Massage — With Your Genes On

Abstract & Commentary

By Russell H. Greenfield, MD

Synopsis: Through a small but exquisite study, the authors of this investigatory intervention trial provide a plausible subcellular explanation for massage therapy's purported benefits on injured muscle using muscle biopsy and subsequent gene profiling. The application of similar study techniques might be expected in future studies of other CAM therapies directed against pain.

Source: Crane JD, et al. Massage therapy attenuates inflammatory signaling after exercise-induced muscle damage. Sci Trans Med 2012;119:1.

The aim of this study was to assess the influence of massage therapy within muscle that had completed a bout of intense exercise. Eleven recreationally active (and brave!) male volunteers participated in the study. After an overnight fast, subjects reported to the laboratory on two separate occasions, 14 days apart. They were permitted to follow their normal diets up until fasting, but were asked to abstain from moderate to intense physical exertion for 72 hours prior, alcohol consumption for 48 hours, and caffeine ingestion for the previous 12 hours. A 355-kcal defined formula diet was ingested 2 hours before each study session.

At the beginning of the first visit, a baseline muscle biopsy was taken from the quadriceps muscle of a randomly assigned leg to serve as the resting control sample. After the biopsy, each subject underwent testing for peak aerobic capacity (VO2peak) on an upright bicycle ergometer.

At the second visit, subjects performed a bout of exhaustive aerobic exercise followed by randomized massage therapy. The exercise activity again consisted of upright cycling and was performed as follows: 1) pedaling at a workload calculated to elicit 60% of each subject's predetermined VO2peak for 30 minutes at 70-90 rpm, followed by 2) an increase in exercise intensity to a workload equivalent to 65% VO2peak for 5 minutes, then 3) back down to 60% for 5 minutes, and 4) increased to 70% VO2peak for 5 minutes, then 5) dropped to 60% for 5 minutes, and 6) so on until a maximum of 85% VO2peak was achieved. Exercise was continued until participants reached exhaustion, defined as the inability to maintain a cycling cadence above 70 rpm.

Subjects were allowed to recover for 10 minutes while massage oil was lightly applied to both quadriceps. One leg was then selected at random to receive 10 minutes of massage from a registered massage therapist. Repeat quadriceps muscle biopsies were obtained immediately after massage therapy, and then after 2.5 hours of additional recovery time.

Whole-genome, untargeted microarrays were performed initially to screen for expressed genes induced by massage; five were identified that were differentially expressed in the muscle immediately after massage, and four genes that were differentially expressed 2.5 hours after treatment. Real-time reverse transcription–polymerase chain reaction (RT-PCR), protein signaling analysis, and metabolite quantification were performed to characterize processes occurring within the muscle in association with massage.

The authors describe a pathway starting with myofibrillar damage as a result of exercise-induced muscle contractions or direct trauma, and ending with localized inflammation and resultant pain; in between there lies a complex interplay of mechanotransduction, cell signaling, activation and suppression of regulatory proteins, immune cell recruitment, and alterations in glucose uptake. The authors do a terrific job of describing this in a detailed yet accessible manner. The bottom line results emphasize the sub-cellular and molecular levels: massage therapy appears to 1) drive processes that modulate inflammation, in part by reducing the synthesis of pro-inflammatory cytokines (which may interfere with muscle repair), and 2) promote repair of damaged muscle tissue by improving contractile function, enhancing glucose uptake, reducing intracellular stress, promoting protein synthesis, and increasing the production of mitochondria. The temporal nature of the findings suggest that processes related to cytoskeletal integrity take place early following massage therapy, while those impacting inflammation occur later. Of note, no changes in glycogen fractions and muscle lactate levels were identified.

The authors close by stating that massage therapy may work in ways similar to NSAIDs, yet be safer, and potentially more effective in addressing muscle injury, especially to areas of known low blood flow such as the muscle-tendon interface. The mechanisms by which massage therapy provides therapeutic benefits include increased mitochondrial production, enhanced protein synthesis, and modulation of pro-inflammatory cytokines.

Commentary

Everyone knows that massage therapy feels good, and numerous studies show that massage can contribute to recovery from a variety of painful conditions, but only rarely are subjective outcomes sufficient to carry the day when it comes to determining precise clinical indications, or helping patients to secure insurance reimbursement for treatment. It has long been presumed that massage therapy helps relieve aching, overworked, and damaged muscles through a combination of actions that promote increased blood flow and clearance of lactic acid buildup, among others, but in truth there has been relatively little mechanistic research performed that focuses on how massage therapy, and other CAM interventions, might provide relief. And then this paper was published.

Creating a biological understanding of therapeutic impact related to any therapy is imperative. Scientific inquiry into CAM treatments that takes advantage of technological advances in molecular biology and genetics is rare. There are reasons, of course, but the fact remains. The results of this study show it can, and should, be done more frequently.

The researchers confirmed first that damage had been done to cells of the quadriceps muscle through toluidine blue staining. On a molecular level, they then showed that a mere 10 minutes of massage therapy created changes that decrease inflammation, hasten muscle repair, decrease pain, and promote recovery. Some of these actions are unique, some are similar to those associated with the use of anti-inflammatory medication, but few would argue with the idea that massage therapy is infinitely more enjoyable than popping pills, and significantly safer.

Kudos to the researchers (and the courage and vitality of the volunteers) for a study that not only offers answers that may pave the way for greater advantage for patients, but also lights the path for more in-depth biological evaluation of additional therapies, both conventional and alternative in nature.