Research Report
Effects of Ultrasound and Trolamine Salicylate Phonophoresis on Delayed-Onset Muscle Soreness
The purpose of this study was to determine the effects of ultrasound andphonophoresis using an anti-injlammutoy-analgesic cream (tmlamine salicylate) on delayed-onset muscle soreness (DOMS). Repeated eccentric contractions were used to induce DOMS in the elbowjlexom of 40 college-aged women. Subjects were then asn'fined randomly to one of four groups: (1) group 1 (n =10) received sham ultrasound using placebo cream, (2)group 2 (n =10) received sham ultrasound using trolamine salicylate cream, (3) gmup 3 (n =10) received ultrasound using placebo cream, and (4) group 4 (n=IO) received ultrasound using tmlamine salicylate cream. Subjects were treated on 3 consecutive days. Muscle soreness and active eltow range of motion were assessed daily prior to each treatment. The subjects in group 3 experienced an increase in DOMS, whereas no increase in soreness was observed in the subjects in group 4. The authors concluded that ul@asoundenhanced the development of DOMS but that this enhancement was offset by the anti-injlammutoy-anakesic action of salicylate phonophoresis. These findings suggest that salicylate phonophoresis may be useful in clinical situations in which it is desirable to administer ultrasound without increasing injlammution. [Ciccone CD, Leggin BG, CallamumJJ Effects of ultrasound and tmlamine salicylate phonophorea o n delayed-onset muscle soreness. Phys Ther. 1991;71:666-678.]
Charles D Clccone Brian G Leggln John J Callamaro
Key Words: Eccentric muscle contraction, Muscle soreness, Phonophoresis, Tmlamine salicylate, Ultrasound.
Phonophoresis consists of using ultrasound to drive a drug through the skin and into underlying tissues.Ij2In theory, ultrasound can enhance the transdennal delivery of certain pharmacologic agents to skeletal muscle tissue, bursae, tendons, and so on.
Thus, phonophoresis offers the potenrial advantage of delivering a pharmacologic agent in a relatively safe, painless, and easy manner to structures that lie somewhat deep within the body.
CD Ciccone, PhD, PT,is Associate Professor, Department of Physical Therapy, School of Health Sciences and Human Performance, Ithaca College, Ithaca, NY 14850 (USA). Address all correspondence to 1)r Ciccone. BG Leggin and JJ Callamaro were physical therapy students, Program in Physical Therapy, Ithaca College, when this study was conducted. The results of this study were presented in a platform presentation at the Annual Conference of the American Physical Therapy Association, Anaheim, California,June 2428, 1990. This study was approved by the Human Subjects Research Committee of Ithaca College.
Several forms of drugs have been administered with phonophoresis.2~3 Studies using animal models have suggested that ultrasound may enhance the percutaneous absorption of local anesthetics and antiinflammatory steroids. Novak4 documented the ability of ultrasound to increase the amount of lidocaine that was transmitted through the skin and into the quadriceps femoris muscles of rabbits. Ultrasound was able to drive topically administered cortisol to depths of 5 to 6 cm in porcine tissues.5 Studies using human subjects have attempted to document the clinical effectiveness of phonophoresis in treating certain conditions. Griffin et a16 found that
This artick? was submitted December 27, 1990,and was accepted May 6, 1991
Physical TherapyNolume 71, Number 9lSeptember 1991
666 / 39
ultrasonically driven hydrocortisone was superior to ultrasound alone in alleviating pain and inflammation in patients with arthritic disorders. Kleinkort and Woodl found that hydrocortisone phonophoresis was effective in treating patients with various inflammatory conditions. In a case report, Wing7 described using hydrocortisone phonophoresis to treat a patient who had temporomandibular joint pain. Some preliminary evidence, therefore, exists that phonophoresis may improve percutaneous delivery and enhance the effects of local anesthetics and anti-inflammatory steroids. There is, however, a relative paucity of wellcontrolled studies that have evaluated the effectiveness of phonophoresis with other agents. There are essentially no reports of whether ultrasound phonophoresis enhances the analgesic and anti-inflammatory effects of the group of drugs known as salicylates. Salicylates are a family of compounds that includes aspirin (acetylsalicylic acid) and drugs with effects similar to those of aspirin. In general, the salicylates evoke a number of pharmacologic effects, including analgesia and decreased inflammation.8~9These effects are believed to be due to the blockage of the production of prostaglandins.lOJ1 Prostaglandins, which are normally produced locally at the site of injury and infection, play a principal role in mediating the inflammatory response.12J3Aspirin and similar drugs are potent inhibitors of the enzyme that synthesizes prostaglandins. Salicylates are therefore believed to attenuate pain and inflammation through their inhibitory effect on prostaglandin biosynthesis. One type of aspirinlike drug, trolamine salicylate, has been manufactured as a topical cream under a variety of trade names. These preparations typically contain 10% trolamine salicylate and are available without a prescription. Trolamine salicylate creams are applied to the skin's surface so that the drug is absorbed through the skin
and into underlying tissues. The principal desired effect of topically applied salicylates is to decrease pain and inflammation in muscles and other subcutaneous tiss~es.14~15 Investigations in animal models have indicated that a topical application of 10% trolamine salicylate has the ability to penetrate through skin and into muscle tissues even in the absence of ultrasound.14J6If ultrasound can enhance the percutaneous absorption of this drug, phonophoresis may increase its analgesic and antiinflammatory effects. The clinical efficacy of any therapeutic intervention such as salicylate phonophoresis must be determined in some form of sample population. In this study, we elected to use a model of experimentally induced delayed-onset muscle soreness (DOMS). This model has been used previously by investigators15,17to assess various treatment regimens, including the effectiveness of topically applied salicylates. Delayed-onset muscle soreness is described as a sensation of pain and stiffness in skeletal muscle following a session of rigorous o r unaccustomed exerci~e.l5~l~ The term "delayed onset" refers to the fact that peak levels of soreness typically occur around 24 to 72 hours following the exercise session. Delayed-onset muscle soreness does appear, however, to be a transient disorder, and there are no apparent permanent effects of this condition.l8.19 The exact factors responsible for DOMS are not fully understood.18~zO Although earlier theories suggested that this phenomenon is caused by the accumulation of metabolites such as lactic acid, it is now believed that DOMS occurs following the generation of high levels of tension by mus~ 1 e s .Iarge l ~ increases ~ ~ ~ ~in~tension, ~ such as those occurring during eccentric contractions, are believed to alter the structure and transport characteristics of the sarcolemma.18 Alterations in sarcolemmal structure and function may lead to disruption and leakage of the muscle cell membrane as well as activation of proteolytic enzymes that facilitate further intracellular damage
and disarray of myofibrillar struct ~ r e . 1 8 ~ This 2 ~ ~ ~damage 3 to the muscle cell also appears to invoke an inflammatory response, as evidenced by the infiltration of monocytes, subsequent conversion of monocytes to macrophages, and activation of mast cells and histocytes in and around the muscle ce11.24.25 This inflammatory response promotes swelling in the interstitium and leads to the production of nociceptive substances such as kinins, histamine, and prostaglandins.18 The initial damage caused by mechanical factors such as eccentric contractions appears to initiate a series of cellular responses that in turn contribute to the painful symptoms associated with DOMS. The fact that DOMS is associated with symptoms such as pain as well as cellular changes consistent with an inflammatory response makes this phenomenon an acceptable model for studying the effect of nonsteroidal anti-inflammatory-analgesic preparations such as trolamine salicylate.15 We must emphasize that DOMS was induced in our study as an experimental clinical model to test the effectiveness of a specific intervention: salicylate phonophoresis. Our selection of salicylate phonophoresis does not mean that this intervention is necessarily advocated for use in this specific problem (ie, patients exhibiting DOMS), but merely that this model may be helpful in documenting the efficacy of salicylate phonophoresis in a clinical model of musculoskeletal pain and stiffness. The primary purpose of this study was to determine the effect of salicylate phonophoresis as compared with ultrasound used alone on DOMS. We attempted to determine whether phonophoresis increases the effectiveness of trolamine salicylate cream in attenuating the muscle soreness that typically occurs 1 to 2 days after some forms of exercise. The effect of salicylate phonophoresis was compared with the effect of ultrasound used alone to help determine any possible effect of ultrasound on DOMS. This comparison was done so that any ultrasound effects could be distin-
Physical Therapyllrolume 71, Number 9/September 1991
Treatment Creams
-
a Baseline measuremenu: VAS ROM b. Somess Induced c. Treatment
a VAS, ROM measurements b. Treatment
I
I
o
24
I
a VAS, ROM measurements b. Treatment
a VAS, ROM measurements
I
I 48
I
I
n
Figure 1. Ouerview of experimental design. A uisual analogue scale m)was used to measure muscle soreness, and elbow range of motion (ROM) was measured using a goniometer. guished from the pharmacologic effects of trolamine salicylate when both are used together in the form of salicylate phonophoresis.
Subjects The subjects in this study were 40 college-aged women. Only female subjects were selected in order to eliminate any potential gender-related differences in perception of muscle soreness. The subjects were not engaged in any team sports or in a formal weight-training program. All subjects had normal upper-extremity function bilaterally and had not sustained any recent injury to either upper extremity. Each subject provided informed consent in accordance with institutional policy.
Ovewlew of Experimental Deslgn Subjects participated in this study on 4 consecutive days. The procedures used on each day are outlined in Figure 1. Muscle soreness was initiated on day 1 after baseline measurements for muscle soreness and active elbow range of motion (ROM) were recorded. Measurements of muscle soreness and ROM were taken each
succeeding day prior to any other procedure or treatment. Subjects received three consecutive treatments beginning on day 1, with approximately 24 hours separating each treatment. The type of treatment depended on the assigned group for each subject. The last set of measurements taken on day 4 was not followed by a treatment. Specific aspects of the experimental design and procedures are described as follows.
Treatment Groups Subjects were assigned randomly to one of four treatment groups. Each group corresponded to one of the possible combinations of the two principal factors in this study: ultrasound (either sham or real) and treatment cream (either placebo or trolamine salicylate). Subjects in group 1 (n= 10) received sham ultrasound with placebo cream. Group 2 (n= 10) received sham ultrasound with 10% trolamine salicylate cream. Group 3 (n= 10) received ultrasound with placebo cream as the coupling medium. Group 4 (n= 10) received salicylate phonophoresis using ultrasound with 10% trolamine salicylate cream as the coupling medium.
'Thompson Medical Co, PO Box 5264, New York, NY 10150. 'Rich-Mar Corp, PO Box 879, Inola, OK 74036 %OhmicInstruments Co, St Michaels, MD 21663.
Physical Therapy/Volume 71, Number 9/September 1991
The trolamine salicylate cream (Aspercreme*) used in this study contains 10% trolamine salicylate in a base consisting primarily of water and lanolin. The placebo cream we used is a commercially available ultrasound coupling medium (Rich-Mar Lotiont) that is similar in composition and appearance to the trolamine salicylate preparation. Transmission of ultrasound through the placebo cream and the trolamine salicylate cream was measured using an ultrasound power meter (Model UPM-30~). Transmission characteristics of the placebo and salicylate creams are presented in Table 1.
Treatment Procedures One arm of each subject was selected randomly for treatment. The contralatera1 arm served as a comparison (control) within each subject. The designated treatment (according to the subject's assigned group) was applied to the anterior surface of the distal half of the arm and proximal one fourth of the forearm (ie, the distal portion of the muscle belly and the distal attachment of the elbow flexors). This area was typically reported after muscle soreness was initiated on day 1 as the location of greatest soreness in all subjects. Subjects were seated during each treatment with the treated arm supported on an adjacent table. All treatments were given for 5 minutes. A Rich-Mar Model No. lV ultrasound machinet with a lixed frequency of 1 MHz and a 10-cm2sound head was used to administer the treatments. Treatment procedures commenced with the therapist applying a lixed amount (10-12 mL) of either placebo or salicylate cream to the skin and then applying the ultrasound head over the cream using small, continuous, circular movements. For groups receiving ultrasound, treatment was initiated at 1.5 w/cmZof continuous-wave ultrasound, and the intensity was decreased if the subject experienced anything other than a sensation of mild warmth. The duration and intensity of ultrasound
-
Table 1. Transmission Characteristicsof Placebo and Trolamine Salicylate Cream Tested Over the Range of (iltrasound Intensities Used in This Study Transmlsslon Relatlve to Water (%)
Placebo cream
80.0
78.6
88.9
100.0
Trolamine salicylate cream
50.0
50.0
66.8
66.6
treatment were selected based on suggested clinical treatment characteristics,2J6 and the range of intensities used in this study was equivalent to that of intensities used in previous clinical studies using phonophoresis techniques.1~6~7 Sham ultrasound consisted of performing the ultrasound treatment without the machine being turned on. Treatments were given by two therapists (BGL and JJC) using a standardized set of procedures, with the same therapist performing all the treatments on any given subject. Subjects were not informed of the group to which they were assigned and were therefore blinded to both the ultrasound and salicylate treatments. Subjects were unaware of whether ultrasound was applied, because the ultrasound machine was shielded from their view. The salicylate and placebo creams were applied via coded bottles that were identical in appearance. Sdicylate treatment was applied in a double-blind fashion, because the therapist applying the treatment was also unaware of the contents of the applicator bottles.
Inducement of Delayed-Onset Muscle Soreness Repeated eccentric contractions were used to induce DOMS bilaterally in the elbow flexors. The elbow flexors were isolated using a preacher curl bench. This device enabled the subject to sit with her arms resting on a padded board and positioned in front of the body at a 45-degree angle downward from the axilla. Resistance was applied bilaterally to the elbow flexors by having the subject grasp a 42 / 669
barbell and alternately flex and extend both elbows throughout a full ROM. With the subject positioned o n the preacher curl device, a one-repetition maximum (1-RM) of the elbow flexors was determined. The 1-RM represented the amount of weight the subject could lift concentrically one time before the elbow flexors became fatigued. Using a weight equivalent to the 1-RM, the subject performed repeated eccentric contractions of the elbow flexors. Each subject performed only eccentric contractions by slowly lowering the barbell from a fully flexed to a fully extended elbow position. After each eccentric contraction, the weight was returned to a starting position of full elbow flexion by one of the investigators. Each subject performed three sets of 10 repetitions of the exercise, with a 2-minute rest between each set.
Subject's Rating of Muscle Soreness A visual analogue scale (VAS) was used to assess muscle soreness in each subject on each day of the study. The validity and reliability of this tool in measuring experimentally induced pain have been established elsewhere.27 A recent investigationZ8also used a VAS to measure exerciseinduced muscle soreness, thus documenting the application of this tool in measuring DOMS. The VAS used in our study consisted of a continuous horizontal line 150 mm in length, with anchor points of "no soreness" and "worst possible soreness" at the left and right ends of the line, respec-
tively. An identical set of instructions was read to each subject prior to completing each VAS, and subjects indicated the amount of soreness by placing a slash somewhere along the VAS. Relative soreness was then calculated by measuring the distance of the slash from the left end of the VAS. Subjects completed a separate VAS for each upper extremity, and they were not allowed to compare one VAS result with another.
Measurement of Elbow Range of Motion The effect of DOMS on active elbow ROM was determined using a universal goniometer. The goniometer axis was placed over the lateral epicondyle of the humerus, with the stationary and movable arms aligned along the lateral midline of the humerus and the radius, respectively. Active ROM was measured as the total excursion from full elbow flexion to full elbow extension. A standardized testing procedure was established to ensure proper identification of bony landmarks and goniometer alignment. Subjects were given identical instructions prior to each measurement, and a single measurement of total joint excursion was recorded at each session. All ROM measurements were recorded by two therapists (BGL and JJC), with the same therapist performing each measurement on any given subject. The reliability of goniometric measurement of active elbow ROM using this standardized procedure has been established by several investigat0rs.~%3~
Statistical Analysls The VAS values recorded from the treated and control (contralateral) arms of the subjects within each group on each day of the study were compared using a Student's paired t test. This statistical analysis was used to allow a comparison of soreness between each subject's arms without attempting to compare one subject with another or values recorded from one day to another. Differences between the VAS values for the two arms were considered significant at the .05 level of probability.
Physical TherapyNolume 71, Number 9/September 1991
Goniometric measurements of elbow ROM were analyzed for each arm within each group using a two-way analysis of variance (ANOVA). This type of ANOVA was selected to allow comparison of baseline values of elbow ROM recorded on day l for each arm and group to be compared with subsequent values on days 2, 3, and 4. The days of the study were regarded as treatment effects, and subjects were considered as block effects to account for intersubject variability. Post hoc analysis consisted of Duncan's Multiple-Range Test. Differences were considered significant at the .05 level of probability.
"1 1
Changes in muscle soreness, as indicated by the VAS values obtained for the control and treated arms of the subjects in each group on each day of the study, are illustrated in Figure 2. Soreness increased from negligible levels on day 1 to appreciable levels in both arms in all groups by day 2. Most groups reported peak levels of soreness on day 3, reaching levels that ranged between 29% and 45% of the maximum possible rating (150 rnrn). Soreness began to decline toward baseline values by day 4 of the study. The VAS ratings of elbow flexor soreness for the control and treated arms on day 2 through day 4 are presented for each group in Table 2. Baseline soreness levels recorded on day 1 are not shown in the table, because these values were essentially zero for all arms and groups. In group 1, no consistent or significant differences were found between the subjects' treated and control arms throughout the study. In group 2, soreness was essentially the same between the treated and control arms on day 2, but soreness in the treated arm was reported to be 11% less on day 3 and 2 1% less on day 4 relative to the control arm. These differences, however, were not statistically significant. In group 3, soreness in the treated arm was 15%, 25%, and 6% greater in the treated arm versus the control arm on days 2, 3, and 4, respectively. The increased
Control Arm
mG
~1 P Group 2
[1C1Group 3 (t.Group 4
T r e a t e d Arm
Flgure 2. Ratings of elbow P a o r soreness in control (untreated) and mated arms of four subject groups on days 2 to 4 of the study. (Group I =subjects who received sham ultrasound with placebo cream;group 2=subjects who received sham ultrmund with 10% trolamine salicylate cream;group 3=subjects who received ultrasound with placebo cream;group 4=subjects who received ultrasound with 10% trolamine salicylate cream.) soreness in the treated arm of the group 3 subjects on day 3 was significant (PC .05). The subjects in group 4 did not display any consistent or significant differences in soreness between the treated and control arms throughout the study. Results of the goniometric measurement of elbow ROM are shown in Table 3. Elbow ROM in the control arm was significantly reduced relative
Physical TherapyFolume 71, Number 9Beptember 1991
to day 1 baseline values in most groups following inducement of DOMS. In three of the four groups (groups 1, 3 , and 4), ROM in the control arm was significantly reduced on days 2 and 3, with two groups (groups 1 and 3 ) continuing to display a significant decrease on day 4. Elbow ROM values for the control arm in group 2 were not significantly different from one another throughout the 4 days of the study. In the 670 / 43
Table 2. Visual-Analogue-ScalePAS) Measurement of Mwcle Soreness in the Four Experimental Groupf on Day 2 through Day 4 of the Stwr'y VAS lmml
Control Arm
it
Treated Arm SEM
R
SEM
% Dlfferenceb
Group 1 Day 2
29.4
9.2
28.9
9.5
Day 3
42.8
9.0
45.2
11.6
5.6
Day 4
22.6
5.6
19.4
7.3
- 14.2
-1.7
Group 2 Day 2
55.6
10.7
55.2
10.6
-0.7
Day 3
68.0
13.4
60.5
13.7
-11.0
Day 4
33.7
7.7
26.5
6.5
-21.4
Group 3 Day 2
40.1
7.2
45.9
8.7
14.5
Day 3
50.0
13.1
62.3
12.5
24.6
Day 4
35.6
11.9
37.7
12.8
5.9
Group 4 Day 2
51.7
13.3
51.1
11.4
Day 3
48.8
13.8
50.1
13.6
Day 4
32.3
13.9
17.5
6.2
-0.93 -3.OlC -0.46
-1.2 2.7 -45.8
"Group l=subjects who received sham ultrasound with placebo cream; group 2=subjects who received sham ultrasound with 10% trolamine salicylate cream; group 3xsubjects who received ultrasound with placebo cream; group 4=subjects who received ultrasound with 10% trolamine salicylate cream. b%
Difference =
Treated Arm- Control Arm Control Arm
x 100.
CP
Effects of Ultrasound and Trolamine Salicylate Phonophoresis on Delayed-Onset Muscle Soreness
The purpose of this study was to determine the effects of ultrasound andphonophoresis using an anti-injlammutoy-analgesic cream (tmlamine salicylate) on delayed-onset muscle soreness (DOMS). Repeated eccentric contractions were used to induce DOMS in the elbowjlexom of 40 college-aged women. Subjects were then asn'fined randomly to one of four groups: (1) group 1 (n =10) received sham ultrasound using placebo cream, (2)group 2 (n =10) received sham ultrasound using trolamine salicylate cream, (3) gmup 3 (n =10) received ultrasound using placebo cream, and (4) group 4 (n=IO) received ultrasound using tmlamine salicylate cream. Subjects were treated on 3 consecutive days. Muscle soreness and active eltow range of motion were assessed daily prior to each treatment. The subjects in group 3 experienced an increase in DOMS, whereas no increase in soreness was observed in the subjects in group 4. The authors concluded that ul@asoundenhanced the development of DOMS but that this enhancement was offset by the anti-injlammutoy-anakesic action of salicylate phonophoresis. These findings suggest that salicylate phonophoresis may be useful in clinical situations in which it is desirable to administer ultrasound without increasing injlammution. [Ciccone CD, Leggin BG, CallamumJJ Effects of ultrasound and tmlamine salicylate phonophorea o n delayed-onset muscle soreness. Phys Ther. 1991;71:666-678.]
Charles D Clccone Brian G Leggln John J Callamaro
Key Words: Eccentric muscle contraction, Muscle soreness, Phonophoresis, Tmlamine salicylate, Ultrasound.
Phonophoresis consists of using ultrasound to drive a drug through the skin and into underlying tissues.Ij2In theory, ultrasound can enhance the transdennal delivery of certain pharmacologic agents to skeletal muscle tissue, bursae, tendons, and so on.
Thus, phonophoresis offers the potenrial advantage of delivering a pharmacologic agent in a relatively safe, painless, and easy manner to structures that lie somewhat deep within the body.
CD Ciccone, PhD, PT,is Associate Professor, Department of Physical Therapy, School of Health Sciences and Human Performance, Ithaca College, Ithaca, NY 14850 (USA). Address all correspondence to 1)r Ciccone. BG Leggin and JJ Callamaro were physical therapy students, Program in Physical Therapy, Ithaca College, when this study was conducted. The results of this study were presented in a platform presentation at the Annual Conference of the American Physical Therapy Association, Anaheim, California,June 2428, 1990. This study was approved by the Human Subjects Research Committee of Ithaca College.
Several forms of drugs have been administered with phonophoresis.2~3 Studies using animal models have suggested that ultrasound may enhance the percutaneous absorption of local anesthetics and antiinflammatory steroids. Novak4 documented the ability of ultrasound to increase the amount of lidocaine that was transmitted through the skin and into the quadriceps femoris muscles of rabbits. Ultrasound was able to drive topically administered cortisol to depths of 5 to 6 cm in porcine tissues.5 Studies using human subjects have attempted to document the clinical effectiveness of phonophoresis in treating certain conditions. Griffin et a16 found that
This artick? was submitted December 27, 1990,and was accepted May 6, 1991
Physical TherapyNolume 71, Number 9lSeptember 1991
666 / 39
ultrasonically driven hydrocortisone was superior to ultrasound alone in alleviating pain and inflammation in patients with arthritic disorders. Kleinkort and Woodl found that hydrocortisone phonophoresis was effective in treating patients with various inflammatory conditions. In a case report, Wing7 described using hydrocortisone phonophoresis to treat a patient who had temporomandibular joint pain. Some preliminary evidence, therefore, exists that phonophoresis may improve percutaneous delivery and enhance the effects of local anesthetics and anti-inflammatory steroids. There is, however, a relative paucity of wellcontrolled studies that have evaluated the effectiveness of phonophoresis with other agents. There are essentially no reports of whether ultrasound phonophoresis enhances the analgesic and anti-inflammatory effects of the group of drugs known as salicylates. Salicylates are a family of compounds that includes aspirin (acetylsalicylic acid) and drugs with effects similar to those of aspirin. In general, the salicylates evoke a number of pharmacologic effects, including analgesia and decreased inflammation.8~9These effects are believed to be due to the blockage of the production of prostaglandins.lOJ1 Prostaglandins, which are normally produced locally at the site of injury and infection, play a principal role in mediating the inflammatory response.12J3Aspirin and similar drugs are potent inhibitors of the enzyme that synthesizes prostaglandins. Salicylates are therefore believed to attenuate pain and inflammation through their inhibitory effect on prostaglandin biosynthesis. One type of aspirinlike drug, trolamine salicylate, has been manufactured as a topical cream under a variety of trade names. These preparations typically contain 10% trolamine salicylate and are available without a prescription. Trolamine salicylate creams are applied to the skin's surface so that the drug is absorbed through the skin
and into underlying tissues. The principal desired effect of topically applied salicylates is to decrease pain and inflammation in muscles and other subcutaneous tiss~es.14~15 Investigations in animal models have indicated that a topical application of 10% trolamine salicylate has the ability to penetrate through skin and into muscle tissues even in the absence of ultrasound.14J6If ultrasound can enhance the percutaneous absorption of this drug, phonophoresis may increase its analgesic and antiinflammatory effects. The clinical efficacy of any therapeutic intervention such as salicylate phonophoresis must be determined in some form of sample population. In this study, we elected to use a model of experimentally induced delayed-onset muscle soreness (DOMS). This model has been used previously by investigators15,17to assess various treatment regimens, including the effectiveness of topically applied salicylates. Delayed-onset muscle soreness is described as a sensation of pain and stiffness in skeletal muscle following a session of rigorous o r unaccustomed exerci~e.l5~l~ The term "delayed onset" refers to the fact that peak levels of soreness typically occur around 24 to 72 hours following the exercise session. Delayed-onset muscle soreness does appear, however, to be a transient disorder, and there are no apparent permanent effects of this condition.l8.19 The exact factors responsible for DOMS are not fully understood.18~zO Although earlier theories suggested that this phenomenon is caused by the accumulation of metabolites such as lactic acid, it is now believed that DOMS occurs following the generation of high levels of tension by mus~ 1 e s .Iarge l ~ increases ~ ~ ~ ~in~tension, ~ such as those occurring during eccentric contractions, are believed to alter the structure and transport characteristics of the sarcolemma.18 Alterations in sarcolemmal structure and function may lead to disruption and leakage of the muscle cell membrane as well as activation of proteolytic enzymes that facilitate further intracellular damage
and disarray of myofibrillar struct ~ r e . 1 8 ~ This 2 ~ ~ ~damage 3 to the muscle cell also appears to invoke an inflammatory response, as evidenced by the infiltration of monocytes, subsequent conversion of monocytes to macrophages, and activation of mast cells and histocytes in and around the muscle ce11.24.25 This inflammatory response promotes swelling in the interstitium and leads to the production of nociceptive substances such as kinins, histamine, and prostaglandins.18 The initial damage caused by mechanical factors such as eccentric contractions appears to initiate a series of cellular responses that in turn contribute to the painful symptoms associated with DOMS. The fact that DOMS is associated with symptoms such as pain as well as cellular changes consistent with an inflammatory response makes this phenomenon an acceptable model for studying the effect of nonsteroidal anti-inflammatory-analgesic preparations such as trolamine salicylate.15 We must emphasize that DOMS was induced in our study as an experimental clinical model to test the effectiveness of a specific intervention: salicylate phonophoresis. Our selection of salicylate phonophoresis does not mean that this intervention is necessarily advocated for use in this specific problem (ie, patients exhibiting DOMS), but merely that this model may be helpful in documenting the efficacy of salicylate phonophoresis in a clinical model of musculoskeletal pain and stiffness. The primary purpose of this study was to determine the effect of salicylate phonophoresis as compared with ultrasound used alone on DOMS. We attempted to determine whether phonophoresis increases the effectiveness of trolamine salicylate cream in attenuating the muscle soreness that typically occurs 1 to 2 days after some forms of exercise. The effect of salicylate phonophoresis was compared with the effect of ultrasound used alone to help determine any possible effect of ultrasound on DOMS. This comparison was done so that any ultrasound effects could be distin-
Physical Therapyllrolume 71, Number 9/September 1991
Treatment Creams
-
a Baseline measuremenu: VAS ROM b. Somess Induced c. Treatment
a VAS, ROM measurements b. Treatment
I
I
o
24
I
a VAS, ROM measurements b. Treatment
a VAS, ROM measurements
I
I 48
I
I
n
Figure 1. Ouerview of experimental design. A uisual analogue scale m)was used to measure muscle soreness, and elbow range of motion (ROM) was measured using a goniometer. guished from the pharmacologic effects of trolamine salicylate when both are used together in the form of salicylate phonophoresis.
Subjects The subjects in this study were 40 college-aged women. Only female subjects were selected in order to eliminate any potential gender-related differences in perception of muscle soreness. The subjects were not engaged in any team sports or in a formal weight-training program. All subjects had normal upper-extremity function bilaterally and had not sustained any recent injury to either upper extremity. Each subject provided informed consent in accordance with institutional policy.
Ovewlew of Experimental Deslgn Subjects participated in this study on 4 consecutive days. The procedures used on each day are outlined in Figure 1. Muscle soreness was initiated on day 1 after baseline measurements for muscle soreness and active elbow range of motion (ROM) were recorded. Measurements of muscle soreness and ROM were taken each
succeeding day prior to any other procedure or treatment. Subjects received three consecutive treatments beginning on day 1, with approximately 24 hours separating each treatment. The type of treatment depended on the assigned group for each subject. The last set of measurements taken on day 4 was not followed by a treatment. Specific aspects of the experimental design and procedures are described as follows.
Treatment Groups Subjects were assigned randomly to one of four treatment groups. Each group corresponded to one of the possible combinations of the two principal factors in this study: ultrasound (either sham or real) and treatment cream (either placebo or trolamine salicylate). Subjects in group 1 (n= 10) received sham ultrasound with placebo cream. Group 2 (n= 10) received sham ultrasound with 10% trolamine salicylate cream. Group 3 (n= 10) received ultrasound with placebo cream as the coupling medium. Group 4 (n= 10) received salicylate phonophoresis using ultrasound with 10% trolamine salicylate cream as the coupling medium.
'Thompson Medical Co, PO Box 5264, New York, NY 10150. 'Rich-Mar Corp, PO Box 879, Inola, OK 74036 %OhmicInstruments Co, St Michaels, MD 21663.
Physical Therapy/Volume 71, Number 9/September 1991
The trolamine salicylate cream (Aspercreme*) used in this study contains 10% trolamine salicylate in a base consisting primarily of water and lanolin. The placebo cream we used is a commercially available ultrasound coupling medium (Rich-Mar Lotiont) that is similar in composition and appearance to the trolamine salicylate preparation. Transmission of ultrasound through the placebo cream and the trolamine salicylate cream was measured using an ultrasound power meter (Model UPM-30~). Transmission characteristics of the placebo and salicylate creams are presented in Table 1.
Treatment Procedures One arm of each subject was selected randomly for treatment. The contralatera1 arm served as a comparison (control) within each subject. The designated treatment (according to the subject's assigned group) was applied to the anterior surface of the distal half of the arm and proximal one fourth of the forearm (ie, the distal portion of the muscle belly and the distal attachment of the elbow flexors). This area was typically reported after muscle soreness was initiated on day 1 as the location of greatest soreness in all subjects. Subjects were seated during each treatment with the treated arm supported on an adjacent table. All treatments were given for 5 minutes. A Rich-Mar Model No. lV ultrasound machinet with a lixed frequency of 1 MHz and a 10-cm2sound head was used to administer the treatments. Treatment procedures commenced with the therapist applying a lixed amount (10-12 mL) of either placebo or salicylate cream to the skin and then applying the ultrasound head over the cream using small, continuous, circular movements. For groups receiving ultrasound, treatment was initiated at 1.5 w/cmZof continuous-wave ultrasound, and the intensity was decreased if the subject experienced anything other than a sensation of mild warmth. The duration and intensity of ultrasound
-
Table 1. Transmission Characteristicsof Placebo and Trolamine Salicylate Cream Tested Over the Range of (iltrasound Intensities Used in This Study Transmlsslon Relatlve to Water (%)
Placebo cream
80.0
78.6
88.9
100.0
Trolamine salicylate cream
50.0
50.0
66.8
66.6
treatment were selected based on suggested clinical treatment characteristics,2J6 and the range of intensities used in this study was equivalent to that of intensities used in previous clinical studies using phonophoresis techniques.1~6~7 Sham ultrasound consisted of performing the ultrasound treatment without the machine being turned on. Treatments were given by two therapists (BGL and JJC) using a standardized set of procedures, with the same therapist performing all the treatments on any given subject. Subjects were not informed of the group to which they were assigned and were therefore blinded to both the ultrasound and salicylate treatments. Subjects were unaware of whether ultrasound was applied, because the ultrasound machine was shielded from their view. The salicylate and placebo creams were applied via coded bottles that were identical in appearance. Sdicylate treatment was applied in a double-blind fashion, because the therapist applying the treatment was also unaware of the contents of the applicator bottles.
Inducement of Delayed-Onset Muscle Soreness Repeated eccentric contractions were used to induce DOMS bilaterally in the elbow flexors. The elbow flexors were isolated using a preacher curl bench. This device enabled the subject to sit with her arms resting on a padded board and positioned in front of the body at a 45-degree angle downward from the axilla. Resistance was applied bilaterally to the elbow flexors by having the subject grasp a 42 / 669
barbell and alternately flex and extend both elbows throughout a full ROM. With the subject positioned o n the preacher curl device, a one-repetition maximum (1-RM) of the elbow flexors was determined. The 1-RM represented the amount of weight the subject could lift concentrically one time before the elbow flexors became fatigued. Using a weight equivalent to the 1-RM, the subject performed repeated eccentric contractions of the elbow flexors. Each subject performed only eccentric contractions by slowly lowering the barbell from a fully flexed to a fully extended elbow position. After each eccentric contraction, the weight was returned to a starting position of full elbow flexion by one of the investigators. Each subject performed three sets of 10 repetitions of the exercise, with a 2-minute rest between each set.
Subject's Rating of Muscle Soreness A visual analogue scale (VAS) was used to assess muscle soreness in each subject on each day of the study. The validity and reliability of this tool in measuring experimentally induced pain have been established elsewhere.27 A recent investigationZ8also used a VAS to measure exerciseinduced muscle soreness, thus documenting the application of this tool in measuring DOMS. The VAS used in our study consisted of a continuous horizontal line 150 mm in length, with anchor points of "no soreness" and "worst possible soreness" at the left and right ends of the line, respec-
tively. An identical set of instructions was read to each subject prior to completing each VAS, and subjects indicated the amount of soreness by placing a slash somewhere along the VAS. Relative soreness was then calculated by measuring the distance of the slash from the left end of the VAS. Subjects completed a separate VAS for each upper extremity, and they were not allowed to compare one VAS result with another.
Measurement of Elbow Range of Motion The effect of DOMS on active elbow ROM was determined using a universal goniometer. The goniometer axis was placed over the lateral epicondyle of the humerus, with the stationary and movable arms aligned along the lateral midline of the humerus and the radius, respectively. Active ROM was measured as the total excursion from full elbow flexion to full elbow extension. A standardized testing procedure was established to ensure proper identification of bony landmarks and goniometer alignment. Subjects were given identical instructions prior to each measurement, and a single measurement of total joint excursion was recorded at each session. All ROM measurements were recorded by two therapists (BGL and JJC), with the same therapist performing each measurement on any given subject. The reliability of goniometric measurement of active elbow ROM using this standardized procedure has been established by several investigat0rs.~%3~
Statistical Analysls The VAS values recorded from the treated and control (contralateral) arms of the subjects within each group on each day of the study were compared using a Student's paired t test. This statistical analysis was used to allow a comparison of soreness between each subject's arms without attempting to compare one subject with another or values recorded from one day to another. Differences between the VAS values for the two arms were considered significant at the .05 level of probability.
Physical TherapyNolume 71, Number 9/September 1991
Goniometric measurements of elbow ROM were analyzed for each arm within each group using a two-way analysis of variance (ANOVA). This type of ANOVA was selected to allow comparison of baseline values of elbow ROM recorded on day l for each arm and group to be compared with subsequent values on days 2, 3, and 4. The days of the study were regarded as treatment effects, and subjects were considered as block effects to account for intersubject variability. Post hoc analysis consisted of Duncan's Multiple-Range Test. Differences were considered significant at the .05 level of probability.
"1 1
Changes in muscle soreness, as indicated by the VAS values obtained for the control and treated arms of the subjects in each group on each day of the study, are illustrated in Figure 2. Soreness increased from negligible levels on day 1 to appreciable levels in both arms in all groups by day 2. Most groups reported peak levels of soreness on day 3, reaching levels that ranged between 29% and 45% of the maximum possible rating (150 rnrn). Soreness began to decline toward baseline values by day 4 of the study. The VAS ratings of elbow flexor soreness for the control and treated arms on day 2 through day 4 are presented for each group in Table 2. Baseline soreness levels recorded on day 1 are not shown in the table, because these values were essentially zero for all arms and groups. In group 1, no consistent or significant differences were found between the subjects' treated and control arms throughout the study. In group 2, soreness was essentially the same between the treated and control arms on day 2, but soreness in the treated arm was reported to be 11% less on day 3 and 2 1% less on day 4 relative to the control arm. These differences, however, were not statistically significant. In group 3, soreness in the treated arm was 15%, 25%, and 6% greater in the treated arm versus the control arm on days 2, 3, and 4, respectively. The increased
Control Arm
mG
~1 P Group 2
[1C1Group 3 (t.Group 4
T r e a t e d Arm
Flgure 2. Ratings of elbow P a o r soreness in control (untreated) and mated arms of four subject groups on days 2 to 4 of the study. (Group I =subjects who received sham ultrasound with placebo cream;group 2=subjects who received sham ultrmund with 10% trolamine salicylate cream;group 3=subjects who received ultrasound with placebo cream;group 4=subjects who received ultrasound with 10% trolamine salicylate cream.) soreness in the treated arm of the group 3 subjects on day 3 was significant (PC .05). The subjects in group 4 did not display any consistent or significant differences in soreness between the treated and control arms throughout the study. Results of the goniometric measurement of elbow ROM are shown in Table 3. Elbow ROM in the control arm was significantly reduced relative
Physical TherapyFolume 71, Number 9Beptember 1991
to day 1 baseline values in most groups following inducement of DOMS. In three of the four groups (groups 1, 3 , and 4), ROM in the control arm was significantly reduced on days 2 and 3, with two groups (groups 1 and 3 ) continuing to display a significant decrease on day 4. Elbow ROM values for the control arm in group 2 were not significantly different from one another throughout the 4 days of the study. In the 670 / 43
Table 2. Visual-Analogue-ScalePAS) Measurement of Mwcle Soreness in the Four Experimental Groupf on Day 2 through Day 4 of the Stwr'y VAS lmml
Control Arm
it
Treated Arm SEM
R
SEM
% Dlfferenceb
Group 1 Day 2
29.4
9.2
28.9
9.5
Day 3
42.8
9.0
45.2
11.6
5.6
Day 4
22.6
5.6
19.4
7.3
- 14.2
-1.7
Group 2 Day 2
55.6
10.7
55.2
10.6
-0.7
Day 3
68.0
13.4
60.5
13.7
-11.0
Day 4
33.7
7.7
26.5
6.5
-21.4
Group 3 Day 2
40.1
7.2
45.9
8.7
14.5
Day 3
50.0
13.1
62.3
12.5
24.6
Day 4
35.6
11.9
37.7
12.8
5.9
Group 4 Day 2
51.7
13.3
51.1
11.4
Day 3
48.8
13.8
50.1
13.6
Day 4
32.3
13.9
17.5
6.2
-0.93 -3.OlC -0.46
-1.2 2.7 -45.8
"Group l=subjects who received sham ultrasound with placebo cream; group 2=subjects who received sham ultrasound with 10% trolamine salicylate cream; group 3xsubjects who received ultrasound with placebo cream; group 4=subjects who received ultrasound with 10% trolamine salicylate cream. b%
Difference =
Treated Arm- Control Arm Control Arm
x 100.
CP
