Topical DMSO for Pain

By Dónal P. O'Mathúna, PhD Dr. O'Mathúna is a lecturer in Health Care Ethics, the School of Nursing, Dublin City University, Ireland; he reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study.

DMSO (dimethyl sulfoxide) is a small organic compound originally used for its solvent properties. Prior to the 1960s it was widely used in the wood and paper industry. Dr. Stanley Jacob, an organ transplant surgeon, noticed in 1961 that DMSO could be used to preserve organs,1 and it continues to be used when storing biological tissues and organs to this day. Dr. Jacob noticed that DMSO penetrated the skin, rapidly leading to a garlic-like taste and odor on people's breath; thus began a life-long research interest for Dr. Jacob. He continues to advocate widespread use of DMSO, which he maintains is as useful as aspirin.2

The biological properties of DMSO have been broadly investigated. During the 1970s, many veterinary and human applications were examined, which ultimately gave rise to FDA approval for DMSO as a treatment for at least one clinical entity, that being interstitial cystitis. This condition primarily affects women who typically present with bladder pain and difficulties with urination. Treatment consists of instillation of DMSO into the bladder using a catheter. Treatment, though uncomfortable, is effective.3 The focus of this review is on the more general use of DMSO in treating various painful conditions. For these, DMSO is primarily used topically.

Biochemistry

Chemically, DMSO is called an amphipathic molecule, meaning it is compatible with both polar and non-polar chemicals.4 This allows it to both dissolve water-insoluble compounds and mix well with water. For this reason, it is widely used as a solvent in a variety of chemical and pharmaceutical settings. These properties also allow DMSO to readily cross tissue membranes, carrying with it any dissolved compounds.

Mechanism of Action

DMSO reversibly crosses biological membranes without damaging them, including the blood-brain barrier.3 This property has led to its use as a vehicle for drug therapy. The absorption of a wide range of drugs and other small molecular weight compounds can thus be facilitated, though not larger molecules like insulin and other proteins.5 This also underlies concerns about the transfer of undesirable contaminants across these membranes.4

A large number of biological studies has been carried out with DMSO. These studies have established that DMSO impacts a wide range of physiological processes, including the inflammatory process, the cell cycle, apoptosis, and lipid metabolism.4 The precise contribution that each of these makes to a possible analgesic effect is not known. DMSO is also known to be a free radical scavenger, particularly of the hydroxyl radical. It is believed that DMSO may relieve pain by inactivating the toxic oxygen radicals produced by various types of tissue injury.6

Clinical Studies

The topical use of DMSO to treat pain is reported to be supported by many studies. However, a highly positive review only cited studies published in the 1960s.1 A search of PubMed and the Cochrane Library revealed few, high-quality studies. The only painful condition in which DMSO was studied in a number of controlled studies was complex regional pain syndrome type 1 (CRPS I).7 CRPS I is a heterogeneous syndrome diagnosed after other painful conditions have been excluded. It is characterized by pain originating with an initial noxious event that proceeds to pain disproportionate to the initial injury.8 This leads to symptoms of diffuse pain, spreading edema, temperature disturbances, and restricted range of motion.6

Many different treatments, pharmacological and non-pharmacological, have been recommended for CRPS I.7 A 1997 review of CRPS therapy found 26 controlled trials involving 17 different treatments.8 Many of these had no controlled studies to support their use, but topical application of DMSO was found to have "limited support" in relieving pain. This conclusion was based on one clinical trial, which a more systematic review in 2002 evaluated as being of low quality.9 The trial randomly assigned 26 patients to either 50% aqueous DMSO or a regional intravenous sympathetic block.10 DMSO was applied four times daily for three weeks. Significant improvements were found for pain and daily activity scores compared to baseline (P < 0.05), but no differences were found between the two groups.

The 2002 systematic review located one other study that was evaluated as being of high quality.9 This double-blind, randomized study assigned 32 subjects to either 50% DMSO cream or placebo cream.11 Subjects also received physical therapy as pain would allow. After two months, both groups showed significant improvements in pain and overall symptom scores compared to baseline. The overall symptom score was significantly better for the DMSO group (P < 0.01).

A 2003 double-blind, randomized study was conducted with 146 subjects.6 One group applied 50% DMSO cream to the affected area five times daily and took one effervescent placebo tablet three times daily. The second group applied a placebo cream five times daily and took one 600 mg N-acetylcysteine (NAC) effervescent tablet three times daily. NAC is another free radical scavenger used to treat CRPS I. Subjects in both groups also received standard oral analgesics as required, along with standard occupational or physical therapy. Outcome measurements included those for pain, temperature, and range of motion. These were evaluated at baseline and after six, 17, 32, and 52 weeks. Subjects were offered the opportunity to switch groups at 17 weeks. No significant differences were found between the two groups for pain reduction. Both groups had a clinically relevant reduction in an overall impairment level score. This study also referenced an open trial published in Dutch, which found reduced pain in CRPS I patients using 50% DMSO cream.

A small number of additional studies were located in which topical DMSO was used to treat pain. A Cochrane review of nonsteroidal anti-inflammatory drugs for the treatment of tennis elbow identified one study using DMSO. A randomized, double-blind controlled study involved 102 subjects with either tennis elbow or rotator cuff tendinitis.12 For one year, patients used either 70% DMSO aqueous solution or 5% DMSO aqueous solution. The latter was used as a placebo so that patients would still detect the distinctive DMSO taste and odor. Measurements of pain, tenderness, swelling, and range of motion showed no significant differences between the groups.

A German study examined topical DMSO in another painful condition, gonarthrosis (knee joint damage that is not advanced).13 This double-blind controlled study randomized 112 patients to either 25% DMSO gel or a placebo gel. After three weeks, patients using DMSO had significantly improved scores over placebo for pain during everyday activities (P = 0.019), pain at rest (P = 0.015), and pain on palpation (P = 0.029). Pain diaries also reflected significant improvements.

Adverse Effects

Topical application of DMSO is generally well tolerated, although mild transient local burning, rash, and pruritis have been reported.4 The most frequently reported adverse effect with topical DMSO is the distinctive garlic-like taste and breath odor. This arises within minutes of applying DMSO and is caused by sulfur meta-bolites. Much of the controversy surrounding DMSO arose after a woman in Ireland died from an allergic reaction to DMSO in 1965.1 Headache, drowsiness, and other flu-like symptoms have also been reported occasionally.14

Drug Interactions

Evidence from animal studies has raised concerns about drug interactions, but specific reports were not found. DMSO enhances the topical absorption of many drugs. Use of DMSO along with other topical drugs will likely increase their systemic concentrations.

Formulation

DMSO is available as aqueous solutions, gels, or creams. Most studies were conducted with 50% preparations, although formulations are available in various concentrations.

Conclusion

Although widely recommended as a topical analgesic for humans and animals, relatively few studies supporting this indication were located. These studies in general revealed some effectiveness in relieving the pain of CRPS I. However, some of the studies did not use a placebo, but found DMSO to be as effective as other treatments of uncertain effectiveness. DMSO was not found to be effective with all forms of pain for which it has been tested. Studies reported few adverse effects, other than the disagreeable taste and breath odor.

Recommendation

Some generalized pain conditions do not respond well to conventional analgesics. Given that topical DMSO has been somewhat effective in treating CRPS I, and that it is generally well tolerated, use on a trial basis can be suggested. However, patients should be warned of the taste and odor on their breath, which may make its use intolerable. Patients should be alerted to the importance of using pharmaceutical grade DMSO. Although less expensive, industrial grade DMSO can contain impurities that will be rapidly absorbed into the body and may cause adverse reactions.14 Similarly, the skin should be cleaned thoroughly before applying DMSO to prevent absorption of skin contaminants. Patients should also be given information about other pain-relieving strategies that may complement the use of DMSO or other analgesics.

References

1. Muir M. DMSO: Many uses, much controversy. Altern Complement Ther 1996;2:230-235.

2. Jacob SW. Current status of dimethyl sulfoxide (DMSO). Available at www.dmso.org/articles/information/jacob.htm. Accessed on Oct. 19, 2005.

3. Rössberger J, et al. Critical appraisal of dimethyl sulfoxide treatment for interstitial cystitis: Discomfort, side-effects and treatment outcome. Scand J Urol Nephrol 2005;39:73-77.

4. Santos NC, et al. Multidisciplinary utilization of dimethyl sulfoxide: Pharmacological, cellular, and molecular aspects. Biochem Pharmacol 2003;65:1035-1041.

5. Jacob SW, Herschler R. Pharmacology of DMSO. Cryobiology 1986;23:14-27.

6. Perez RS, et al. The treatment of complex regional pain syndrome type I with free radical scavengers: A randomized controlled study. Pain 2003;102:297-307.

7. Quisel A, et al. Complex regional pain syndrome: Which treatments show promise? J Fam Pract 2005;54:599-603.

8. Kingery WS. A critical review of controlled clinical trials for peripheral neuropathic pain and complex regional pain syndromes. Pain 1997;73:123-139.

9. Forouzanfar T, et al. Treatment of complex regional pain syndrome type I. Eur J Pain 2002;6:105-122.

10. Geertzen JH, et al. Reflex sympathetic dystrophy: Early treatment and psychological aspects. Arch Phys Med Rehabil 1994;75:442-446.

11. Zuurmond WW, et al. Treatment of acute reflex sympathetic dystrophy with DMSO 50% in a fatty cream. Acta Anaesthesiol Scand 1996;40:364-367.

12. Percy EC, Carson JD. The use of DMSO in tennis elbow and rotator cuff tendonitis: A double-blind study. Med Sci Sports Exerc 1981;13:215-219.

13. Eberhardt R, et al. DMSO in patients with activated gonarthrosis. A double-blind, placebo-controlled phase III study. Fortschr Med 1995;113:446-450.

14. DMSO (dimethylsulfoxide). Available at www.naturaldatabase.com. Accessed on Oct. 19, 2005.