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J. William Myrer, PhD, contributed to conception and design; acquisition and analysis and interpretation of the data; and drafting, critical revision, and final approval of the article. Gary J. Measom, APRN, PhD, contributed to acquisition and analysis and interpretation of the data, and drafting, critical revision, and final approval of the article. Gilbert W. Fellingham, PhD, contributed to conception and design, analysis and interpretation of the data, and critical revision and final approval of the article.
To compare the effectiveness of Nature's Chemist as an ultrasound coupling agent with the effectiveness of another topical analgesic (Biofreeze), Aquasonic 100, and a sham treatment in producing intramuscular (IM) temperature increase during a typical therapeutic ultrasound treatment.
Subjects were randomly assigned to 1 of 4 treatment groups (n = 10 in each group). Groups 1 through 3 received continuous ultrasound at 1.0 W/cm2 for 10 minutes at a frequency of 3 MHz over the posterior calf. Group 4 received a sham treatment. In group 1, we used Aquasonic 100 alone; in group 2, we used a 1:1 (wt/wt) mixture of Biofreeze and Aquasonic 100; in group 3, we used a 1:1 mixture of Nature's Chemist and Aquasonic 100; and in group 4, we used a 1:1 mixture of Aquasonic 100 and Nature's Chemist. In all groups, IM temperature was recorded during the treatment and for 15 minutes posttreatment. We used a modified visual analogue scale to measure each subject's perception of heat at the treatment area during and after treatment.
Forty college students (age, 22.5 ± 2.0 years; height, 175.5 ± 8.0 cm; weight, 71.6 ± 13.1 kg; calf skinfold thickness, 17.8 ± 7.2 mm) volunteered to become subjects.
The IM temperature was recorded at 15-second intervals for 25 minutes at 1 cm below the subcutaneous fat with a thermocouple. Differences were analyzed within and among groups at the beginning of the treatment (T0), the end of the treatment (T10), and 15 minutes posttreatment (T25).
The IM temperature increases in groups 1 through 3 were significantly different from those in group 4 (sham), but they were not significantly different from each other. Temperatures increased in group 1 (Aquasonic 100) by 7.47° ± 1.8°C, in group 2 (Biofreeze and Aquasonic 100) by 6.52° ± 1.6°C, and in group 3 (Nature's Chemist and Aquasonic 100) by 6.99° ± 1.1°C. Temperatures decreased in group 4 (sham) by 0.56° ± 0.3°C. There were no significant differences among groups 1 through 3 in the perception of heat at T5 and T10.
Our results indicate that, at a frequency of 3 MHz and an intensity of 1 W/cm2, Nature's Chemist and Biofreeze mixed in 1:1 ratios with Aquasonic 100 were effective coupling agents. Perceptions of heat by the patient may not indicate actual temperature increases within the muscle.
Two modalities commonly used in the treatment of musculoskeletal trauma are topical analgesics and therapeutic ultrasound.1–3 If the transmission of ultrasound energy is not impaired when using a topical analgesic as a coupling agent and additional therapeutic benefit can be derived from the topical analgesic, it seems only natural that clinicians would wish to combine these treatments. For a topical analgesic to be effective, it would have to possess the properties requisite of a good coupling agent, as well as provide pain relief. In spite of this obvious combination, little research has been done investigating the effectiveness of using topical analgesics as coupling agents. In the studies to date, great disparity has been found in the level of effectiveness of topical analgesics as coupling agents.4–7 For example, Cameron and Monroe7 reported that the 2 popular topical analgesic creams they investigated, Thera-Gesic (Mission Pharmacal Co, San Antonio, TX) and Myoflex (Novartis Consumer Health Inc, Summit, NJ), were at opposite ends of the spectrum with regard to their ability to transmit ultrasound. Thera-Gesic transmitted 97% as much ultrasound energy as that of degassed water, whereas Myoflex transmitted 0%.
A new “100% natural” topical analgesic recently came on the market. The product, Nature's Chemist (Naturopathic Laboratories Intl, Inc, St Petersburg, FL), contains the active ingredient menthol at 16%, combined with oils of eucalyptus, copaiba, citrus, and lavender in a natural lanolin base. The manufacturers of Nature's Chemist, like those of Biofreeze (Performance Health, Inc, Pittsburgh, PA), claim that the product can be used as an effective coupling agent. The primary purpose of our investigation was to compare the effectiveness of Nature's Chemist as an ultrasound coupling agent with the effectiveness of another topical analgesic (Biofreeze), an ultrasound transmission gel (Aquasonic 100 Ultrasound Transmission Gel, Parker Laboratories, Inc, Fairfield, NJ), and a sham treatment in producing intramuscular (IM) temperature increase during a typical therapeutic ultrasound treatment. Secondarily, we examined each group's perception of heat at the treatment site before, during, and after the ultrasound treatment.
Forty college students (age, 22.5 ± 2.0 years; height, 175.5 ± 8.0 cm; weight, 71.6 ± 13.1 kg; posterior calf skinfold thickness, 17.8 ± 7.2 mm) volunteered and signed a consent form approved by the University Human Subject's Institutional Review Board, which also approved the study. Subjects were recruited from the fall classes taught by the primary investigator (J.W.M.) and the coinvestigator (G.J.M.). We verbally screened subjects for a history of peripheral vascular disease, recent or chronic injury to the left calf, allergy to cephalexin hydrochloride, or a known sensitivity to menthol. Subjects with any of these conditions were excluded from the study. Subject data were kept confidential, and only group data were reported. Female subjects were excluded if they were pregnant.
Subjects were randomly assigned to 1 of the 4 treatment groups (10 subjects per group). They were not told which coupling agent they received until they had completed the experiment. To minimize the risk of infection from the insertion of the hypodermic needle microprobes into the intramuscular tissue, we administered a 500-mg dose of cephalexin hydrochloride immediately before the experiment. Each subject took 3 similar doses at 6-hour intervals after the conclusion of the experiment.8
We measured the skinfold thickness of the posterior left lower leg with a Lange Skinfold Caliper (Cambridge Scientific Industries, Ltd, Cambridge, MD). This measurement was divided by 2 to determine the depth of subcutaneous fat over each subject's gastrocnemius muscle. As previous researchers have done, we chose the triceps surae as our site of investigation because of the ease of thermocouple insertion and treatment it affords.3–5,8 Subjects then assumed a prone position on a standard examining table. We shaved a 4 × 4–cm area of skin over the medial portion of the muscle belly of the left calf. We then cleansed the area thoroughly, first with a 10% povidone-iodine scrub, then with a 70% isopropyl alcohol swab.8 Before beginning the study and after each use, we performed high-level disinfection on the 26-gauge hypodermic needle microprobes (Physitemp MT-26/4, Physitemp Instruments, Inc, Clifton, NJ) used to measure IM temperature by placing them in Cidex-Plus (Johnson & Johnson, New Brunswick, NJ) for at least 30 minutes. We washed the Cidex-Plus off the probes with sterile water before inserting them into a subject. An advanced-practice registered nurse (G.J.M.) inserted the probes into the left calf. Insertion depths were controlled by measuring vertically from the posterior surface of the calf with a caliper, 1 cm below the subcutaneous fat covering the middle of the posterior calf. This spot was marked on the skin surface on the medial calf with an ink pen, and the probe was inserted at the marked spot into the medial calf. We then connected the needle microprobe to an electronic thermometer (Columbus Instruments, Iso-Thermex 16-channel, Columbus, OH) and, after 3 minutes, the baseline IM temperature was recorded, and the 10-minute ultrasound treatment began (Figure (Figure1).1). The IM temperature was recorded continuously to the nearest 0.01°C, every 15 seconds throughout the treatment and for 15 minutes posttreatment. Room temperature was monitored during the experiment using a thermocouple (Model TX-31, Columbus Instruments) interfaced to the Iso-Thermex.
Subjects in groups 1 through 3 received continuous ultrasound at 1.0 W/cm2 for 10 minutes at a frequency of 3 MHz over the posterior calf by the same researcher (J.W.M.). The treatment area was standardized by treating within a template that was 2 times the size of the transducer head. The transducer head measured 10 cm2. All groups had 10 g of one of the coupling agents applied to the treatment area during the treatment. Coupling agents were kept at room temperature, 24.1° ± 0.7°C. In group 1 (control group) (age, 22.5 ± 2.4 years; height, 176.0 ± 9.5 cm; weight, 71.6 ± 11.2 kg; calf skinfold thickness, 17.2 ± 8.0 mm), we used Aquasonic 100 alone. In group 2 (age, 22.9 ± 2.1 years; height, 175.3 ± 8.8 cm; weight, 67.4 ± 8.8 kg; calf skinfold thickness, 16.5 ± 6.1 mm), we used a 1:1 (wt/wt) mixture of Biofreeze and Aquasonic 100. In group 3 (age, 22.2 ± 1.7 years; height, 173.4 ± 6.8 cm; weight, 70.5 ± 8.8 kg; calf skinfold thickness, 18.1 ± 7.4 mm), we used a 1:1 mixture of Nature's Chemist and Aquasonic 100. In group 4 (sham group) (age, 22.2 ± 2.1 years; height, 177.4 ± 7.6 cm; weight, 76.7 ± 20.2 kg; calf skinfold thickness, 19.5 ± 7.6 mm), we used a 1:1 mixture of Nature's Chemist and Aquasonic 100. In group 4, the transducer head was rubbed over the treatment area, but the ultrasound machine's intensity was not turned on. The ultrasound unit used for all treatments was a Dynatron 150 (Dynatronics, Salt Lake City, UT), with a beam nonuniformity ratio of 2.67:1. We moved the ultrasound head at the rate of approximately 3 to 4 cm·s−1. At 15 minutes posttreatment, we removed the microprobe and swabbed the area with 70% isopropyl alcohol.
We used a modified visual analogue scale (VAS),9 a continuous line 10 cm in length, to measure each subject's perception of heat at the treatment area. The left end of the scale was labeled “extreme cold,” and the right end of the scale was labeled “extreme heat.” The subjects were asked to mark the scale as soon as the coupling agent was applied (T0), at 5 minutes into the treatment (T5), at the completion of the treatment (T10), and at 15 minutes posttreatment (T25). An identical list of instructions was read by each subject before he or she filled out each VAS. The subject indicated the amount of perceived heat at the treated area by placing a slash somewhere along the VAS. Subjects were not allowed to look at previous VAS trials.
Our independent variables were treatment group and time. Our dependent variables were IM temperature and perception of heat.
Although temperature measurements were available every 15 seconds, the measurements of primary interest were taken at baseline (T0) and at 5-minute intervals for 25 minutes (T5, T10 [end of ultrasound treatment], T15, T20, and T25). As a preliminary test to identify the existence of overall differences among groups, we performed a multivariate analysis of variance (MANOVA) on the 6 time points of interest gathered for each subject. We also calculated the temperature change from baseline to the end of the ultrasound treatment (T10–T0) and from baseline to the end of posttreatment (T25–T0). We performed an analysis of variance (ANOVA) on the temperature changes for both time periods to see if IM temperature increases differed among groups. We used the Duncan multiple-range test as our post hoc test to identify the individual differences among groups. The SAS MIXED procedure (SAS Institute Inc, Cary, NC) was used to determine if there was a difference in the rate of temperature increase among groups during the first 5 minutes of treatment. Measurements at 1-minute intervals were used for this analysis. We performed paired t tests on each treatment group to see if significant temperature changes occurred within each group during the 10-minute ultrasound treatment. We determined the amount of time during which the IM temperature for each group was ≥40°C and performed an ANOVA to see if differences between the groups were significant. We also calculated the maximum temperature increase for each group during the treatment. Significance was set at P < .05 for all tests.
The markings on each VAS were measured to the nearest millimeter, and these values were used in the analysis. We performed a MANOVA on the 4 time points of interest (T0, T5, T10, and T25) gathered for each subject as a preliminary test to identify the existence of overall differences among groups in their perception of heat over the treatment area. This test was followed by separate ANOVAs for each time point of interest. If a significant difference was found between groups, a Duncan multiple-range test was run.
Table Table11 presents the means and standard deviations of IM temperatures for the 4 treatment groups from baseline to the end of the posttreatment period. Figure Figure22 illustrates the average muscle temperature by treatment group over the 25-minute experiment. The MANOVA revealed significant differences among groups over the course of the experiment (F18,88.17 = 12.48, P < .0001). A significant difference in temperature change from baseline to the end of the 10-minute treatment was seen among treatment groups (F3,36 = 83.12, P < .0001). The Duncan multiple-range test revealed that groups 1, 2, and 3 were significantly different from group 4 (sham) but that they were not significantly different from each other. The IM temperature increased in group 1 (Aquasonic 100 alone) by 7.47° ± 1.8°C, in group 2 (Biofreeze and Aquasonic 100) by 6.52° ± 1.6°C, and in group 3 (Nature's Chemist and Aquasonic 100) by 6.99° ± 1.1°C. The IM temperature in group 4 (Nature's Chemist and Aquasonic 100 without ultrasound) decreased by 0.56° ± 0.3°C. All groups' temperature changes from their own baselines to the end of treatment were significant; groups 1 through 3 had significant increases in IM temperature, whereas group 4 had a significant decrease in IM temperature. There was no significant difference in the temperature change from baseline to 15 minutes posttreatment (T25) among treatment groups 1, 2, and 3. There were also no significant differences among groups 1 through 3 in the rate of temperature increase over the first 5 minutes of treatment or in the duration of time for which the IM temperature was ≥40°C.
Table Table22 presents the means and standard deviations of each group's perception of heat at the 4 time points of interest. The MANOVA revealed significant differences among groups over the course of the experiment (F12,87.60 = 4.29, P < .0001). The ANOVA analyzing the groups' perception of heat at the time the coupling agents were applied (T0) indicated no difference among the groups' scores, but at T5 and T10, differences in scores were significant. The Duncan multiple-range tests revealed no differences in scores among groups 1 through 3, but scores in those groups were significantly different from scores in group 4. By T25, 15 minutes posttreatment, once again, the groups' perceptions of heat did not differ.
The practice of combining topical agents with massage is as old as recorded sport medicine. In Athenian society, the paidotribai and aleiptes used various oils and powders to supplement massage in treating the athletes whom it was their business to keep healthy.2 At the turn of the 19th century in America, the first athletic trainers often employed the combination of massage and a counterirritant to “rub down” athletes under their charge.2 Today, we can find many over-the-counter topical analgesics on the market. They are recommended for the temporary relief of minor aches and pains associated with the musculoskeletal system.10 These products enjoy widespread use throughout the sporting spectrum, from the professional football player to the weekend warrior. A 1987 survey conducted by Simmons Market Research Bureau, Inc, in New York revealed that 34% of adults in the United States use topical analgesics.1 The most frequent reasons cited for use were backache, sore muscles, and pain resulting from arthritis or from sports and exercise participation.1
Topical analgesics used in the treatment of athletic injuries are generally divided into 2 categories: counterirritants and trolamine salicylate creams.1 Trolamine salicylate creams are believed to relieve pain by inhibiting prostaglandins at a local level, much as aspirin does systemically. In order for salicylates to work, they must be absorbed through the skin and travel to the target tissues (eg, muscles, ligaments, and joints).1 Topical analgesics can also relieve pain by acting as topical anesthetics. Topical anesthetics inhibit the conduction of any sensory nerve impulses and block the pain receptors by creating numbness in the area of application.11,12 A common example is lidocaine. Most topical analgesics are counterirritants; both Nature's Chemist and Biofreeze are in this category. Counterirritants are agents applied topically that irritate the skin and provide pain relief to underlying tissues such as muscles, ligaments, and viscera.10 The exact mechanism of pain relief is not yet completely understood. Plausible explanations include stimulation of nociceptors, which inhibit the response of central neurons that transmit the pain messages nearby; the gate theory proposed by Melzack and Wall1,13; and the release of endogenous opioid substances.14 Localized vasodilation and subsequent increases in local circulation and tissue temperature are probably related to the latter 2 mechanisms.10,15–20 When applied to the skin, counterirritants provide the classic warmth or coolness of a balm. Among the most common active ingredients found in topical analgesics are menthol, methyl salicylate, camphor, and capsicum.1 These active ingredients are often used in combination with a variety of other inactive ingredients. Many counterirritants can be derived from natural sources; however, most of those used today are synthetically produced.1
Since 1955, the American Medical Association Council on Physical Medicine and Rehabilitation has recommended therapeutic ultrasound as an adjunct to the treatment of pain, soft tissue injury, joint dysfunction, and a variety of musculoskeletal syndromes.19,21,22 Recently, therapeutic ultrasound manufacturers have developed models able to deliver frequencies of 2 and 3 MHz in addition to the traditional 1 MHz.21,22 These higher frequencies allow the clinician to more effectively treat superficial structures.21–23 The factors affecting the absorption of ultrasound energy in tissue include the frequency and intensity of the ultrasound, the duration of treatment, the movement speed of the transducer, the type of tissue being treated, the size of the treatment area, and the coupling agent.19,22
Because of the widespread use of therapeutic ultrasound and topical analgesics in the treatment of musculoskeletal trauma, it seems rational to combine these modalities if no loss in ultrasound energy transmission occurs. Such a combination might save the therapist time, enhance the penetration of the topical agent through the skin and subcutaneous tissue,24 and possibly improve the clinician's management of musculoskeletal injuries. In spite of this obvious combination, little research has investigated the effectiveness of topical analgesics as coupling agents. Cameron and Monroe,7 as well as Benson and McElnay,6 used ultrasound power meters to determine the relative transmission of ultrasound through a number of topical pharmaceutical products, including topical analgesics. Great variation existed, and relatively few products transmitted ultrasound well.
We found only 2 in vivo studies that examined the rise in IM temperature resulting from ultrasound treatments using topical analgesics as coupling agents.4,5 Ashton et al5 investigated the effectiveness of Flex-all 454 (Ari-Med Pharmaceuticals, Tempe, AZ) mixed in a 1:1 combination with ultrasound gel. Subjects received a 10-minute ultrasound treatment with a frequency of 1 MHz at 1.5 W/cm2 on the triceps surae muscle group. At a depth of 3 cm below the skin surface, Ashton et al5 reported a temperature increase of 2.60° ± 0.48°C for the group treated with 1:1 Flex-all and ultrasound gel. The group that was treated with ultrasound gel alone had temperature increases of 3.20° ± 0.58°C. Their sham group experienced a loss of 0.82°C over the treatment period.5 Our sham group had a similar decrease in IM temperature of 0.56°C. The probable reason for this is that the gel, although at room temperature, was colder than the tissue to which it was applied, and through conduction, as with ice, heat was transferred from the body tissues to the coupling agent. Using similar methods, Cosgrove4 reported that a 1:1 mixture of Biofreeze and ultrasound gel increased temperature 1.87° ± 0.76°C at a depth of 3 cm below the skin surface in the triceps surae muscle group. The group treated with ultrasound gel alone had temperature increases of 3.25° ± 0.87°C. Based on these results, one would conclude that these topical analgesics are not effective ultrasound coupling agents.21
Our results differ from those previously reported. We found no significant difference between the amount of IM temperature increase obtained with the ultrasound coupling gel and the topical analgesics. With Nature's Chemist and Biofreeze, significant therapeutic IM heating occurred according to the criteria of both Lehmann et al24 and Draper et al.25 Lehmann et al24 and Warren26 suggested that tissue temperature must be elevated to between 40°C and 45°C to be within the therapeutic range. When treatment fails to raise tissue temperature to 40°C, heating is considered only mild.24,26 If temperatures rise above 45°C, tissue damage is thought to occur.19,22 More recent research suggests that the therapeutic thermal effects of ultrasound may be achieved with less of a temperature increase from baseline than previously thought.25,27 Draper et al25 and Castel27 believed that vigorous heating is obtained with increases of ≥4°C above baseline. Moderate heating is thought to occur with 2° to 3°C increases, and 1°C increases are considered mild heating. Our group treated with Aquasonic 100 alone achieved a mean maximum increase of 7.82°C, whereas the group treated with Nature's Chemist and Aquasonic 100 achieved a 7.75°C maximum increase, and the group treated with Biofreeze and Aquasonic 100 achieved a 6.88°C maximum increase. We calculated the length of time for which each group was within the therapeutic range of Lehmann et al24 (40° to 45°C). The Aquasonic 100 group was within the therapeutic range 8.55 ± 0.82 minutes; the Biofreeze and Aquasonic 100 group, 8.56 ± 1.22 minutes; and the Nature's Chemist and Aquasonic 100 group, 8.93 ± 1.45 minutes.
What are some possible explanations for the differences between our results and previous in vivo experiments investigating the effectiveness of topical analgesics as coupling agents for therapeutic ultrasound? First was the obvious difference in protocol. Our frequencies were different from the frequencies used in other studies. We used 3 MHz, whereas Ashton et al5 and Cosgrove4 used 1 MHz. Benson and McElnay6,28 noted a frequency-dependent attenuation. They found, in general, that as the frequency increased, the topical pharmaceuticals were increasingly able to transmit ultrasound. They postulated that the higher-frequency ultrasound may cause some breakdown of the polymer chains of the topical formulations, which would partially fluidize the formulation's structure, which in turn reduces its ability to attenuate the ultrasound energy.28 Second, Cosgrove4 suggested that during the mixing of the Biofreeze with the ultrasound gel, air may have become entrapped. Aeration severely reduces the effectiveness of ultrasound transmission.29,30 Another difference in protocol was intensity. We used an intensity that was less than the intensity used in previous studies.4,5 One would expect that this intensity would decrease the amount of IM heating, not increase it, as was the case. We also used a different ultrasound machine and a bigger transducer head, 10 cm2 rather than 5 cm2. The templates for all studies were 2 times the size of the transducer head, so the machine differences should have been negligible. The final difference was the depth of the temperature probe: ours was approximately 2 cm below the surface of the skin, whereas the depth used in the other 2 studies was 3 cm. Due to the half-value thickness theorem, one would expect less heating in the deeper tissue.4,31 Less heating did occur, but one would expect that it would affect all coupling agents equally, and therefore, it does not explain our different results.
Analysis of the groups' perception of heat revealed no significant difference among the groups when the coupling agents were initially applied. During treatment (T5) and at the end of treatment (T10), no significant differences were seen among groups 1 through 3, similar to the results noted for IM temperature results, but these groups were significantly different from group 4. It was interesting to note that although at T5 and T10, the Biofreeze and Aquasonic 100 group had a greater perception of heat than either the Aquasonic 100 group or the Nature's Chemist and Aquasonic 100 group, both of these groups actually had higher IM temperatures than the Biofreeze and Aquasonic 100 group, although none of these differences were significant. This same phenomenon was noted by Ashton et al5 with regard to Flex-all and their ultrasound gel group.
At a frequency of 3 MHz and an intensity of 1 W/cm2, Nature's Chemist and Biofreeze mixed 1:1 with Aquasonic 100 are effective coupling agents. Their performance was not statistically different from using Aquasonic 100 alone in terms of producing IM temperature increases. Although the differences were not significant, a 1:1 mixture of Nature's Chemist and Aquasonic 100 increased IM temperatures more rapidly and maintained IM temperatures in the therapeutic range longer than Aquasonic 100 alone or a 1:1 mixture of Biofreeze and Aquasonic 100. Interestingly, perceptions of heat by the patient may not indicate actual temperature increases within the target tissue. Further research should examine the benefits of using topical analgesics that have been shown to be effective coupling agents within patient populations.
We gratefully thank Naturopathic Laboratories Intl, Inc (St Petersburg, FL), for funding this research. We also thank Dynatronics (Salt Lake City, UT) for supplying the ultrasound machine and Parker Laboratories, Inc, for supplying the Aquasonic 100.
The transmissivity of coupling agents used in ultrasound treatments is of concern in clinical practice, as not all media are equally effective.1–5 Dr Myrer and colleagues have succeeded in their effort to assess the effectiveness of 2 commercial preparations as coupling agents for the delivery of ultrasound. This type of work is important because it independently substantiates the claims of manufacturers of the products used by certified athletic trainers and others.
In reading their work, however, I was left asking why the ultrasound transmissivity of a topical analgesic preparation is of concern in clinical practice. The authors state, “…it seems rational to combine these modalities if no loss of ultrasound energy transmission occurs.” Although it is well substantiated that with appropriate settings and technique, ultrasound can elevate the temperature of deep tissues,6 the effects of ultrasound in isolation of other therapeutic interventions have not been well documented.
Furthermore, despite the widespread use of topical analgesic preparations, the mechanism by which they provide pain relief has not been fully elucidated. As suggested by the authors, it is likely that these preparations act via stimulation of cutaneous receptors. Thus, we are left with 2 modalities, one that heats deep tissues and one that stimulates cutaneous receptors. The goal for these treatments can be achieved independently and with minimal additional effort (the time to rub on a topical preparation) on the part of the clinician.
One final possibility is the phonophoresis of an active ingredient, such as trolamine salicylate, into the tissues. Many questions, however, remain regarding the efficacy of this approach. It has not been established that a pharmacologically active dose of such medication can be driven into target tissues by ultrasound or that such a treatment improves the treatment of musculoskeletal injuries.
Therapeutic modalities should be applied to improve clinical outcomes in terms of the rate or extent of recovery, or both. Much more research is needed to determine if the therapeutic modalities applied in contemporary health care truly enhance clinical outcomes. Although the topical preparations applied in this study are effective transmitters of ultrasound, the clinician must decide if such a combination of modalities will facilitate the achievement of treatment goals and enhance treatment outcomes.
We wish to thank Dr Denegar for his commentary and the other anonymous reviewers for their helpful comments during the review process. We appreciate the time and effort required to ensure that a quality product is published in the Journal of Athletic Training.
Concerning the practice of combining topical analgesics with ultrasound, we agree that from a research standpoint, the practice of combining modalities is problematic. Unless properly implemented in a well–thought-out experimental design, it is virtually impossible to determine which treatment or treatments are responsible for any change in the natural history of the condition. From a practical aspect, however, the use of multiple modalities in sequence and in combination is the rule rather than the exception in sport medicine clinics. The reasons for this are perhaps several, ranging from financial remuneration, a saving of time by the therapist, and the lack of scientific evidence to guide the most effective and efficient use of the modalities at the clinician's disposal. This last point is, we believe, the crux of Dr Denegar's commentary and a primary motivating factor in our research. Our research is the first in a series of investigations designed to better understand the efficacy of topical analgesics, used independently and as a coupling agent for ultrasound, in the treatment of musculoskeletal disorders. Part of our planned research agenda includes double-blind, randomized clinical trials. These trials are generally accepted as the paradigm of intervention research.1 This approach gives the strongest scientific proof of the effectiveness of an intervention. By using this method, any new treatment can be compared with either existing or placebo treatments.
We also agree that neither the mechanisms of pain nor the mechanisms by which pain may be reduced by the use of ultrasound or topical analgesics are clearly understood.2–5 The very lack of understanding of these mechanisms is itself a reason for experimenting with a combined treatment of ultrasound and topical analgesics. Because, as Dr Denegar suggests, the mechanisms of pain relief by ultrasound and by topical analgesics are probably different, a combined approach may be more effective, because of a synergistic effect, than their independent use.6 The ultrasound could enhance skin penetration of the active ingredients of the topical analgesic, thereby optimizing its use, and the topical analgesic could enhance the hydration of the skin, thereby increasing the transmission of ultrasound.6,7 As we stated previously, these questions remain unanswered for the time being. It was not the purpose of our experiment, however, to answer any of these questions, but rather, as stated in our paper, to determine the effectiveness of 2 topical analgesics used as coupling agents during a typical therapeutic ultrasound treatment.
One point of clarification, with regard to phonophoresis and the topical analgesics we tested is that neither product contained trolamine salicylate, as might be inferred by reading the commentary. The proposed mechanism of pain relief by menthol (the primary active ingredient in both products: 16% in Nature's Chemist and 3.5% in Biofreeze, as well as 0.2% camphor) is different than that of trolamine salicylate. The proposed mechanism of pain relief by menthol is primarily due to its counterirritant properties. Topically applied counterirritants cause irritation or mild inflammation of the skin to provide pain relief to underlying tissues.3,4,8 A consequence of the mild inflammation produced by the menthol is increased local circulation and tissue temperature, as well as stimulation of local nociceptors.3,4 The stimulation of the skin nociceptors inhibits the transmission of the small, unmyelinated C fibers that transmit pain to the higher brain centers while increasing the input from the large A beta fibers.2–4 This process may also stimulate the release of endogenous opiates.4 The proposed mechanism of pain relief by trolamine salicylate is through its inhibitory effect on prostaglandin biosynthesis at a local level.3,9