Topical menthol gels are classified “topical analgesics” and are claimed to relieve minor aches and pains of the musculoskeletal system. In this study we investigate the acute effect of topical menthol on carpal tunnel syndrome (CTS). We screened 645 slaughterhouse workers and recruited 10 participants with CTS and chronic pain of the arm/hand who were randomly distributed into two groups to receive topical menthol (Biofreeze) or placebo (gel with a menthol scent) during the working day and 48 hours later the other treatment (crossover design). Participants rated arm/hand pain intensity during the last hour of work (scale 0–10) immediately before 1, 2, and 3 hours after application. Furthermore, global rating of change (GROC) in arm/hand pain was assessed 3 hours after application. Compared with placebo, pain intensity and GROC improved more following application of topical menthol (
Carpal tunnel syndrome (CTS) is a neuromuscular condition caused by increased pressure on the median nerve at the level of the wrist and accounts for approximately 90% of all entrapment neuropathies [
Conservative treatment is usually offered to individuals with mild to moderate intermittent symptoms of CTS, whereas surgical carpal tunnel release is the preferred treatment of patients with persistent CTS symptoms and those not responding to conservative treatment [
Menthol possesses weak analgesic properties when applied to the site of musculoskeletal injury and topical gel containing menthol is thus used as analgesics [
Johar and coworkers [
The aim of the study was to evaluate the acute effect of topical menthol and placebo (gel with a menthol scent) on pain in slaughterhouse workers with chronic pain and symptoms of carpal tunnel syndrome.
This triple-blind randomized placebo-controlled crossover trial evaluates the acute effect of topical menthol (Biofreeze) and placebo (gel with a menthol scent) on chronic pain in Danish slaughterhouse workers with symptoms of carpal tunnel syndrome. The study was approved by The Danish National Ethics Committee on Biomedical Research (Ethical Committee of Frederiksberg and Copenhagen; H-3-2010-062) and registered in ClinicalTrails.gov (
Recruitment was established on subjects excluded from participation in another randomized controlled trial [
The recruitment was as follows. A screening questionnaire was administered to 645 Danish slaughterhouse workers (aged 18–67 years). In total 595 individuals replied to the questionnaire of which 410 were interested to participate in the research project. The initial inclusion criteria based on the screening questionnaire were (1) currently working at a slaughterhouse for at least 30 hours a week, (2) pain intensity in the shoulder, elbow/forearm, or hand/wrist of 3 or more on a 0–10 VAS scale during the last 3 months, (3) stating at least “
A total of 135 employees presented for the baseline clinical examination. Exclusion criteria were hypertension (Systolic BP
Based on the clinical examination and associated questionnaire, 69 workers were excluded due to contraindications of which 19 showed symptoms of carpal tunnel syndrome. Symptoms of carpal tunnel syndrome included (1) nocturnal numbness of the hand; (2) paresthesia in the distribution of the median nerve; (3) positive Tinel’s sign over the carpal tunnel; (4) positive Phalen’s test; (5) decreased sensibility in the distribution of median nerve; (6) decreased strength in abduction of the thumb; (7) pain intensity of at least 4 in the hand/wrist; and (8) the pain should have lasted at least 3 months. Participants should fulfill all these eight criteria to be defined as having carpal tunnel syndrome. The 19 workers with symptoms of carpal tunnel syndrome were invited to participate in the present study and 10 workers willingly accepted. Figure
Participants flow. CTS denotes carpal tunnel syndrome.
Using a computer generated random numbers table, participants were randomly distributed into two groups to receive either topical menthol (Biofreeze) or placebo on the first day of testing at a 1 : 1 menthol/placebo ratio. Interspersed by a minimum of 48 hours, participants received the other treatment (crossover design) on the second day of testing.
Both the active treatment (topical menthol gel) and placebo (gel with a menthol scent) were provided by The Hygenic Corporation (Akron, OH).
Menthol and placebo gels were prepared by technicians from The Hygenic Corporation who also verified proper labeling of the gel tubes with corresponding allocation code. The menthol and placebo gels were packaged and labeled in the same manner, so that each topical gel tube resembled the other. The menthol and placebo topical gels, which had no other identifiers, were delivered to a blinded study administrator at the National Research Centre for the Working Environment and further delivered by hand to the research assistant who administered the treatment and recorded the allocation on a separate case report form. Following data collection and statistical analyses the allocation code was broken by The Hygenic Corporation and delivered to the researchers at the National Research Centre for the Working Environment.
Participants were invited for two separate days of testing involving topical application of menthol or placebo to the arm, wrist, and hand. On the first day of testing, participants were randomly allocated to receive either topical menthol (Biofreeze) or placebo (gel with a menthol scent) and on the second day of testing, participants received the contrasting treatment, thus acting as their own controls in a crossover design.
The Biofreeze topical gel contained 4% active menthol and the following ingredients:
Menthol and placebo were applied topically to the hand and wrist by a blinded research assistant at a recommended dosage of 2.5 mL per 500 cm2 [
The primary outcome was the change in arm/hand pain intensity (scale 0–10) during work. The participant rated “pain intensity during the last hour” on the 0–10 modified VAS scale (where 0 indicates “no pain at all” and 10 indicates “worst pain imaginable”) immediately before and 1, 2, and 3 hours after application of the gel [
Power calculations showed that 10 participants in a paired crossover design were necessary for testing the null hypothesis of equality of treatment at an alpha level of 5%, a statistical power of 80%, a minimal relevant difference in hand/wrist pain intensity of 1.5, and SD of 1.5 on a scale of 0–10.
Statistical analyses were performed using the SAS statistically software for Windows (SAS Institute, Cary, NC). The primary outcome (change in hand/wrist pain) was analyzed according to intention-to-treat principle using a repeated measures
An alpha level of 0.05 was used for statistical significance. The primary outcome variable (change in hand/wrist pain) is reported as between-group least square mean differences and 95% confidence intervals from before to after (average of 1, 2, and 3 hours after) application of the gel. The secondary outcome variable is reported as between-group least square mean differences and 95% confidence intervals. Finally we calculated effect size as Cohen’s d [
Table
Baseline characteristics of the participants. Values are means (SD).
Demographics | |
Height, cm | 173 (7) |
Weight, kg | 80 (21) |
Body mass index, kg m−2 | 26 (5) |
Age, year | 45 (7) |
Number of men/women | 8/2 |
Clinical | |
Elbow/forearm pain intensity during the last week (scale 0–10) | 6.3 (2.3) |
Hand/wrist pain intensity during the last week (scale 0–10) | 5.7 (2.8) |
Arm/hand pain intensity during the last hour of work (scale 0–10) | 4.3 (1.8) |
Days with pain during the last week | 5.8 (1.9) |
Figure
Changes in arm/hand pain intensity and global rating of change (GROC) following menthol and placebo topical application. Differences of each group are shown on the left and post hoc contrasts between the groups on the right. Values are means (95% confidence interval).
Within-group difference from before to after application | Between-group difference | |||
---|---|---|---|---|
Menthol | Placebo | Menthol versus placebo |
|
|
Pain at hour 1 (0–10) | −1.3 (−2.2 to −0.4) | −0.1 (−1.0 to 0.8) | −1.2 (−2.1 to −0.2) | 0.016 |
Pain at hour 2 (0–10) | −1.4 (−2.3 to −0.5) | −0.3 (−1.2 to 0.6) | −1.1 (−2.0 to −0.1) | 0.027 |
Pain at hour 3 (0–10) | −1.3 (−2.2 to −0.4) | 0.0 (−0.9 to 0.9) | −1.3 (−2.2 to −0.3) | 0.009 |
GROC (−5 to 5) | −1.2 (−2.4 to −0.1) | 0.3 (−0.9 to 1.4) | −1.5 (−2.9 to −0.1) | 0.044 |
Change in arm/hand pain following application of topical menthol (menthol) or topical placebo (placebo) before (time 0) and 1, 2, and 3 hours following application.
Analysis of variance showed a
This triple-blind, randomized placebo-controlled trial found that topical gel containing menthol applied to the hand and arm acutely reduced chronic pain among slaughterhouse workers with carpal tunnel syndrome. The effect persisted all three hours of the experiment.
Topical gel containing menthol led to a 31% (1.3 point on 0–10 VAS) acute reduction in chronic pain associated with carpal tunnel syndrome, and the absolute change in pain symptoms between topical menthol and placebo was 1.2 corresponding to a moderate effect size (Cohen’s
Menthol based topical applications are a widely used analgesic compound acting at the peripherally located site of injury. Zhang et al. [
Menthol applied to the skin increases the sensitization of thermosensitive neurons by activation of the TRPM8 channel consequently leading to the perception of coolness, which has an inhibitory effect on nociceptive afferents and on dorsal-horn neurons conducting pain impulses to the thalamus [
Workplace risk factors for the development of CTS involve repetitive and forceful hand use, and the prevalence of CTS among Danish slaughterhouse workers was found to be almost 4 times that of reference workers [
The randomized, triple-blind placebo-controlled crossover design protects against systematic bias. As we did not measure nerve conduction velocity or ultrasound waves over the carpal tunnel we were not able to conclusively establish the diagnose of carpal tunnel syndrome. However, to be regarded as a worker with symptoms of carpal tunnel syndrome all participants were to experience all of the following symptoms: (1) nocturnal numbness of the hand; (2) paresthesia in the distribution of the median nerve; (3) positive Tinel’s sign over the carpal tunnel; (4) positive Phalen’s test; (5) decreased sensibility in the distribution of median nerve; (6) decreased strength in abduction of the thumb; (7) pain intensity of at least 4 in the hand/wrist; and (8) pain that lasted at least 3 months. A limitation of the study is that only subjective rating scales are used as outcome variables. However, even without objective measures to support the subjective variables, the triple-blind, placebo-controlled design eliminates the probability of a placebo effect. The exclusion and inclusion criteria used in the present study confine the generalizability of our results to workers with chronic pain and symptoms of carpal tunnel syndrome exposed to highly and repetitive and forceful work. The size of the study allows us to test the effectiveness of topical menthol, but for evaluating adverse events a much larger study is needed. However, topical gels are generally considered safe.
Topical menthol application acutely reduces pain intensity among slaughterhouse workers with chronic pain and symptoms of carpal tunnel syndrome compared with placebo. Thus, topical menthol should be considered as an effective nonsystemic alternative to regular analgesics in the workplace management of chronic, localized musculoskeletal, and neuropathic pain.
The authors declare that there is no conflict of interests regarding the publication of this paper.
The authors would like to thank Stine Dam Søndergaard for valuable practical help during the data collection. Furthermore, thanks are due to the Hygenic Corporation for supporting this study.