ARDS is char -
acterized by interstitial edema, low paO
2, rising paCO2, and complete opacification TABLE 2.1
Survival Rates of Hypoxemic Rats Exposed to 3 min of Pure Nitrogen in 
a Closed Chamber Pretreated with DMSO, Doxapram, and Ethamivan
Effects of DMSO on Experimental Hypoxemia in Rats
Agent Survivors/Total Survival, % P Value
DMSO 18/20 90 <0.0025
Saline 3/20 15
Doxapram 18/20 90 <0.0025
Saline 2/20 10
Ethamivan 6/20 30 >0.4
Saline 3/20 15
Note:  See te xt for details.34 Dimethyl Sulfoxide (DMSO) in Trauma and Disease
of both lung fields on chest x-ray. A 10% DMSO solution was given intravenously to 
three patients nearing death presenting with ARDS who were refractory to classical therapy. All three patients showed marked improvement 1  h after the application of DMSO with respect to oxygen saturation, increased paO
2, and lowered paCO2. One patient showed a dramatic improvement of the chest x-ray, which resolved over a period of 1 week. It was concluded by the author of the study that DMSO use in ARDS merits further investigation. 130
A model of ARDS using formylated tripeptide formyl-norleucyl-leucyl-  
phenylalanine (FNLP) was instilled intratracheally into hamsters to induce acute edematous lung injury. Intratracheal FNLP is time dependent and dose dependent and increases neutrophils to create neutrophil alveolitis and leak of intravenously injected albumin into the extravascular lung space (lung leak). 131
It was observed that treatment with 0.20% DMSO significantly decreased neutro -
phil alveolitis and lung leak in hamsters following FNLP intratracheally, possibly by inhibiting neutrophil chemotaxis. 131
DMSO is reported to increase hypoxic tolerance of brain slices under hypoxic  or 
ischemic  conditions. After the induction of hypoxia or ischemia in the CA1 region 
of hippocampal slices of adult guinea pigs, evoked potentials recording showed that during superfusion with artificial CSF containing DMSO 14.1 mmol/L the latency of anoxic terminal negativity was markedly improved when compared to the control brain slices, demonstrating a neuroprotective effect of DMSO on ischemia/hypoxia. 132
EXPERIMENTAL BLUNT CHEST TRAUMA
Blunt chest trauma is an injury to the chest caused by an impact from a blunt object. Blunt chest trauma puts multiple adjoining structures at risk of injury. This type of injury can involve cardiac contusion, cardiovascular injury, and pulmonary lacera -
tions. Traffic accidents are the most frequent cause of blunt chest trauma and cardiac contusions due to acceleration–deceleration and usually involving a direct blow to the chest. Many other causes can result in blunt chest trauma, including a violent fall, explosion, aggression, and various types of high-risk sports. The majority of blunt chest injuries can be classified into three types: minor chest 
wall injuries, major but stable chest wall injuries, and flail chest injuries. The first two chest injuries can involve fracture of the bony chest wall or no fracture. Flail chest is a life-threatening medical condition where the rib cage breaks under extreme stress, damaging ribs in multiple places where they become detached from the rest of the chest wall moving independently of the rib cage. To study traumatic pulmonary contusion, DMSO was compared to the powerful anti-
inflammatory agent dexamethasone using a designed thoracic trauma model in rats. 132a 
DMSO (1.2 g/kg) and dexamethasone (10 mg/kg) were given intraperitoneally 15 min prior to injury. The effects of blunt trauma to lung tissue was examined biochemically and histopathologically. A number of pathologic signs were observed in all animal 
groups following blunt trauma, including alveolar edema, congestion, and pulmonary 
parenchymal hemorrhage. 132a
The levels of oxidative stress predictors malondialdehyde and nitric oxide were 
lower with both dexamethasone- or DMSO-treated animals when compared with 35 DMSO in Basic Pharmacology
untreated blunt chest trauma animals. This finding indicated the well-known antioxi -
dant properties of DMSO and dexamethasone in inflammatory conditions. However, 
further analysis revealed that only DMSO-treated animals prevented further injury by decreasing neutrophil infiltration and endothelial cell injury of blood vessels near the injury site following the lung contusion. 132a
As we have reviewed in Chapter 8, the production of excessive free radicals and 
the release of local inflammatory mediators including cytokines such as interleu -
kin 6, tumor necrosis factor- α, and nitric oxide are generally the culprits responsible 
for the deadly pathologic cascades seen following traumatic brain injury. DMSO is a powerful free radical scavenger and effective anti-inflammatory agent that is able to quell the cytokine storm  seen after the blunt chest trauma. In addition, 
these cytokines can lead to complications affecting immunosuppression, leading to multi organ damage. 72
AUTOPHAGY
Autophagy is a dynamic process of subcellular component degradation, which has sparked a great deal of interest in the last decade since it is now recognized to be involved in various developmental processes affecting certain disorders, including neurodegeneration and cancer. 133
Autophagy is a basic catabolic mechanism in eukaryotes that involves cell deg -
radation of unnecessary or dysfunctional cellular components in the cytoplasm and sequesters these into double-membrane vesicles where they are delivered to the lyso -
some/vacuole for breakdown and eventual recycling. 134 The breakdown of cellular 
components can ensure cellular survival during nutrient starvation by maintaining cellular energy levels. 134 Normally, when autophagy is regulated, synthesis, degrada -
tion, and recycling of these cellular components are maintained. Targeted cytoplas -
mic components are isolated from the rest of the cell within the autophagosomes, which are then fused with lysosomes and degraded or recycled. The relevance of autophagy in disease is seen as an adaptive response to survival, but in certain cir -
cumstances, autophagy has also been described as a promoter of cell death and morbidity. 134
Three different forms of autophagy have been described. These are macroau -
tophagy, microautophagy, and chaperone-mediated autophagy (CMA).135
Autophagy can function as a cytoprotective mechanism, but it also has the 
capacity to cause cell death. Autophagy is a major mechanism for degrading long-lived cytosolic proteins and the only known pathway for degrading organelles. 136 
Autophagy is activated by many forms of stress, including nutrient and energy starvation, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, and infections. Autophagy recycles amino acids and fatty acids to produce energy while removing damaged cell components, thereby playing an essential role in cell survival and intracellular surveillance mechanism, which is indispens -
able for maintaining cell health. When this process is abnormal, autophagy leads to cell death. 137
CMA is a selective type of autophagy by which specific cytosolic proteins are 
sent to lysosomes for degradation.36 Dimethyl Sulfoxide (DMSO) in Trauma and Disease
The chemical chaperones in the cytosol normally unfold substrate proteins prior 
to their translocation across the lysosomal membrane, but when this process is aber -
rant, DMSO administration, acting a chemical chaperone, may induce CMA and 
exert a protective effect toward the cell’s survival (see also Chapter 1, “DMSO as a Chemical Chaperone”). For example, DMSO appears to have a beneficial role in inducing autophagy as 
a chemical chaperone by reducing free fatty acid–induced hepatic fat accumulation in a dose-dependent manner. 138 Treatment with 0.01% DMSO for 16 h significantly 
reduced palmitate-induced triglyceride accumulation in rat hepatocytes.138 This 
effect by DMSO was postulated to result from the downregulation of the ATF4/AKT1 pathway, a stress-induced transcription factor that is overexpressed in many cancers and is an important mediator of the unfolded protein response. 138,139
DIURESIS
DMSO is a powerful diuretic when used intravenously. A fivefold increase in urine excretion as compared to saline controls is seen after 1 h of 40% DMSO IV given at 2.5 g/kg in dogs with spinal cord trauma. 127 In rats, DMSO given topically five times 
daily increased urine volume 10-fold.140 The brisk diuretic response to 40% DMSO 
infusion has been seen in patients treated for high intracranial pressure secondary to head injury. 141 Diuresis after high doses of DMSO is accompanied by electro -
lyte changes involving sodium and potassium excretion,142 but these changes can be 
minimized by reducing excessive DMSO fluid overload and by carefully monitoring electrolytes after high and repeated dosing with DMSO. 143
These collective findings suggest that DMSO merits clinical evaluation as a 
potent and primary treatment when diuresis is indicated in water retention for such conditions as cirrhosis, acute or chronic renal failure, nephrotic syndrome, and con -
gestive heart failure. CHOLINESTERASE INHIBITION
DMSO is reported to inhibit the isolated and innervated guinea pig atrium following incubation in a bath mimicking the action of neostigmine by lowering the vagal thresh -
old to electrical stimulation. 144 It was found that this action by DMSO at doses of 0.01–1.0 
mol/L incubated for 30 min  in the guinea pig atrium bath was able to inhibit erythro -
cyte cholinesterase, the enzyme that breaks down the neurotransmitter acetylcholine.144
The cholinesterase inhibitory activity by DMSO could reasonably target the low -
ering of high blood pressure, bronchoconstriction, and intraocular pressure. Despite their annoying gastrointestinal effects, cholinesterase inhibitors are also used in treat -
ing the symptoms of Alzheimer’s disease,
138 a disorder where DMSO dose adjustment 
could avoid the gastrointestinal side effects seen with stronger cholinesterase drugs. This aspect of DMSO therapy will be more fully discussed in Chapter 8. DMSO was studied at the neuromuscular junction of the frog cutaneous pectoris 
using electrophysiological techniques and found to elevate the amplitude of extra -
cellularly recorded miniature end-plate potentials as well as the time constant of their monoexponential decay. These findings indicated that DMSO partially blocked 37 DMSO in Basic Pharmacology
cholinesterase activity and the presynaptic action of acetylcholine release,145 an 
action that has been confirmed on a variety of invertebrate muscles.146
SOLVENT ACTION
DMSO is a solvent for many aromatic and unsaturated hydrocarbons as well as inor -
ganic salts and nitrogen-containing compounds. This ability to act as a universal 
solvent may be due to DMSO’s high dielectric constant due to the polarity of the sulfur–oxygen bond. DMSO has been shown to carry physostigmine and phenylbutazone through the 
skin of the rat. Moreover, there  is evidence that DMSO enhances the percutaneous 
absorption of many other compounds, including steroids, vasoconstrictors, antiper -
spirants, and various dyes. 147–149 Additionally, DMSO has been mixed with skin anti -
septics such as hexachlorophene, the anthelmintic thiabendazole, and both estrogens and corticoids, which, when applied topically in DMSO, exerted their characteristic biologic effect in immature female rats. 150,151
There are thousands of compounds used in pharmacology research that have been 
reported to be solubilized in varying concentrations of DMSO. Balakin et al.152 have 
compiled a comprehensive reference database of proprietary data on compound solu -
bility and shown that, as of 2004, 55,277 organic compounds possess good DMSO solubility and 10,223 organic compounds possess poor DMSO solubility. One caveat when using DMSO as a solvent in testing the activity of a drug as a 
potential treatment is the singular action exerted by DMSO, which, in some cases, may show more activity than the drug being tested. 76 This error, of course, can be 
easily avoided by testing DMSO alone as a control during the testing procedure, but it does not avoid the error that the inclusion of DMSO in the drug preparation may synergistically enhance and improve the experimental drug’s effect by increasing its penetration into the lesion site or by prolonging its kinetic distribution. VETERINARY USES
DMSO has been approved for two veterinary products in the United States. Domoso (90% DMSO) is indicated for acute swelling in dogs and horses, which can be applied as a gel or liquid preparation. Synotic is 60% DMSO and 0.01% fluocinolone acetonide, indicated for the relief of pruritus and inflammation associated with acute and chronic otitis in the dog or horse. The majority of veterinary reports published on the use of DMSO in animals concern horses and dogs. Many of the injuries seen in horses have been successfully treated with DMSO 
especially when edema and inflammation are involved in the lower extremities. Some conditions amenable to DMSO treatment include tendonitis, periosteal involvement of metacarpal bones, osteoarthritis, bursitis, open wound infections, and traumatic injuries involving tissue swelling and hemorrhage. The usual treatment dose for these 
equine conditions is 1 g/kg body weight intravenously of DMSO in a 40% solution 
with a maximum duration of treatment of 5 days. 153
DMSO has been used for open wounds in horses where it appeared to stimu -
late healthy granulation of the wound within the first few days.154 The granulation 38 Dimethyl Sulfoxide (DMSO) in Trauma and Disease
tissue after a 2-week course of DMSO three times/day was reduced to normal within 
30 days.154
Endotoxemia is a severe and ubiquitous disease in horses receiving IV lipopoly -
saccharide. IV DMSO at 1 g/kg body weight improved the effect of lipopolysaccha -
ride on fever.155
In a double-blinded, crossover, paired study with a 1-week washout period, mid-
carpal joints in horses with acute inflammation were topically treated with DMSO gel 15 g at 90%, which was seen to penetrate in the synovial fluid by the use of gas chromatography in sufficient quantities to decrease joint inflammation. 156
Fungal infection in the eyes of horses has been treated with DMSO in combination 
with antifungal agents. Horses with keratomycoses were given DMSO–  i traconazole 
0.25 mL of a 1% itraconazole with 30% DMSO in a petrolatum-based ointment every 4 h for 16–53 days, and it was seen that 8 of 10 eyes treated with this mixture resolved completely. 157
DMSO has been used in small animal practice mostly involving dogs. The con -
ditions that are reported to be helped by DMSO include traumatic edema, sprains, tendonitis, intervertebral disk disease, mastitis, and soft tissue inflammatory problems. 158
Uveitis was induced in dogs by intracameral injection of canine lens protein, 
and after DMSO application, intraocular pressure and fibrin production were decreased after treatment possibly from the antagonism of DMSO to lipoxygenase formation. 159
One interesting report concerns the anecdotal use of DMSO for 2 years in a 
dog diagnosed with hypoalbuminemia, proteinuria, and renal amyloidosis. Two years after the initiation of DMSO treatment, the 24 h urinary protein excretion returned to normal, while serum albumin concentrations increased to within nor -
mal range. 160 These findings would need to be replicated in a larger study but may 
serve as a clue of the ability of DMSO to act as a chemical chaperone in protracted disorders such as renal amyloidosis, a progressive and fatal disease that is difficult to treat or cure. TERATOLOGY AND LD50
The intraperitoneal administration of 5.5 g/kg of DMSO as a single dose to pregnant hamsters induced developmental malformations of their embryos. 161
Both DMSO and diethyl sulfoxide are teratogenic when injected into the chick 
embryo, the classification of malformations being dependent upon the stage of embryonic development at the time of treatment. The same drugs when adminis -
tered by various techniques to mice, rats, and rabbits in which fertility had been established did not cause any embryonic malformations. 162
Teratogenic effects produced in laboratory animals were not observed when ther -
apeutic doses of DMSO were used, and LD50 could be reached only by going far 
beyond the therapeutic doses.162 The LD50 of DMSO in animals varies depending on 
the species and the route of administration (Table 2.2). However, the toxicity of DMSO in pregnant or lactating women has not been 
determined and is consequently not recommended in his population group.39 DMSO in Basic Pharmacology
OCULAR EFFECTS
Following high oral or topical administration of DMSO, certain eye changes in the 
dog have been reported.163 The lens changes were first observed in dogs receiving 5 g 
DMSO/kg after 9 weeks of administration.163 At lower dose levels, the change was 
observed later. The lens alteration consisted mainly of a change in the refractive index of the lens. 163 The lens changes were characterized by a decrease in the normal relucency of 
the lens cortex, causing the normal central zone of the lens to act as a biconvex lens. The functional effect of this refractive change would be a tendency toward myopia. 163
In swine, dermal application of 4.5 g 90% DMSO/kg twice daily caused similar 
lens changes by 90 days of treatment. The eye changes were slowly reversible after DMSO was discontinued but with a definite species difference, the dog being the slowest to exhibit improvement. 164
Ocular effects in dogs started after 5–10 weeks of dosing of DMSO at 9 mL/kg 
and involved nuclear lens changes with changes of the refractive index plus transi -
tory equatorial opacities during the fifth month and changes in the vitreous humor.165 
Similar changes were observed when DMSO was given more slowly at 3 mL/kg, with alterations to the vitreous being first seen after 9–10 months at this dose level. Progressive refractive index changes occurred when DMSO was given for 6 months at 1 mL/kg but none of the treated animals showed nuclear lens opacity. When DMSO dosing was stopped, refractive nuclear changes were no longer seen. 165
Daily IV doses of 3 g/kg DMSO in a 40% solution given to rhesus monkeys 
for nine consecutive days did not lead to any lens changes.166 The monkeys were 
monitored before and after treatment for 4 months for changes in blood chemistry, hematology, urine, ocular, neurological, and cardiovascular systems. No significant or long-lasting changes were recorded in any of the parameters studied when these TABLE 2.2
LD50 for Various Animal Species in g/kg Using 
Different Routes of Administration
LD50 of DMSO in Animals
Species Route of Administration g/kg
Mouse SQ 13.9–20.5
Mouse IV 3.8–10.7
Mouse PO 15–22
Mouse IP 20.0
Rat IV 5.2–5.3
Rat PO 16.0–28.3
Rat IP 6.5–13.6
Dog IV 2.5
Guinea pig IP 6.5
Chicken PO 12.5
Note:  SQ, subcutaneous; IV , intravenous; PO, oral; IP, intraperitoneal.40 Dimethyl Sulfoxide (DMSO) in Trauma and Disease
data were compared to monkeys receiving IV daily physiological saline solution.166 
These negative findings of lens changes were confirmed in monkeys receiving 
11 g/kg oral DMSO/day for 1 year.167 The unique lens changes reported in some 
animal species have not been reported in 213 human volunteers receiving 1 g/kg of 80% DMSO applied dermally per day for 14 days and followed up for 90 days. 167
INTRAWOUND ADMINISTRATION OF DMSO
Managing pain is very important as we have reviewed earlier, but even more so when pain is due to tissue wounds. Tissue wounds can lead to infection, tissue scar -
ring, and tightening of the skin, which can make joint mobility difficult and painful. These effects can often be minimized with good pain control medication. Thus, pain needs to be treated as soon as possible to avoid further tissue damage. Most of the pain medications for penetrating wounds of the skin have a systemic 
effect, and few are effective when given locally. DMSO has never been used follow -
ing direct intrawound administration. The advantages of intrawound administration are that a local rather than systemic effect on pain can be achieved, thus reducing side effects of the medication. One study has reported that damage to the plantar surface of a hind paw in rats 
received intrawound administration of DMSO. 168 Before the closure of the wound, 
DMSO was administered using a sterile pipette at the minimal dose of 10 μL in a 
100% solution and applied deep into the damaged plantar tissue. The application of intrawound DMSO administration resulted in significant control of pain when a thermal hyperalgesia stimulus was applied to the affected paws of the treated rats but not to control rats receiving a placebo. The authors concluded that DMSO appeared effective in the treatment of acute pain and should be further tested in tissue injuries resulting in wound damage and burns. 168
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Epub ahead of print.49
3DMSO Clinical 
Pharmacology
DMSO IN DISEASE
Although dimethyl sulfoxide (DMSO) was first synthesized by the Russian  s cientist 
Alexander Zaytsev in 1866, it took another century for its pharmacotherapeutic 
properties to be discovered by Jacob et  al.,1 beginning in 1964. Discovering the 
pharmacotherapeutic activities of DMSO is a lesson in how good science works, involving a keen observation, the hypothesis that was formulated, testing, and the conclusion. Stanley Jacob, a surgeon and, at the time, the head of the Organ Transplant 
Program at Oregon Health Sciences University, had observed that besides the cryo -
protective properties exhibited by DMSO in the preservation of frozen organs, its topical application seemed to quickly penetrate the skin without damaging it, result -
ing in a garlicky taste in the mouth within seconds after its application. Intrigued by this suspected cause-and-effect reaction, Jacob and his colleagues
1 began a research 
journey to find out what else this simple molecule could do and, in so doing, set off an explosion of publications worldwide that would culminate in more than 45,000 scientific articles, which continue growing to this day. The use of DMSO as a pharmacotherapeutic agent for clinical maladies dis-
cussed in this chapter has, in some cases, not been clinically exploited to its full extent despite consistent evidence of its safety and efficacy in a host of medical conditions. It is hoped that this review can aid the reader to better understand the unusual properties of this simple molecule and help dispel both unfounded negative notions and positive expectations that have emerged during the history of DMSO and which are either anecdotal in content or unsupported by scientific evidence. Some of the useful features that characterize DMSO use are as follows:
 1 . I t can be administered intravenously, orally, topically, or intravesically.2,3
 2 . W hen combined with other selected compounds, it can enhance their  t issue 
penetration, enhance their pharmacological activity synergistically, and reduce their toxicity by lowering their dose. 4
 3 . I t is relatively nontoxic at a wide range of concentrations and routes of 
administration.550 Dimethyl Sulfoxide (DMSO) in Trauma and Disease
PAIN
Pain is essentially an unpleasant perceptual process that arises in response to inflamed 
or injured tissues.6 Pain can be perceived from endogenous stressors, including dam -
age and/or inflammation within both neuronal and non neuronal tissues, or by exoge -
nous stress that can be produced by psychosocial factors. Physical pain sensation and suffering can be measured, though not always in a precise manner, to provide useful parameters for clinical assessment. Dangerous tissue-damaging pain often develops from skeletal muscle and from joints and less often from viscera and almost never from liver or lung even when these organs are severely damaged or diseased. 7 The 
likely explanation for this curious absence of pain sensation in those organs is that they lack a network of sensory nerves for the transmission of nociceptive signals to the brain. 8 Similarly, viscera, such as gut and urinary tract, can elicit pain following 
ischemic tissue damage or inflammation (e.g., Crohn’s disease or cystitis), but this type of pain is not as common as musculoskeletal or joint pain. 9
Peripheral nerve stimulation in humans has shown the involvement of two afferent 
fiber groups subserving pain.10 Due to their higher conduction velocity, fine myelin -
ated fibers of the A- δ (gamma) pain group when activated evoke quick, shallow pain 
interpreted as sharp or pricking,11 whereas activity in slow nonmyelinated C-fibers 
responds to stimuli that have stronger intensities and account for the slow, but deeper and widespread pain over an unspecific area, often characterized as a burning sensa -
tion. 12 In response to single shocks, the A- δ pain is more severe than C-fiber pain. But C-fiber pain is more severe when the stimulation is repetitive, which is the basis of chronic pain. 13 Strong C-fiber pain is thought to underlie the suffering felt in neu -
ropathic pain14,15 (see Chapter 2). Due to the high subjectivity involved in pain sensation in humans, the assessment 
of pain medications and even nonpharmacological interventions can be difficult to measure with respect to effectiveness of easing pain sensation since the perception of pain can change over time and even during the course of a day. 16
For example, chronic neuropathic pain has a complex pathophysiology and is dif -
ficult to treat.17 The clinical measures that evaluate pain alleviation involve patient-
reported outcomes where the patient is the most important evaluator of the analgesic being tested. 18 This can present a major problem involving bias for the clinician and 
the patient as well as to regulatory agencies that must sift through the merit of such evidence before approving a prescriptive analgesic for the market, a market whose revenue classifies it as a billion-dollar industry. The second problem related to pain medications in clinical studies’ assessments 
is that analgesics are unusually assessed by a single pain rating. 19 This approach has 
yielded conflicting and confusing results that put into question the true pharmaco -
logical action of an analgesic with that of a placebo effect or nocebo effect. The pla -
cebo effect describes the improvement seen when patients, unknowingly, are given a sham or inactive ingredient as a pain-relieving treatment that the patients believe 
will alleviate their pain, as it often does. 20 This is a very real physiological effect that 
remains a scientific mystery but nevertheless a valid response. The nocebo effect is 
the opposite: patients believe that even a potent analgesic will make their pain feel worse, and often it does. 2151 DMSO Clinical Pharmacology
Due to this lack of scientific objectivity in measuring analgesic properties of effi -
cacy, information derived from the impact of treatments on (1) the quality of pain 
symptoms, (2) improved anatomic or physiological functioning, and (3) overall well-being of the patient can add to the validity and confidence that a particular analgesic for a particular pain complaint shows evidence or not that it is a useful pain reliever. We will call the criteria of using these three guidelines to measure analgesic efficacy, the QFW values , for quality of easing pain (Q), restoring or significantly improv -
ing anatomic–physiological function (F), and general well-being (W) subjectively expressed by the patient following treatment. Thus, two subjective and one objective values complementary to each other to 
assess the effectiveness of DMSO on pain add a level of accuracy and confidence into what was previously considered a purely subjective assessment of a drug’s action to alleviate pain. Oral nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2-
selective (COX-2) inhibitors are frequently recommended for the management of osteoarthritis pain. However, serious gastrointestinal and cardiovascular systemic adverse events are associated with oral NSAIDs and COX-2 inhibitors, thus limiting their usefulness. For these reasons, many clinicians treating patients with an assortment of painful 
disorders turned to other possible remedies with a better safety margin. Because pain is a primitive and conspicuously unpleasant sensation, it is gener -
ally regarded as a warning signal of danger. This unpleasant or aversive sensation originates from some specific region of the body. Since pain is highly subjective in nature, it is often difficult to treat clinically despite the fact that it is the most com -
mon complaint that patients describe when seeking medical help. Specific pain sen -
sations have been described as burning, pricking, stinging, aching, and soreness. 11
When the clinical potential of DMSO was first discovered,1 its topical application 
for the relief of musculoskeletal pain was consistently shown. DMSO and aspirin work similarly by blocking the production of certain prosta -
glandins by controlling the on–off switch in cells that regulate pain and inflammation, among other things. That is likely the reason why aspirin stops mild inflammation and pain. However, DMSO goes a step farther than aspirin in that it not only blocks the prostaglandins that can induce pain and inflammation, such as prostaglandin E
2 
(PGE2),22 but also stops or slows down conduction of pain fibers when it is adminis -
tered topically or internally.23 PGE2 is of particular interest because it is involved in all 
processes leading to the classic signs of inflammation: redness, swelling, and pain.24 
Also, unlike aspirin, DMSO is not considered toxic to the stomach or gut where aspi -
rin can cause peptic ulcers or gastrointestinal tract irritation at therapeutic doses.25
DMSO has been found to block conduction of C-fibers when applied directly to 
a sensory nerve, even in low concentrations (5%–7% v/v).23 Higher concentrations 
 completely blocked C-fiber conduction, with a minimum blocking concentration of 
9%.23 When the application of DMSO continues on a nerve, besides blocking large 
C-fibers, it also blocks small pain fibers, such as A- δ (delta) and sensory receptors, such 
as those associated with noxious stimuli response.26 This action makes the repeated 
application of DMSO often show dramatic effects on musculoskeletal pain disorders 4–7 days after the initial application showed little to no response. 2752 Dimethyl Sulfoxide (DMSO) in Trauma and Disease
One early study in the use of DMSO for musculoskeletal pain was on six patients 
presenting with acute calcified supraspinatus bursitis, a painful condition due to 
deposition of calcium hydroxyapatite within tendons, usually of the rotator cuff.28 
All six patients had been refractory to conventional treatments whose duration of pain had varied from 2 days to 4 weeks. Following one or several topical DMSO applications at a concentration of 70%, dramatic symptomatic relief occurred in all six patients. 28 This relief consisted in pain alleviation, improvement in the range of 
motion and mobility of the affected joint, and patient satisfaction of the treatment results indicated a significant reduction in disability. 28
Using the QFW values discussed earlier as the assessing criteria for the effec -
tiveness of DMSO, there is confidence in the conclusion that DMSO treatment improved the quality of symptoms, anatomic functioning of extremities and joints with increased mobility, and overall well-being of the patient. Local skin irritation and a characteristic clam-like  odor to the breath were the only side effects observed 
in the study by Lockie and Norcross
28. In that early study by Lockie and Norcross,28 
over 100 patients were treated with topical DMSO generally with similar results as those treated with calcified supraspinatus bursitis for such conditions as degenera -
tive arthritis, rheumatoid arthritis, periarthritis of varying degrees of acuteness and severity, and various musculoskeletal complaints following muscle trauma sustained by professional football players. 28 In that study, it was observed that patients unable 
to tolerate 70% DMSO, a 10% addition of glycerin avoided or lessened the skin irri -
tation when it occurred.28 The Lockie and Norcross28 study became the gold standard 
for evaluating DMSO in other musculoskeletal and joint pain resulting in limited mobility of body extremities. Several additional early studies on the activity of DMSO in musculoskeletal pain 
disorders were reported. Blumenthal and Fuchs
29 reported on 122 patients ranging in 
age from 17 to 89 years with musculoskeletal sprains or injuries to the chest, back, pelvis, and extremities, who were treated for several days or months with topical DMSO using undisclosed doses. These authors reported that 74% of patients given DMSO showed excellent–good response to treatment especially if the pain was acute rather than chronic, while 24% of the patients showed no improvement of symp -
toms. 29 This study failed to provide QFC values and other important information 
involving treatment times, doses, and manner of assessment and can therefore be considered more anecdotal in nature. DMSO has been used in gel form instead of an aqueous solution for lateral epi -
condylitis (tennis elbow) and humero-scapular pain. In a placebo-controlled double-blind study, 157 patients received either 10% DMSO gel applied three times per day for 2 weeks or the inactive gel excipient. 30 Treatment was started within 72 h after the 
acute onset of symptoms and pain, and mobility of the joints was observed after 3, 7, and 14 days of treatment with DMSO as compared to the placebo gel recipients. Mild undesired events were seen in 8 of 77 DMSO patients and 3 of 80 patients treated with the placebo gel. 30
One of the first studies to investigate the analgesic potential of DMSO in rheuma -
toid arthritis, osteoarthritis, tenosynovitis, and other articular disorders came from Japan in 1967. 31 These investigators reported using 50% aqueous solution of DMSO 
topically for 3 days on 318 patients and reported DMSO significantly relieved joint 53 DMSO Clinical Pharmacology
pain when assessed 14 days later, using a variety of tests involving articular symp -
toms and signs, such as spontaneous pain, tenderness on pressure, pain on motion, 
local heat, grip strength, circumference of joint, and range of joint motion.31 They 
concluded that DMSO improved grip strength, relieved pain, and increased the range of joint motion but had no effect on joint swelling as compared to placebo. DMSO seemed more effective in cases of short duration. The only unfavorable side effect was temporary local irritation of the skin, which disappeared after the last DMSO application. 31
As reports of the analgesic action of topical DMSO in arthritis and musculoskel -
etal disorders became known, other investigators looked into the possibility of using topical DMSO for surface tissue damage. One of these reports examined incisional pain after thoracotomy. 32 DMSO (60% concentrations) was applied directly to the 
closed wound incision extending 10 in. on either side. The skin was then permitted to dry for 10 min, and a sterile dressing was applied. Six hours later, the dressing was removed, and the same DMSO amount and concentration were reapplied. The applications were repeated every 6 h for 3 days. Thereafter, from 4 to 6 days, 70% DMSO was applied to the healing wound, and the treated patients as a group were able to move about more easily both in and out of bed, to resume early motion in the arm and shoulder in the operative side, and, in general, to enjoy a more rapid and less complicated postoperative course than patients who had not been treated with DMSO. 32 Also, it was observed that treated patients showed fewer gastrointestinal 
complications, such as nausea, vomiting, ileus, and constipation. The investigators, surgeons, and nurses providing the daily DMSO treatments were impressed with the apparent effectiveness of DMSO in relieving the usual postoperative thoracotomy pain. 32
Patients with painful furuncular otitis were treated with 90% topical DMSO 
by applying DMSO into the auditory meatus and to the adjacent outer ear using a dripping-wet cotton-tipped applicator. 33 Patients were treated once daily or twice 
daily in serious cases.
Dimethyl_Sulfoxide_(DMSO)_in_Trauma_and_Disease_[2015].txt
Summarize the following text section accurately and concisely. Maintain specific details and numerical information, and use anti-repetition mechanisms:

        ARDS is char -
acterized by interstitial edema, low paO
2, rising paCO2, and complete opacification TABLE 2. 1
Survival Rates of Hypoxemic Rats Exposed to 3 min of Pure Nitrogen in 
a Closed Chamber Pretreated with DMSO, Doxapram, and Ethamivan
Effects of DMSO on Experimental Hypoxemia in Rats
Agent Survivors/Total Survival, % P Value
DMSO 18/20 90 <0. 0025
Saline 3/20 15
Doxapram 18/20 90 <0. 0025
Saline 2/20 10
Ethamivan 6/20 30 >0. 4
Saline 3/20 15
Note:  See te xt for details. 34 Dimethyl Sulfoxide (DMSO) in Trauma and Disease
of both lung fields on chest x-ray. A 10% DMSO solution was given intravenously to 
three patients nearing death presenting with ARDS who were refractory to classical therapy. All three patients showed marked improvement 1  h after the application of DMSO with respect to oxygen saturation, increased paO
2, and lowered paCO2. One patient showed a dramatic improvement of the chest x-ray, which resolved over a period of 1 week. It was concluded by the author of the study that DMSO use in ARDS merits further investigation. 130
A model of ARDS using formylated tripeptide formyl-norleucyl-leucyl-  
phenylalanine (FNLP) was instilled intratracheally into hamsters to induce acute edematous lung injury. Intratracheal FNLP is time dependent and dose dependent and increases neutrophils to create neutrophil alveolitis and leak of intravenously injected albumin into the extravascular lung space (lung leak). 131
It was observed that treatment with 0. 20% DMSO significantly decreased neutro -
phil alveolitis and lung leak in hamsters following FNLP intratracheally, possibly by inhibiting neutrophil chemotaxis. 131
DMSO is reported to increase hypoxic tolerance of brain slices under hypoxic  or 
ischemic  conditions. After the induction of hypoxia or ischemia in the CA1 region 
of hippocampal slices of adult guinea pigs, evoked potentials recording showed that during superfusion with artificial CSF containing DMSO 14. 1 mmol/L the latency of anoxic terminal negativity was markedly improved when compared to the control brain slices, demonstrating a neuroprotective effect of DMSO on ischemia/hypoxia. 132
EXPERIMENTAL BLUNT CHEST TRAUMA
Blunt chest trauma is an injury to the chest caused by an impact from a blunt object. Blunt chest trauma puts multiple adjoining structures at risk of injury. This type of injury can involve cardiac contusion, cardiovascular injury, and pulmonary lacera -
tions. Traffic accidents are the most frequent cause of blunt chest trauma and cardiac contusions due to acceleration–deceleration and usually involving a direct blow to the chest. Many other causes can result in blunt chest trauma, including a violent fall, explosion, aggression, and various types of high-risk sports. The majority of blunt chest injuries can be classified into three types: minor chest 
wall injuries, major but stable chest wall injuries, and flail chest injuries. The first two chest injuries can involve fracture of the bony chest wall or no fracture. Flail chest is a life-threatening medical condition where the rib cage breaks under extreme stress, damaging ribs in multiple places where they become detached from the rest of the chest wall moving independently of the rib cage. To study traumatic pulmonary contusion, DMSO was compared to the powerful anti-
inflammatory agent dexamethasone using a designed thoracic trauma model in rats. 132a 
DMSO (1. 2 g/kg) and dexamethasone (10 mg/kg) were given intraperitoneally 15 min prior to injury. The effects of blunt trauma to lung tissue was examined biochemically and histopathologically. A number of pathologic signs were observed in all animal 
groups following blunt trauma, including alveolar edema, congestion, and pulmonary 
parenchymal hemorrhage. 132a
The levels of oxidative stress predictors malondialdehyde and nitric oxide were 
lower with both dexamethasone- or DMSO-treated animals when compared with 35 DMSO in Basic Pharmacology
untreated blunt chest trauma animals. This finding indicated the well-known antioxi -
dant properties of DMSO and dexamethasone in inflammatory conditions. However, 
further analysis revealed that only DMSO-treated animals prevented further injury by decreasing neutrophil infiltration and endothelial cell injury of blood vessels near the injury site following the lung contusion. 132a
As we have reviewed in Chapter 8, the production of excessive free radicals and 
the release of local inflammatory mediators including cytokines such as interleu -
kin 6, tumor necrosis factor- α, and nitric oxide are generally the culprits responsible 
for the deadly pathologic cascades seen following traumatic brain injury. DMSO is a powerful free radical scavenger and effective anti-inflammatory agent that is able to quell the cytokine storm  seen after the blunt chest trauma. In addition, 
these cytokines can lead to complications affecting immunosuppression, leading to multi organ damage. 72
AUTOPHAGY
Autophagy is a dynamic process of subcellular component degradation, which has sparked a great deal of interest in the last decade since it is now recognized to be involved in various developmental processes affecting certain disorders, including neurodegeneration and cancer. 133
Autophagy is a basic catabolic mechanism in eukaryotes that involves cell deg -
radation of unnecessary or dysfunctional cellular components in the cytoplasm and sequesters these into double-membrane vesicles where they are delivered to the lyso -
some/vacuole for breakdown and eventual recycling. 134 The breakdown of cellular 
components can ensure cellular survival during nutrient starvation by maintaining cellular energy levels. 134 Normally, when autophagy is regulated, synthesis, degrada -
tion, and recycling of these cellular components are maintained. Targeted cytoplas -
mic components are isolated from the rest of the cell within the autophagosomes, which are then fused with lysosomes and degraded or recycled. The relevance of autophagy in disease is seen as an adaptive response to survival, but in certain cir -
cumstances, autophagy has also been described as a promoter of cell death and morbidity. 134
Three different forms of autophagy have been described. These are macroau -
tophagy, microautophagy, and chaperone-mediated autophagy (CMA). 135
Autophagy can function as a cytoprotective mechanism, but it also has the 
capacity to cause cell death. Autophagy is a major mechanism for degrading long-lived cytosolic proteins and the only known pathway for degrading organelles. 136 
Autophagy is activated by many forms of stress, including nutrient and energy starvation, oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, and infections. Autophagy recycles amino acids and fatty acids to produce energy while removing damaged cell components, thereby playing an essential role in cell survival and intracellular surveillance mechanism, which is indispens -
able for maintaining cell health. When this process is abnormal, autophagy leads to cell death. 137
CMA is a selective type of autophagy by which specific cytosolic proteins are 
sent to lysosomes for degradation. 36 Dimethyl Sulfoxide (DMSO) in Trauma and Disease
The chemical chaperones in the cytosol normally unfold substrate proteins prior 
to their translocation across the lysosomal membrane, but when this process is aber -
rant, DMSO administration, acting a chemical chaperone, may induce CMA and 
exert a protective effect toward the cell’s survival (see also Chapter 1, “DMSO as a Chemical Chaperone”). For example, DMSO appears to have a beneficial role in inducing autophagy as 
a chemical chaperone by reducing free fatty acid–induced hepatic fat accumulation in a dose-dependent manner. 138 Treatment with 0. 01% DMSO for 16 h significantly 
reduced palmitate-induced triglyceride accumulation in rat hepatocytes. 138 This 
effect by DMSO was postulated to result from the downregulation of the ATF4/AKT1 pathway, a stress-induced transcription factor that is overexpressed in many cancers and is an important mediator of the unfolded protein response. 138,139
DIURESIS
DMSO is a powerful diuretic when used intravenously. A fivefold increase in urine excretion as compared to saline controls is seen after 1 h of 40% DMSO IV given at 2. 5 g/kg in dogs with spinal cord trauma. 127 In rats, DMSO given topically five times 
daily increased urine volume 10-fold. 140 The brisk diuretic response to 40% DMSO 
infusion has been seen in patients treated for high intracranial pressure secondary to head injury. 141 Diuresis after high doses of DMSO is accompanied by electro -
lyte changes involving sodium and potassium excretion,142 but these changes can be 
minimized by reducing excessive DMSO fluid overload and by carefully monitoring electrolytes after high and repeated dosing with DMSO. 143
These collective findings suggest that DMSO merits clinical evaluation as a 
potent and primary treatment when diuresis is indicated in water retention for such conditions as cirrhosis, acute or chronic renal failure, nephrotic syndrome, and con -
gestive heart failure. CHOLINESTERASE INHIBITION
DMSO is reported to inhibit the isolated and innervated guinea pig atrium following incubation in a bath mimicking the action of neostigmine by lowering the vagal thresh -
old to electrical stimulation. 144 It was found that this action by DMSO at doses of 0. 01–1. 0 
mol/L incubated for 30 min  in the guinea pig atrium bath was able to inhibit erythro -
cyte cholinesterase, the enzyme that breaks down the neurotransmitter acetylcholine. 144
The cholinesterase inhibitory activity by DMSO could reasonably target the low -
ering of high blood pressure, bronchoconstriction, and intraocular pressure. Despite their annoying gastrointestinal effects, cholinesterase inhibitors are also used in treat -
ing the symptoms of Alzheimer’s disease,
138 a disorder where DMSO dose adjustment 
could avoid the gastrointestinal side effects seen with stronger cholinesterase drugs. This aspect of DMSO therapy will be more fully discussed in Chapter 8. DMSO was studied at the neuromuscular junction of the frog cutaneous pectoris 
using electrophysiological techniques and found to elevate the amplitude of extra -
cellularly recorded miniature end-plate potentials as well as the time constant of their monoexponential decay. These findings indicated that DMSO partially blocked 37 DMSO in Basic Pharmacology
cholinesterase activity and the presynaptic action of acetylcholine release,145 an 
action that has been confirmed on a variety of invertebrate muscles. 146
SOLVENT ACTION
DMSO is a solvent for many aromatic and unsaturated hydrocarbons as well as inor -
ganic salts and nitrogen-containing compounds. This ability to act as a universal 
solvent may be due to DMSO’s high dielectric constant due to the polarity of the sulfur–oxygen bond. DMSO has been shown to carry physostigmine and phenylbutazone through the 
skin of the rat. Moreover, there  is evidence that DMSO enhances the percutaneous 
absorption of many other compounds, including steroids, vasoconstrictors, antiper -
spirants, and various dyes. 147–149 Additionally, DMSO has been mixed with skin anti -
septics such as hexachlorophene, the anthelmintic thiabendazole, and both estrogens and corticoids, which, when applied topically in DMSO, exerted their characteristic biologic effect in immature female rats. 150,151
There are thousands of compounds used in pharmacology research that have been 
reported to be solubilized in varying concentrations of DMSO. Balakin et al. 152 have 
compiled a comprehensive reference database of proprietary data on compound solu -
bility and shown that, as of 2004, 55,277 organic compounds possess good DMSO solubility and 10,223 organic compounds possess poor DMSO solubility. One caveat when using DMSO as a solvent in testing the activity of a drug as a 
potential treatment is the singular action exerted by DMSO, which, in some cases, may show more activity than the drug being tested. 76 This error, of course, can be 
easily avoided by testing DMSO alone as a control during the testing procedure, but it does not avoid the error that the inclusion of DMSO in the drug preparation may synergistically enhance and improve the experimental drug’s effect by increasing its penetration into the lesion site or by prolonging its kinetic distribution. VETERINARY USES
DMSO has been approved for two veterinary products in the United States. Domoso (90% DMSO) is indicated for acute swelling in dogs and horses, which can be applied as a gel or liquid preparation. Synotic is 60% DMSO and 0. 01% fluocinolone acetonide, indicated for the relief of pruritus and inflammation associated with acute and chronic otitis in the dog or horse. The majority of veterinary reports published on the use of DMSO in animals concern horses and dogs. Many of the injuries seen in horses have been successfully treated with DMSO 
especially when edema and inflammation are involved in the lower extremities. Some conditions amenable to DMSO treatment include tendonitis, periosteal involvement of metacarpal bones, osteoarthritis, bursitis, open wound infections, and traumatic injuries involving tissue swelling and hemorrhage. The usual treatment dose for these 
equine conditions is 1 g/kg body weight intravenously of DMSO in a 40% solution 
with a maximum duration of treatment of 5 days. 153
DMSO has been used for open wounds in horses where it appeared to stimu -
late healthy granulation of the wound within the first few days. 154 The granulation 38 Dimethyl Sulfoxide (DMSO) in Trauma and Disease
tissue after a 2-week course of DMSO three times/day was reduced to normal within 
30 days. 154
Endotoxemia is a severe and ubiquitous disease in horses receiving IV lipopoly -
saccharide. IV DMSO at 1 g/kg body weight improved the effect of lipopolysaccha -
ride on fever. 155
In a double-blinded, crossover, paired study with a 1-week washout period, mid-
carpal joints in horses with acute inflammation were topically treated with DMSO gel 15 g at 90%, which was seen to penetrate in the synovial fluid by the use of gas chromatography in sufficient quantities to decrease joint inflammation. 156
Fungal infection in the eyes of horses has been treated with DMSO in combination 
with antifungal agents. Horses with keratomycoses were given DMSO–  i traconazole 
0. 25 mL of a 1% itraconazole with 30% DMSO in a petrolatum-based ointment every 4 h for 16–53 days, and it was seen that 8 of 10 eyes treated with this mixture resolved completely. 157
DMSO has been used in small animal practice mostly involving dogs. The con -
ditions that are reported to be helped by DMSO include traumatic edema, sprains, tendonitis, intervertebral disk disease, mastitis, and soft tissue inflammatory problems. 158
Uveitis was induced in dogs by intracameral injection of canine lens protein, 
and after DMSO application, intraocular pressure and fibrin production were decreased after treatment possibly from the antagonism of DMSO to lipoxygenase formation. 159
One interesting report concerns the anecdotal use of DMSO for 2 years in a 
dog diagnosed with hypoalbuminemia, proteinuria, and renal amyloidosis. Two years after the initiation of DMSO treatment, the 24 h urinary protein excretion returned to normal, while serum albumin concentrations increased to within nor -
mal range. 160 These findings would need to be replicated in a larger study but may 
serve as a clue of the ability of DMSO to act as a chemical chaperone in protracted disorders such as renal amyloidosis, a progressive and fatal disease that is difficult to treat or cure. TERATOLOGY AND LD50
The intraperitoneal administration of 5. 5 g/kg of DMSO as a single dose to pregnant hamsters induced developmental malformations of their embryos. 161
Both DMSO and diethyl sulfoxide are teratogenic when injected into the chick 
embryo, the classification of malformations being dependent upon the stage of embryonic development at the time of treatment. The same drugs when adminis -
tered by various techniques to mice, rats, and rabbits in which fertility had been established did not cause any embryonic malformations. 162
Teratogenic effects produced in laboratory animals were not observed when ther -
apeutic doses of DMSO were used, and LD50 could be reached only by going far 
beyond the therapeutic doses. 162 The LD50 of DMSO in animals varies depending on 
the species and the route of administration (Table 2. 2). However, the toxicity of DMSO in pregnant or lactating women has not been 
determined and is consequently not recommended in his population group. 39 DMSO in Basic Pharmacology
OCULAR EFFECTS
Following high oral or topical administration of DMSO, certain eye changes in the 
dog have been reported. 163 The lens changes were first observed in dogs receiving 5 g 
DMSO/kg after 9 weeks of administration. 163 At lower dose levels, the change was 
observed later. The lens alteration consisted mainly of a change in the refractive index of the lens. 163 The lens changes were characterized by a decrease in the normal relucency of 
the lens cortex, causing the normal central zone of the lens to act as a biconvex lens. The functional effect of this refractive change would be a tendency toward myopia. 163
In swine, dermal application of 4. 5 g 90% DMSO/kg twice daily caused similar 
lens changes by 90 days of treatment. The eye changes were slowly reversible after DMSO was discontinued but with a definite species difference, the dog being the slowest to exhibit improvement. 164
Ocular effects in dogs started after 5–10 weeks of dosing of DMSO at 9 mL/kg 
and involved nuclear lens changes with changes of the refractive index plus transi -
tory equatorial opacities during the fifth month and changes in the vitreous humor. 165 
Similar changes were observed when DMSO was given more slowly at 3 mL/kg, with alterations to the vitreous being first seen after 9–10 months at this dose level. Progressive refractive index changes occurred when DMSO was given for 6 months at 1 mL/kg but none of the treated animals showed nuclear lens opacity. When DMSO dosing was stopped, refractive nuclear changes were no longer seen. 165
Daily IV doses of 3 g/kg DMSO in a 40% solution given to rhesus monkeys 
for nine consecutive days did not lead to any lens changes. 166 The monkeys were 
monitored before and after treatment for 4 months for changes in blood chemistry, hematology, urine, ocular, neurological, and cardiovascular systems. No significant or long-lasting changes were recorded in any of the parameters studied when these TABLE 2. 2
LD50 for Various Animal Species in g/kg Using 
Different Routes of Administration
LD50 of DMSO in Animals
Species Route of Administration g/kg
Mouse SQ 13. 9–20. 5
Mouse IV 3. 8–10. 7
Mouse PO 15–22
Mouse IP 20. 0
Rat IV 5. 2–5. 3
Rat PO 16. 0–28. 3
Rat IP 6. 5–13. 6
Dog IV 2. 5
Guinea pig IP 6. 5
Chicken PO 12. 5
Note:  SQ, subcutaneous; IV, intravenous; PO, oral; IP, intraperitoneal. 40 Dimethyl Sulfoxide (DMSO) in Trauma and Disease
data were compared to monkeys receiving IV daily physiological saline solution. 166 
These negative findings of lens changes were confirmed in monkeys receiving 
11 g/kg oral DMSO/day for 1 year. 167 The unique lens changes reported in some 
animal species have not been reported in 213 human volunteers receiving 1 g/kg of 80% DMSO applied dermally per day for 14 days and followed up for 90 days. 167
INTRAWOUND ADMINISTRATION OF DMSO
Managing pain is very important as we have reviewed earlier, but even more so when pain is due to tissue wounds. Tissue wounds can lead to infection, tissue scar -
ring, and tightening of the skin, which can make joint mobility difficult and painful. These effects can often be minimized with good pain control medication. Thus, pain needs to be treated as soon as possible to avoid further tissue damage. Most of the pain medications for penetrating wounds of the skin have a systemic 
effect, and few are effective when given locally. DMSO has never been used follow -
ing direct intrawound administration. The advantages of intrawound administration are that a local rather than systemic effect on pain can be achieved, thus reducing side effects of the medication. One study has reported that damage to the plantar surface of a hind paw in rats 
received intrawound administration of DMSO. 168 Before the closure of the wound, 
DMSO was administered using a sterile pipette at the minimal dose of 10 μL in a 
100% solution and applied deep into the damaged plantar tissue. The application of intrawound DMSO administration resulted in significant control of pain when a thermal hyperalgesia stimulus was applied to the affected paws of the treated rats but not to control rats receiving a placebo. The authors concluded that DMSO appeared effective in the treatment of acute pain and should be further tested in tissue injuries resulting in wound damage and burns. 168
REFERENCES
 1. Huck er HB, Miller JK, Hochberg A, Brobyn RD, Riordan FH, Calesnick B. Studies 
on the absorption, excretion and metabolism of dimethylsulfoxide (DMSO) in man. J Pharmacol Exp Ther. 1967;155(2):309–317. 2. Egorin MJ, Rosen DM, Sridhara R, Sensenbrenner L, Cottler -Fox M. Plasma concentra -
tions and pharmacokinetics of dimethylsulfoxide and its metabolites in patients under -
going peripheral-blood stem-cell transplants. J Clin Oncol. 1998;16(2):610–615. 3. K olb KH, Jaenicke G, Kramer M, Schultze PE. Absorption, distribution and elimination 
of labeled dimethyl sulfoxide in man and animals. Ann NY Acad Sci. 1967;141:85–95. 4. Denk o CW, Goodman RM, Miller R, Donovan T. Distribution of dimethyl sulfoxide-
35S in the rat.
Interstitial edema, low paO2, and complete opacification of lung fields.
What is ARDS characterized by?
To prevent further injury by decreasing neutrophil alveolitis and lung leak.
What is the purpose of using DMSO in treating blunt chest trauma?
To increase hypoxic tolerance of brain slices under hypoxic or ischemic conditions.
What is the purpose of DMSO in treating ARDS?
To quell the cytokine storm and prevent further injury.
What is the purpose of DMSO in treating ARDS?
To relieve pain by blocking the production of certain prostaglandins, which is not possible with traditional pain medications.
What is the purpose of using DMSO in treating pain?