used to deliver heat deep into tissue was modified by changing the duty cycle to not produce heat. This new non-thermal device was discovered to have therapeutic effects in pain reduction and wound healing. In the 1970s, orthopedic researchers and clinicians began to surgically implant electrodes into bone to treat non-healing fractures.^2,3 Shortly thereafter, non-invasive antennas were used to pulse electromagnetic fields across non-healing fractures in dogs and humans.⁴ This gave rise to low-powered PEMF devices called bone growth stimulators (BGS), later approved by the FDA.⁵ During the 20th century, more and more research and clinical evidence led to a greater understanding of how PEMF works.^6,7

Differentiating PEMF devices

Several parameters determine the mechanism of action, efficacy, and safety of each device, including the electromagnetic waveforms they emit, the size and geometry of the antenna, and the difference in treatment applications. These combined variabilities necessitate the need for validation of each individual PEMF type device.

Different PEMF devices have different magnetic fields that can vary from less than one gauss to several thousand gauss. A gauss is a measure of magnetic induction, also known as magnetic flux density. As defined by today’s International Systems of Units, a tesla corresponds to 10,000 gauss.

• Devices generating biological effects from magnetic fields are usually categorized as low frequency, with less than 1,000 Hz carrier frequency.
• High frequency devices with greater than 1,000 Hz carrier frequency usually produce biological effects stemming from electric fields.

Additionally:

• Targeted PEMF (tPEMF) devices have waveforms specifically produced to deliver energy to tissue and modulate biologically signalled cascades.
• Non-targeted PEMF devices employ waveforms that are not designed to enhance specific biological effects, and are less efficient.

Increased calcium ion (Ca2+) signalling has been recognized as an important factor supporting the clinical effects of tPEMF as well as other PEMF technologies and predecessors.^8,9 PEMF exposure releases intracellular calcium, which in turn enhances binding of Ca2+ to calmodulin (CaM).

Targeted PEMF Mechanism of action

Targeted PEMF induces downstream production of nitric oxide (NO). Dr. Louis Ignarro and colleagues described the role of NO in biology as a gaseous signalling molecule, particularly about its cardiological effects.10 In 1998, they were awarded the Nobel Prize in Physiology or Medicine for their research.^10,11,12 NO is an important homeostasis signalling molecule as it can function as a vasodilator and also influence the nervous and immune systems.^13,14 Targeted PEMF enhances NO production which clinically reduces pain, edema, and inflammation by reducing programmed cell death, promoting blood vessel dilation, and enhancing circulation.^{1,9,15,16,17,18,19,20}

Calcium binds with CaM when increased concentrations of Ca2+ are present in the cytoplasm. Rapid bursts of NO are produced when Ca2+ to CaM binding activates constitutive nitric oxide synthase (cNOS). NO binds to soluble guanylyl cyclase and increases production of cyclic guanosine monophosphate (cGMP). Anti-inflammatory responses, enhanced blood flow, and production of growth factors are activated following enhanced NO and cGMP — all required for tissue repair and healing. After tissue injury, surgical or traumatic, a complex inflammatory cascade occurs to avoid infection, enhance tissue remodeling, and start tissue healing. Concurrently, an anti-inflammatory cascade is initiated, decreasing inflammation, increasing cGMP, and releasing growth factors to bolster vascularization, tissue regeneration, and remodelling.

Heat shock proteins (HSP) are inducible proteins that are expressed under stressful conditions but are considered cytoprotective and prevent apoptosis.²¹ A specific group of HSPs — HSP70, important in protein folding — are induced by tPEMF therapy, also imperative for tissue healing.^22,23,24

Research supporting PEMF and TPEMF efficacy

• Both acute and chronic inflammation often add to pain and edema. Several studies support the effectiveness of PEMF and tPEMF to combat pain, edema, and inflammation.

» One post-surgical breast surgery study that used a continuous PEMF device for seven days reported significantly lower visual analog pain (VAS) scores and ingestion of fewer narcotic pain pills.²⁵

» Targeted PEMF has been used in four doubleblind, randomized, placebo-controlled research studies in humans undergoing breast augmentation, breast reduction, bilateral mastectomy and reconstruction, and mastectomy with transverse rectus abdominus reconstruction.^19,20,26 Targeted PEMF treatment, compared to placebo treatment, significantly reduced pain by 50%, edema by over 40%, interleukin-1 beta by 40%, and narcotic pain ingestion by 50% post-operatively.²⁰

• Research has also documented that PEMF enhances vascular function and wound repair.

» One study in rats demonstrated that PEMF treatment accelerated new blood vessel growth five-fold in an arterial flap transfer.²⁷

» In a subsequent study in rats, arterial blood supply to a tissue flap was cut off and PEMF was applied. The sham cohort had virtually complete flap failure while PEMF-treated animals exhibited significant vascularization and virtually complete flap survival.²⁸ PEMF is effective in wound healing due to enhanced vascularization and tissue perfusion.

• PEMF devices that are FDA-cleared are safe, effective treatments for chronic wounds, and several studies demonstrate that treatment accelerated the healing of chronic pressure wounds such as diabetic leg and foot ulcers as well as pressure sores.^29,30,31,32

In a randomized, clinical trial involving paraplegic veterans with sacral ulcers, one 30-minute daily treatment with PEMF every weekday for one month resulted in 64% wound closure, versus a 7% increase in wound size in the sham-treated veterans.^30,33

• Recently, a targeted PEMF device called The Assisi Loop® as been used in veterinary patients to assess efficacy of post-operative pain reduction and wound healing.

» In 2018, a randomized, double-blind, placebo-controlled study was conducted on dogs with acute, severe intervertebral disc extrusion and paraplegia being treated with spinal decompression surgery. Dogs receiving targeted PEMF therapy exhibited significant reductions in surgical incision pain, lower concentrations of inflammatory spinal fluid markers, and improved proprioceptive function compared to sham controls.³⁴

» The Assisi Loop® also underwent a second randomized, double-blind, sham-controlled study evaluating its effects on dogs with acute intervertebral disc extrusion and paraplegia treated with spinal decompression surgery. Dogs receiving tPEMF therapy had significantly improved visual analogue scores (VAS) on wound healing and wound evaluation (WES) scoring. Interestingly, sham-treated patients had higher numbers of owner-administered pain medication compared to tPEMF-treated dogs.³⁵

PEMF has demonstrated biological and clinical effects for a variety of conditions. Advancement of the field has shown PEMF’s usefulness in treating pain, inflammation, bone healing, and acute and chronic wounds. It is non-invasive and safe and can be used as a stand-alone or adjunctive treatment modality to treat veterinary patients with a variety of conditions.³⁶

¹Strauch, B., Herman, C., Dabb. R., Ignarro, L. J., Pilla, A. A., 2009. Evidence-based use of pulsed electromagnetic field therapy in clinical plastic surgery. Aesthet Surg J 29, 135-143.

²l-Mandeel, M., Watson, T, 2008. Pulsed and Continuous short-wave therapy, 12th Ed. Elsevier, New York.

³Paterson, D.C., Carter, R.F., Maxwell, G.M., Hillier, T.M., Ludbrook, J., Savage, J.P., 1977. Electrical bonegrowth stimulation in an experimental model of delayed union. Lancet 1, 1278-1281.

⁴Bassett, C.A., Pilla, A.A., Pawluk, R.J., 1977. A non-operative salvage of surgically resistant pseudarthroses and non-unions by pulsing electric fields. A preliminary report. Clin Orthop Relat Res, 128-143.

⁵Bassett, C.A., Mitchell, S.N., Gaston, S.R., 1982 Pulsing electromagnetic field treatment in un-united fractures and failed arthrodesis. JAMA 247, 623-628.

⁶Pilla, A.A., 2006. Biological and medical aspects of electromagnetic fields. CRC Press, Boca Raton, FL.

⁷Pilla, A.A., 2013. Nonthermal electromagnetic fields: from first messenger to therapeutic applications. Electromagn Biol Med 32, 123-136.

⁸Brighton, C.T., Wang, W., Seldes, R., Zhang, G., Pollack, S.R., 2001 Signal transduction in electrically stimulated bone cells. J Bone Joint Surg Am 83-A, 1514-1523.

⁹Pilla, A.A., Fitzsimmons, R., Muesham, D., Wu, J., Rhode, C., Casper, D., 2011. Electromagnetic fields as first messenger in biological signaling: Application to calmodulin-dependent signaling in tissue repair. Biochem Biophys Act 1810, 1236-1245.

¹⁰Ignarro, L.J., 1990. Biosynthesis and metabolism of endothelium-derived nitric oxide. Annu Rev Pharmacol Toxicol 30, 535-560.

¹¹Ignarro, L.J., Lippton, H., Edwards, J.C., Baricos, W.H., Hyman, A.L., Kadowitx, P.J., Gruetter, C.A., 1981. Mechanisms of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside and nitric oxide: evidence for involvement of S-nitrosothiols as active intermediates. J Pharmacol Exp Ther 218, 739-749.

¹²Ignarro, L.J., Buga, G.M., Wood, K.S., Byrnes, R.E., Chaudhuri, G., 1987. Endothelium derived relaxing factor produced and released from artery and vein is nitric oxide. Proc Natl Acad Sci USA 84, 9265-9269.

¹³Bogdan, C., 2001. Nitric oxide and the immune response. Nat Immunol 2, 907-916.

¹⁴Calabrese, V., Mancuso, C., Calvani, M., Rizzarelli, E., Butterfield, D.A., Stella, A.M., 2007. Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity. Nat Rev Neurosci 8, 766-775.

¹⁵Bragin, C.T., Statom, G.L., Hagberg, S., Nemoto, E.M., 2014. Increases in microvascular perfusion and tissue oxygenation via pulsed electromagnetic fields in the healthy rat brain. J Neurosurg, 109.

¹⁶Pilla, A.A., 2012. Electromagnetic fields instantaneously modulate nitric oxide signaling in challenged biological systems. Biochem Biophys Res Commun 426, 330-333.

¹⁷Pena-Phillippedes, J.C., Yang, Y., Bragina, O., Hagberg, S., Nemoto, E., Roitbak, T., 2014. Effect of pulsed electromagnetic field on infarct size and inflammation after cerebral ischemia in mice. Translational Stroke Res 5, 491-500.

¹⁸Rasouli, J., Le khraj, R., White, N.M., Flamm, E.S., Pilla, A.A., Strauch, B., Casper, D., 2012. Attenuation of interleukin-1beta by pulsed electromagnetic fields after traumatic brain injury. Neuroscience Letters 519, 4-8.

¹⁹Rohde, C., Chiang, A., Adipoju, O., Casper, D., Pilla, A.A., 2010. Effects of pulsed electromagnetic fields on interleukin-1 beta and postoperative pain: a double-blind, placebo-controlled, pilot study in breast reduction patients. Plast Reconstr Surg 125, 1620-1629.

²⁰Rohde, C.H., Taylor, E.M., Alonso, A., Ascherman, J.A., Hardy, K.L., Pilla, A.A., 2015. Pulsed Electromagnetic Fields Reduce Postoperative Interleukin-1beta, Pain, and Inflammation: A Double-Blind, Placebo-Controlled Study in TRAM Flap Breast Reconstruction Patients. Plast Reconstr Surg 135, 808e-817e.

²¹Robertson, J.A., Thomas, A.W., Bureau, Y., Prato, F.S., 2007. The influence of extremely low frequency magnetic fields on cytoprotection and repair. Bioelectromagnetics 28, 16-30.

²²DiCarlo, A.L., Farrell, J.M., Litovitz, T.A., 1999. Myocardial protection conferred by electromagnetic fields. Circulation 99, 813-816.

²³Rodriguez de la Fuente, A.O., Alcocer-Gonzalez, J.M., Antonio Heredia-Rojas, J., Balderas- Candanosa, I., Rodriguez-Flores, L.E., Rodriguez-Padilla, C., Tamez- Guerra, R.S., 2009. Effect of 60 Hz electromagnetic fields on the activity of hsp70 promoter: an in vitro study. Cell Biol Int 33, 419-423.

²⁴Rodriguez-De la Fuente, A.O., Alcocer-Gonzalez, J.M., Heredia-Rojas, J.A., Rodriguez-Padilla, C., Rodriguez-Flores, L.E., Santoyo-Stephano, M.A., Castaneda-Garza, E., Tamez-Guerra, R.S., 2012. Effect of 60 Hz electromagnetic fields on the activity of hsp70 promoter: an in vivo study. Cell Biol Int Rep (2010) 19, e00014.

²⁵Rawe, I.M., Lowenstein, A., Barcelo, C.R., Genecov, D.G., 2012. Control of postoperative pain with a wearable continuously operating pulsed radiofrequency energy device: a preliminary study. Aesthetic Plast Surg 36, 458-463.

²⁶Heden, P., Pilla, A.A., 2008. Effects of pulsed electromagnetic fields on postoperative pain: a double-blind randomized pilot study in breast augmentation patients. Aesthetic Plast Surg 32, 660-666.

²⁷Roland, D., Ferder, M., Kothuru, R., Faierman, T., Strauch, B., 2000. Effects of pulsed magnetic energy on a microsurgically transferred vessel. Plast Reconstr Surg 105, 1371-1374.

²⁸Strauch, B., Patel, M.K., Navarro, J.A., Berdichevsky, M., Yu, H.L., Pilla, A.A., 2007. Pulsed magnetic fields accelerate cutaneous wound healing in rats. Plast Reconstr Surg 120, 425-430.

²⁹Weber, R.V., Navarro, A., Wu, J.K., Yu, H.L., Strauch, B., 2004. Pulsed magnetic fields applied to a transferred arterial loop support the rat groin composite flap. Plast Reconstr Surg 114, 1185-1189.

³⁰Kloth, L., Berman, J., Sutton, C., Jeutter, D., Pilla, A., Epner, M., 1999. Effect of pulsed radio frequency stimulation on wound healing: a double-blind pilot clinical study, Electricity and magnetism in biology and medicine. Springer, pp. 875-878.

³¹Mayrovitz, H.N., Larsen, P.B., 1995. A preliminary study to evaluate the effect of pulsed radio frequency field treatment on lower extremity peri-ulcer skin microcirculation of diabetic patients. Wounds 7, 90-93.

³²Salzberg, C.A., Cooper-Vastola, S.A., Perez, F., Viehbeck, M.G., Byrne, D.W., 1995. The effects of non-thermal pulsed electromagnetic energy on wound healing of pressure ulcers in spinal cord-injured patients: a randomized, double-blind study. Ostomy Wound Manage 41, 42-44, 46, 48.

³³Stiller, M.J., Pak, G.H., Shupack, J.L., Thaler, S., Kenny, C., Jondreau, L., 1992. A portable pulsed electromagnetic field (PEMF) device to enhance healing of recalcitrant venous ulcers: a double-blind, placebo-controlled clinical trial. Br J Dermatol 127, 147-154.

³⁴Zidan, N., Fenn, J., Griffith, E., Early, P.J., Mariani, C.L., Munana, K.R., Guevar, J., Olby, N., 2018. The effect of electromagnetic fields on postoperative pain and locomotor recovery in dogs with acute, severe thoracolumbar intervertebral disc extrusion: a randomized placebo-controlled, prospective clinical trial. J Neurotrauma.

³⁵Alvarez, L.X., McCue, J., Lam, N.K., Askin, G., Fox, P.R., 2018. Effect of Targeted Pulsed Electromagnetic Field Therapy on Canine Postoperative Hemilaminectomy: A Double- Blind, Randomized, Placebo-Controlled Clinical Trial. JAAHA Mar/Apr 2019, 83-91.

³⁶Gaynor, J.S., Hagberg, S, Gurfein, B.T., 2018. Veterinary Applications of Pulsed Electromagnetic Field Therapy. Research in Veterinary Science May 2018.