Volume 39, Issue 1 , Pages 116-125, January 2010
Efficacy and Side Effects of Diclofenac Patch in Treatment of Patients with Myofascial Pain Syndrome of the Upper Trapezius
Article Outline
Abstract
Locally administered nonsteroidal anti-inflammatory drugs have been widely used in acute soft-tissue damage and articular musculoskeletal pain. This double-blind, placebo-controlled, randomized study was designed to evaluate the efficacy and safety of a topical diclofenac sodium patch in the relief of pain and inflammation as a result of myofascial pain syndrome (MPS) in the upper trapezius. After sample size calculations indicated that 147 patients would be needed to detect a 25% difference between drug and control, 153 patients with MPS were recruited and randomized to receive either a diclofenac sodium patch or control (menthol) patch. Visual analog scale (VAS), cervical active range of motion, pressure pain threshold of the myofascial trigger point (MTrP), patient global assessment, Neck Disability Index, and the occurrence of adverse events were assessed on Day 0 (baseline), Day 4, and Day 8. Use of the diclofenac sodium patch elicited favorable responses for the VAS, cervical active range of motion, and Neck Disability Index by the end of the treatment course (P
<0.05), and was consistently superior to the control patch at all time intervals. No significant differences were observed for the pressure pain threshold of the MTrP for either patch. Tolerability assessment similarly showed the diclofenac patch to be comparatively superior. When assessed at the end of the study, 20 diclofenac patch patients, but only four control patients, considered the tolerability of treatment to be “very good.” Significant differences in adverse reactions were observed between the diclofenac and control patches, with the control patch more likely to produce overall skin irritation. This study demonstrate that the diclofenac sodium patch was superior to the control patch in terms of reducing pain and improving functional outcomes, and did not result in significant adverse effects.
Key Words: Myofascial pain syndrome, diclofenac sodium
Introduction
Myofascial pain syndrome (MPS) refers to a form of muscle pain arising from hyperirritable foci, called myofascial trigger points (MTrPs), at the neuromuscular junction within taut bands of skeletal muscle or ligamentous junctions.1, 2 This syndrome is known to mimic a large number of disorders and is frequently associated with bursitis, tendinitis, hypermobility, fasciitis, radiculopathies, spinal dysfunction, or complex regional pain syndrome.1, 3, 4, 5 It is a common complaint seen in general practice, and its prevalence in patients seeking specialist treatment for pain has been reported to be from 30% to 90%.6 Current management of MPS includes needling therapies, such as acupuncture (“dry needling”), or injection therapy (e.g., lidocaine or botulinum toxin) and noninvasive interventions, such as transcutaneous electrical nerve stimulation, electrical muscle stimulation, laser therapy, and topical anesthetic/analgesic preparations.1, 7, 8
Nonsteroidal anti-inflammatory drugs (NSAIDs) have anti-inflammatory effects, due to the inhibiting of cyclooxygenase, the rate-limiting enzyme in the conversion of arachidonic acid to inflammatory mediators, such as prostaglandins, thromboxanes, and prostacyclins.9, 10 They also inhibit the sensitization of peripheral pain neurons through blocking production of the same mediators, especially prostaglandin E2.11 Topically administered NSAIDs have been shown to be effective in the control of pain from acute soft-tissue damage. They also have been shown to be helpful in controlling articular musculoskeletal pain.2, 12, 13 However, these conditions involve inflammation, and it is not clear to what extent topical formulations of NSAIDs are clinically effective in reducing myofascial pain, which is thought to be due to neuronal hypersensitivity and not to inflammation and/or myositis. Diclofenac is one of the most extensively studied topical NSAIDs in the treatment of pain and inflammation, including pain and inflammation originating from myofascial syndromes.14, 15, 16 The objective of this double-blind, placebo-controlled, randomized study was to evaluate the efficacy and safety of a topical diclofenac sodium patch in the relief of pain as a result of MPS in the upper trapezius; that is, whether it provides prompt and safe amelioration of symptoms, and ensures early mobilization and a minimally affected quality of life.
Methods
Design
Diclofenac sodium patches were compared with control patches in a randomized, double-blind, placebo-controlled trial, and the treatment: control ratio was 2:1. Subjects with clinically confirmed MPS of the upper trapezius were randomized to receive either control or diclofenac sodium patches. These patches were applied on the MTrP area of the upper trapezius three times a day for seven days. Efficacy and safety parameters were assessed before the patch was applied (Day 0), three days (Day 4), and seven days after (Day 8). The study project and consent form were approved by the hospital ethics committee, and informed consent from all the patients was obtained before study initiation.
Subjects
Subjects were recruited from the patients diagnosed with MPS in the upper trapezius at the Department of Physical Medicine and Rehabilitation, Shin Kong Wu Ho-Su Memorial Hospital, and through advertisements in local newspapers. Sample size calculations were based on visual analog scale (VAS) score as the primary endpoint. The assumptions for this calculation were as follows: placebo menthol has a 5% improvement as compared to pure placebo; power of 80% to detect a 25% difference between diclofenac and placebo menthol, at 0.05 (5%) significance level. Different ratios of diclofenac vs. placebo were considered, with the following results: ratio 3:1, total sample size 172, 129 diclofenac, and 43 placebo; ratio 2:1, total sample size 147, 98 diclofenac, and 49 placebo; ratio 1:1, total sample size 130, 65 diclofenac, and 65 placebo. The 2:1 ratio was chosen, which provides the same information as the 1:1 ratio but requires fewer placebo subjects. All the patients recruited participated in the analysis and completed the study (Fig. 1).
Fig. 1
Diagram showing patient flow through the study.
MPS of the upper trapezius was diagnosed according to criteria initially established by Simons et al.,1 and Travell and Simons:5 (1) a well-defined, tender, hypersensitive, palpable nodule located within a taut band of the upper trapezius muscle, and (2) a consistent and reproducible pattern of referred, spontaneous pain (deep, diffuse, and achy pain with localized discomfort that radiated into the lateral aspect of the ipsilateral arm) following a compression with prolonged pressure for 10–20 seconds. To be eligible, patients must have been at least 18 years old at the time of participation, and have presented with a clinically active MTrPs (an active trigger point with spontaneous pain at rest, or pain in response to contraction or stretching of the involved muscle). Exclusion criteria were the following: (1) previous surgical intervention in the same body region; (2) clinical evidence of cervical radiculopathy or myelopathy; (3) history of disc disease, degenerative joint disease, fracture, or dislocation of the cervical vertebrae; (4) history of poor diet, hypothyroidism, or other severe systematic disorders; (5) cognitive deficits or psychiatric illness; (6) use of any oral NSAID or topical medications applied to the painful region since the injury. Subjects with a history of gastrointestinal bleeding or known hypersensitivity to diclofenac were also excluded.
Clinical Sessions
During the initial clinical session, a physician evaluated the patient for diagnostic purposes, and the patient was asked to complete a medical history and demographic questionnaire. The patients were told to perform activities of daily living as much as the condition of their MPS permitted during the period of this study, and that the study would be immediately discontinued should an injury occur in the region being studied. Clinical sessions on Day 0, Day 4, and Day 8 during the one-week treatment course included routine examination of efficacy and safety variables by a research assistant blinded to the study design, and monitoring of the patient diary. The patients were asked to record the pain intensity on the VAS, and to describe any adverse effect in the diary every day and to produce the diary at each session to ensure compliance and completion of the study.
Treatment
The active medication, a diclofenac sodium patch, consisted of 60mg diclofenac sodium in a hydrophilic adhesive applied to nonwoven polyester felt backing. Each patch was 10×14cm in size. The hydrophilic adhesive was composed of gelatin, polyvinyl pyrrolidone, edetate disodium, kaolin, sodium polycrylate, methyl paraben, propyl paraben, tartaric acid, d-sorbitol, and titanium dioxide. Placebo control patches contained menthol and hydrophilic adhesive only. Patches were applied on the skin surface of the affected region in a direction parallel to the muscle fibers of the upper trapezius three times a day for seven days. Since we needed to provide therapy to patients in the control group (for ethical reasons), we provided stretch exercises, one of the most frequently used methods for treating myofascial pain,5 to treat the patients in the control group. The patients were taught stretching exercises for the neck muscles (including upper trapezius, splenius, longissimus, and scalene in both sides) by the same research assistants who performed the efficacy and safety examinations. Rescue medication (acetaminophen) was allowed. The total amount dispensed was recorded at the end of the study when patients returned all used and unused test patches and submitted their usage record in the patient diary.
Efficacy and Safety Variables
Primary Efficacy Outcome VariableThe mean change in pain, measured on a 10-cm VAS, relative to baseline was defined as the primary outcome and used to assess the difference in pain control between the diclofenac sodium and control patch. The left end of the VAS represented “no pain at all,” whereas the right end represented “the most intense pain imaginable or ever experienced.”
Secondary Efficacy Outcome VariablesCervical active range of motion, pressure pain threshold of the MTrP, patient global assessment, and Neck Disability Index were defined as the secondary outcomes.
Cervical active range of motion was measured using a goniometer to record the angle of maximal neck side bending toward the opposite side (maximal stretch of upper trapezius). First, the tester demonstrated the correct movement sequence to the subject. Next, the tester established a neutral position by manually positioning the subject's head until the gravity pointer was at zero. The tester then asked the subject to tilt his or her head as far as possible toward the left or right shoulder until he or she felt tightness or pain. The angle between the neutral position and the end position was measured. Each subject was asked to perform the procedure three times, and the maximal angle was recorded. During the procedure, shoulder raising or head turning was avoided.
Pressure pain threshold of MTrP was measured as previously described.17, 18 A pressure algometer was used for this measurement. The algometer is a manual device with a soft, blunt probe attached to a pressure gauge. It was placed perpendicular to the skin surface in the marked MTrP area. Then, the compression pressure was increased gradually at a rate of 1g/second. The patient was asked to respond to the initial change (increase) of the pain intensity or discomfort by saying “yes” or “pain,” and the compression was then stopped immediately. Then, the scale (kg/cm2) on the algometer was recorded. The average values of three repeated measurements in the interval of 20–60 seconds were calculated for data analyses. The acceptable reliability and sensitivity of this pressure algometer for MTrP measurement have previously been confirmed by Reeves et al.19
The patient global assessment for neck pain consisted of the answer to one question: “How does the relief from neck pain feel at the present time?” scored on a Likert scale (very good=0, good=1, fair=2, poor=3, very poor=4).
The Neck Disability Index is a condition-specific instrument for self-report of neck disability developed and validated by Vernon and Mior.20 It consists of 10 items referring to various activities (personal care, lifting, driving, work, sleeping, concentrating, reading, recreation) and pain (pain intensity, headache) with six possible answers for each item, only one answer to be chosen by the patient for each item. Scores for each item ranged from 0 (no pain and functional limitation) to 5 (worst pain and maximal limitation), resulting in a total score of 0 (not disabled) to 50 (totally disabled).
Safety VariablesPatients were interviewed and examined for adverse effects at Day 0, Day 4, or Day 8 during the one-week treatment course. At the end of each session, the skin where the patch was placed was examined for irritation and other skin reactions. Patients were also asked to report any adverse effects during the study period in their patient diaries. Subjects and investigators were asked to assess the local tolerability of therapy at each clinical session on a scale of 1–4, 1 being very good and 4 being very poor.
Statistical Methods
Continuous data were expressed as mean ± standard deviation, and categorical data were expressed as frequencies or percentages. Baseline characteristics were compared using t-tests, Chi-squared tests, or Fisher's exact tests, depending on their distribution. A mixed-model approach was used for repeated measures, and multiple comparisons were adjusted using the Bonferroni method. Data were analyzed using SAS 9.0 (SAS Institute Inc., Cary, NC, USA), and a P-value <0.05 was considered statistically significant.
Results
Subjects
One hundred fifty-three patients were recruited and randomized into two groups: a treatment group (n=97) and a control group (n=56) (Fig. 1). Mean age was 38.4±10.7 years, and more than 83% were females. Most of the patients were involved in sedentary occupations and less than half presented with bilateral myofascial pain of the upper trapezius. There were no statistically significant differences between the diclofenac and placebo groups for any demographic measure (Table 1).
Table 1. Demographics and Patient Characteristics
| Overall (n=153) | Treatment Group (n=97) | Control Group (n=56) | P | |
|---|---|---|---|---|
| Age (years)a | 38.39±10.73 | 39.57±10.94 | 36.34±10.14 | 0.07 |
| Genderb | 0.08 | |||
| Female | 128 (83.66) | 85 (87.63) | 43 (76.79) | |
| Male | 25 (16.34) | 12 (12.37) | 13 (23.21) | |
| Height (cm)a | 161.47±7.41 | 160.66±7.57 | 162.87±6.99 | 0.08 |
| Weight (kg)a | 57.90±9.50 | 57.91±9.16 | 57.89±10.16 | 0.98 |
| Occupationb | 0.33 | |||
| Sedentary | 114 (75.50) | 69 (72.63) | 45 (80.36) | |
| Manual labor | 37 (24.50) | 26 (27.37) | 11 (19.64) | |
| Medical historyb | 0.74 | |||
| No | 132 (86.27) | 83 (85.57) | 49 (87.50) | |
| Yes | 21 (13.73) | 14 (14.43) | 7 (12.50) | |
| Side of painb | 0.77 | |||
| Bilateral | 69 (45.10) | 43 (44.32) | 26 (46.42) | |
| Left | 45 (29.41) | 29 (29.90) | 16 (28.57) | |
| Right | 39 (25.49) | 25 (25.77) | 14 (25.00) | |
| Patch historyb | 0.12 | |||
| No | 29 (18.95) | 22 (22.68) | 7 (12.50) | |
| Yes | 124 (81.05) | 75 (77.32) | 49 (87.50) | |
| Analgesic useb | 0.23 | |||
| No | 125 (81.70) | 82 (84.54) | 43 (76.79) | |
| Yes | 28 (18.30) | 15 (15.46) | 13 (23.21) | |
at-test. |
bChi-squared test. |
Efficacy
Table 2 lists the data on outcome measures in both treatment and control groups. The treatment group showed significantly better effectiveness than the control group in the VAS (the primary outcome measure), cervical range of motion, and Neck Disability Index. However, there were no significant differences between the two groups in the improvement of pain pressure threshold of MTrP and the patient global assessment for neck pain. Similar results also were found after adjustment for analgesic use (Table 2). Table 3 shows the outcome data presented as the percentage of improvement over baseline in the items in Table 2, showing significant differences between the two groups. By the end of treatment, VAS scores for diclofenac sodium patch had improved by 51.3% (Day 8) compared to baseline values (P<0.01). By the end of treatment, the diclofenac patch was also significantly superior to baseline values for neck mobility and functional disability parameters: that is, the cervical active range of motion (18.4% vs. 6.6%, P<0.01), the Neck Disability Index (32.4% vs. −25.6%, P=0.03), and the patient global assessment (P<0.05). At the last visit, 44 patients in the treatment group said good or very good, whereas only 20 patients in the control group said so. The fourth secondary outcome measure, trigger point sensitivity, showed no significant difference between the two groups.
Table 2. Efficacy Outcomes for Diclofenac Sodium vs. Control Patch
| Treatment Group (n=97) | Control Group (n=56) | P | Padj | |
|---|---|---|---|---|
| VAS (0–10) | <0.01a | <0.01b | ||
| Day 0 | 5.28±2.01 | 5.26±1.94 | ||
| Day 4c | 3.86±1.72 | 4.16±1.76 | ||
| Day 8c, d | 2.57±1.75 | 3.92±1.80 | ||
| Cervical active ROM (degree) | <0.01a | <0.01b | ||
| Day 0 | 37.11±8.10 | 39.93±8.63 | ||
| Day 4 | 40.28±7.17 | 39.25±8.15 | ||
| Day 8c, d | 43.93±7.73 | 42.57±8.24 | ||
| PPT of MTrP (kg) | 0.23 | 0.19 | ||
| Day 0 | 4.23±1.93 | 4.42±1.55 | ||
| Day 4 | 4.37±1.75 | 4.49±1.36 | ||
| Day 8 | 4.93±1.86 | 4.77±1.53 | ||
| PGA (0–4) | 0.23 | 0.20 | ||
| Day 0 | 2.68±0.65 | 2.60±0.71 | ||
| Day 4 | 1.92±0.52 | 1.92±0.56 | ||
| Day 8 | 1.49±0.66 | 1.63±0.65 | ||
| NDI (0–50) | 0.04a | 0.03b | ||
| Day 0 | 16.63±4.11 | 15.79±3.99 | ||
| Day 4c | 13.20±3.11 | 13.13±3.44 | ||
| Day 8c, d | 11.25±2.76 | 11.74±2.86 | ||
aP |
bPadj |
cSignificantly different from Day 0, with Bonferroni adjustment. |
dSignificantly different from Day 4, with Bonferroni adjustment. |
Table 3. Percentage Change of VAS for Pain, Cervical Active ROM, and NDI Over Time for Diclofenac Sodium Patch vs. Placebo
| Time Change | Treatment (%) | Control (%) |
|---|---|---|
| VAS for pain | ||
| Day 4 to Day 0 | −26.90 | −21.21 |
| Day 8 to Day 0 | −51.33 | −25.76 |
| Day 8 to Day 4 | −33.42 | −5.77 |
| Cervical active ROM | ||
| Day 4 to Day 0 | 8.54 | −1.70 |
| Day 8 to Day 0 | 18.38 | 6.61 |
| Day 8 to Day 4 | 16.93 | 8.46 |
| NDI | ||
| Day 4 to Day 0 | −20.63 | −16.85 |
| Day 8 to Day 0 | −32.35 | −25.65 |
Tolerability assessments also showed the diclofenac sodium patch to be significantly superior to the control patch at both Day 4 (18.6% change vs. 10.0% change) and at the end of the study (22.5% change vs. 10.0% change) (P<0.01) (Table 4, Table 5). When assessed at the end of the study, 20 patients in the diclofenac patch group, but only 4 patients in the control group considered the tolerability of treatment to be “very good.”
Table 4. Tolerability of Diclofenac Sodium Patch Over Time vs. Placebo
| Treatment | Control | P | Padj | |
|---|---|---|---|---|
| Tolerability | 0.01a | <0.01b | ||
| Day 0 | 2.31±0.52 | 2.20±0.45 | ||
| Day 4c | 1.88±0.39 | 1.98±0.37 | ||
| Day 8c | 1.79±0.44 | 1.98±0.37 |
aP |
bPadj |
cSignificantly different from Day 0, with Bonferroni adjustment. |
Table 5. Percentage Change in Tolerability Over Time for Diclofenac vs. Placebo Patch
| Time Change | Treatment (%) | Control (%) |
|---|---|---|
| Day 4 to Day 0 | −18.61 | −10.00 |
| Day 8 to Day 0 | −22.51 | −10.00 |
| Day 8 to Day 4 | −4.79 | 0.00 |
Adverse Effects
The overall skin irritation and erythema were seen significantly less frequently in the treatment group than the control group (P<0.05) (Table 6). The most frequently observed adverse effect in either group was skin irritation: with 16%–18% in the control group and 3%–6% in the treatment group. However, all adverse effects had promptly and spontaneously resolved by the end of this study without any treatment.
Table 6. Adverse Reactions from Diclofenac and Placebo Patch Reported at Day 4 and Day 8
| Day 0–Day 4 | Day 4–Day 8 | |||||
|---|---|---|---|---|---|---|
| Treatment Group | Control Group | P | Treatment Group | Control Group | P | |
| Overall skin irritation | 6 (6.19) | 10 (17.86) | 0.03a | 3 (3.09) | 9 (16.07) | 0.01a |
| Dry skin | 1 (1.03) | 0 (0.00) | 1.00 | 0 (0.00) | 0 (0.00) | — |
| Erythema | 0 (0.00) | 1 (1.79) | 0.37 | 0 (0.00) | 3 (5.36) | 0.05a |
| Papule | 0 (0.00) | 0 (0.00) | — | 1 (1.03) | 0 (0.00) | 1.00 |
| Skin itching | 3 (3.09) | 5 (8.93) | 0.14 | 1 (1.03) | 3 (5.36) | 0.14 |
| Cooling sensation | 1 (1.03) | 1 (1.79) | 1.00 | 1 (1.03) | 0 (0.00) | 1.00 |
| Other skin conditionsb | 2 (2.06) | 3 (5.36) | 0.35 | 1 (1.03) | 3 (5.36) | 0.14 |
| Overall GI symptoms | 1 (1.03) | 2 (3.57) | 0.55 | 0 (0.00) | 1 (1.79) | 0.37 |
| Flatus | 1 (1.03) | 1 (1.79) | 1.00 | 0 (0.00) | 0 (0.00) | — |
| Diarrhea | 1 (1.03) | 1 (1.79) | 1.00 | 0 (0.00) | 1 (1.79) | 0.37 |
| Overall CNS symptoms | 1 (1.03) | 2 (3.57) | 0.55 | 1 (1.03) | 3 (5.36) | 0.14 |
| Headache | 1 (1.03) | 1 (1.79) | 1.00 | 0 (0.00) | 1 (1.79) | 0.37 |
| Dizziness | 0 (0.00) | 1 (1.79) | 0.37 | 1 (1.03) | 2 (3.57) | 0.55 |
| Overall others | 1 (1.03) | 0 (0.00) | 1.00 | 0 (0.00) | 1 (1.79) | 0.37 |
| Weakness of the hands | 1 (1.03) | 0 (0.00) | 1.00 | 0 (0.00) | 0 (0.00) | — |
| Less sticky | 0 (0.00) | 0 (0.00) | — | 0 (0.00) | 1 (1.79) | 0.37 |
aP |
bOther skin conditions include pain at untreated side, atopic dermatitis, skin allergy, edema, local pain, change of the pain area, and eyelid edema. |
Discussion
The findings in this double-blind, randomized, placebo-controlled study demonstrate that a one-week treatment with a diclofenac sodium patch produced significantly greater pain reduction and earlier mobilization of the involved muscles than similar treatment with a control menthol patch. The pressure pain threshold of the MTrP, however, was not significantly increased, suggesting that although topical diclofenac resulted in overall local relief of pain, at this dosage and limited treatment time, it did not affect trigger points, which are located at depths of 2–6mm or deeper.4
Topical diclofenac does diffuse into the subdermal tissue. It is a small lipophilic molecule that has been shown to be capable of rapid diffusion through the skin and to distribute in blood, muscle interstitial tissue, and synovial fluid.21 In the form of the 1.16% diethylamine salt (1% diclofenac sodium), absorption occurs continuously through the underlying dermis and subcutaneous tissue to a depth of 3–4mm, and is increased by 3–10 times when an occlusive dressing is used (as in the present case).22 There is a significant direct penetration of diclofenac into skeletal muscle following multiple epicutaneous administrations.23 Plasma concentrations are less than tissue concentrations,23, 24 thus reducing the probability of systemic adverse effects. As an example, when topically administered, maximum plasma levels after a total dose of 86mg diclofenac cream are 100 times less than those after a 50mg dose of oral diclofenac.22 However, when comparing data from different studies on penetration of topical preparations of diclofenac, it must be remembered that the specific formulation of gels, creams, and solutions influences diffusibility, and that many topical formulations have dimethylsulfoxide added to permeabilize the skin barrier and assist the entry of the drug.
The present study differs from most previous studies in that it investigated the action of topical diclofenac on muscle pain not caused by injury and inflammation and therefore focuses on a noninflammatory action of prostaglandins. The peripheral actions of prostaglandins and eicosanaoids in increasing pain are by causing inflammation and by sensitizing the peripheral pain receptors. Most studies of inhibition of these mediators by topical NSAIDs focus on the effect on inflammatory pain. MPS is not an inflammatory lesion, but is an abnormality in the nociceptor response to stimuli. In studies of inflammatory pain, it is not possible to discover what portion of the antinociceptive effect of diclofenac is due to ameliorating inflammation and what part is due to desensitizing the nociceptors.
The latter effect has been studied in normal muscles. Twenty-four hours of diclofenac patch treatment of normal quadriceps muscle significantly increased the pain threshold in this muscle, an effect that was most pronounced in the subjects who were most sensitive to pain.13 This peripheral effect on pain transmission in the absence of inflammation is in accordance with the effect of diclofenac found here in decreasing pain in MPS. Except that although pain decreased and mobility increased in our subjects, we found no change in the sensitivity of the neuronal endings at the trigger points. This discrepancy, however, might be due to the imprecision of the measurement with a pressure algometer in this study.
Previous studies on the use of topical diclofenac have reported, depending on formulation (emulsion cream, gel, or patch), clinically significant amelioration of pain within one to seven days after initiation of therapy, even at low concentrations (0.1%).25, 26 In the report of Predel et al.'s group,25 diclofenac (140mg diclofenac hydroxymethyl pyrolidine patch, two times per day) was significantly better than placebo in resolving the pain of blunt soft-tissue injuries six hours after initiation, and complete pain elimination was observed in a significantly higher proportion (73.3% vs. 6.7%, P<0.0001) of those who underwent diclofenac patch therapy. These findings and the results of this study agree with the general consensus in the literature that topical diclofenac is superior in pain control to placebo.23, 27, 28, 29 In a separate study evaluating 1.16% diclofenac diethylamine gel (4g, 4×/day×3 weeks) for the treatment of osteoarthritis of the knee, Bookman et al. found that topical diclofenac resulted in a better relief of spontaneous pain (VAS) than placebo over Days 1–14 (P<0.02) and better improvements on all efficacy outcomes by the end of the study.27 The use of 1.5% diclofenac (Pennsaid) solution (4× day for 6 weeks) for osteoarthritis of the knee similarly resulted in a significant mean change in pain score and patient global assessment from Day 2 onward, a statistical significance that by Day 42 achieved 0.0003 and 0.0001, respectively. It is noteworthy that a 26.9% (placebo: 21.2%) change was observed in VAS by Day 4 in the present study, despite the comparatively lower dosage (60mg) of diclofenac sodium used.22 It can thus be speculated that improvement in the present study would have been more pronounced had the dosage been somewhat increased and the treatment course extended.
In terms of safety, Predel et al.'s group reported no significant adverse events with diclofenac when compared to placebo.25 Sixteen of 120 patients reported local cutaneous reactions (pruritus and rash) of minor severity. Niethard et al. reported a 9% rate of adverse events in both groups, and a significantly higher rate of local cutaneous reactions, including atopic dermatitis, and Quincke's edema.26 Baer et al. reported only a higher frequency of dry skin (39.3% vs. 21.1%, P=0.004).24 The findings for safety in the present study are in concordance with these findings, although it appears likely, given the equal frequency of adverse effects from both patches, that the skin reactions were due to prolonged application of the hydrophilic adhesive and not diclofenac sodium per se.
Myofascial pain is extremely common in patients with serious illness. Prolonged bed rest may cause muscle disuse and postural problems that can cause or aggravate myofascial pain. Also, nutritional or vitamin deficiencies that are perpetuating factors may be present.5 Since many of these patients are unable to take oral medication and have a reduced tolerance for systemic drugs, a topical preparation to treat myofascial pain could be of great clinical benefit.
The paucity of studies on the use of topical diclofenac in MPS is probably due to the difficulty of conducting studies of this syndrome in a rigorous and orderly manner, and sheds light on the primary limitation of the present study. Studies of the diagnostic reliability of MTrPs have shown interrater reliability to depend on skill and experience. A recent meta-analysis of studies evaluating the reliability of the MPS diagnostic criteria showed reproducibility to be highly variable, and that accurate diagnosis depended on touch, observation, and patient feedback.29 Some allowance should thus be given to this uncertainty, and interpretation cautioned, when considering the findings of this study.
In conclusion, this double-blind, randomized, placebo-controlled study of myofascial pain of the upper trapezius demonstrates that diclofenac sodium patch was superior to placebo in terms of reducing VAS scores and improving functional outcomes, and did not cause significant adverse effects. Further investigation into types of topical diclofenac sodium administration (e.g., emulsion gel, solution, patch) and dosage, especially when compared with other NSAIDs in longer study periods in MPS, is recommended.
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This research was supported by a grant from GlaxoSmithKline Pharmaceuticals, Ltd.
PII: S0885-3924(09)00745-3
doi:10.1016/j.jpainsymman.2009.05.016
© 2010 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.
Volume 39, Issue 1 , Pages 116-125, January 2010
