Massage, mitochondria, inflammation

I’ve received some good questions after the release of our recent study on the interaction of exercise and massage (1), but the question most relevant to this site is whether or not we would anticipate a similar result if we used strength training instead of endurance exercise. Definitely a good question, and to address it I’ll start with a short summary of the massage study itself and follow up with some points that are relevant to the use of massage following a strength training session.

Study design: Ride a bike, get a massage

That’s a slight over-simplification; the study design was just a bit more complex than that. The participants had two visits, a preliminary screening to determine their VO2max and take a resting muscle biopsy, then a second session where they exercised to exhaustion (approximately 70 min) on a bike. Immediately following the exercise they rested for ten minutes then each leg was randomly selected to either receive a massage (treatment) or to act as a non-treatment control. We then took muscle biopsies from each leg immediately following the massage and 2.5 hours later and performed various measures in the lab in an attempt to see whether massage influenced the response of muscle to endurance exercise.

Mechanotransduction, mitochondria & inflammation

Massage is a mechanical stimulus where the rhythmic pressure applied to muscle can act to stretch individual fibres and alter their activity. Many cells have the ability to take these mechanical stimuli and convert them to chemical signals, where proteins change their activity in order to produce adaptations within the cell, a process called mechanotransduction. Not surprisingly, the activity of two mechanically sensitive proteins (FAK, ERK1/2) were increased in muscle immediately following the massage as compared to the non-treated leg.

The mechanically sensitive FAK protein (seen above) can act to alter PGC-1α, that also increased its activity following massage. PGC-1α is a ‘transcriptional co-activator’, a fancy way of saying it helps other proteins to turn genes on. It’s best known for for it’s role in the creation of new mitochondria within the cell (mitochondrial biogenesis) and sure enough with altered PGC-1α came increased expression of mitochondrial genes. This was certainly an exciting finding, but to keep things in perspective, this was only during the first 2.5hrs following exercise, so the creation of new mitochondria wasn’t observed directly, just signs that suggest it could happen down the road.

But the results don’t stop there with the mitochondria. NFκB is an important protein that responds to cell stress and regulates the production of other proteins in the inflammatory response, specifically inflammatory cytokines. Massage reduced the activity of NFκB which resulted in decreased interleukin-6 (IL-6, a cytokine) at 2.5 hours after the massage. Inflammatory cytokines have various roles but have been shown to increase muscle protein breakdown (2), reduce synthesis of certain muscle proteins (3), and cause increased sensitivity to pain (hyperalgesia, 4).

It’s important to note that while we can attribute some nasty functions to these inflammatory cytokines, they also have important physiological functions that are essential to the adaptive response to exercise. As one example, on top of all those ‘nasty’ functions above, IL-6 can activate satellite cells (5), which are known to contribute to hypertrophy following strength training. ‘Knock out’ satellite cells and you seriously limit hypertrophy (6). The crossover of these potential ‘good’ and ‘bad’ functions makes it difficult to interpret whether or not reduced inflammation following muscle-damaging exercise is always such a good thing.

What massage didn’t do

It is often said that massage increases bloodflow to muscles with the potential to improve the clearance of metabolic byproducts within muscle (lactate), and increase the resynthesis of energetic stores within the muscle (glycogen). Blood flow wasn’t assessed in this study, however previous work has shown no effect or even a reduction in blood flow with massage (7,8). In this study, massage didn’t increase muscle glycogen or reduce post-exercise muscle lactate concentrations more than controls, so it seems that the effects may be produced by the pathways discussed above, and not through the traditional theories involving bloodflow and muscle metabolites. Seems that the metabolite and ‘toxin’ theory of massage may be falling out of the spotlight.

I’m out-numbered by runners

Some have raised the question, given my obvious bias towards barbells, why we didn’t we use strength training?

Both the main author (Justin Crane) and lead investigator Dr Mark Tarnopolsky (our boss) are endurance athletes, and have frequently seen the use of massage with training. It’s definitely commonplace to see massage tents and tables surrounding the finish line of major endurance races. That’s not to say that weight-lifters, powerlifters and bodybuilders don’t do the same, but it’s likely that the population of runners is larger than those three groups combined, and probably more of them mix massage and exercise as a whole.

If I had my way, it would’ve been strength training (or both) but what can you do? It’s also important to note that the exhaustive exercise in this study did result in damage to the muscle, similar to what would be expected following a standard weight-training session, so there could be some parallels between the two exercise modes.

What we know about strength training and massage

There isn’t a significant amount of literature out there looking at the use of massage as a recovery technique from strength training, especially when looking for invasive investigations using muscle biopsies. Add in confounding variables like study design, types of massage, length of massage, timing after the exercise session, and you’ll leave with the idea that it’s difficult to really conclude anything at all. That won’t stop me from trying though.

What does exist suggests that massage can reduce the pain (delayed onset muscle soreness, DOMS) associated with strength training or intense eccentric protocols (9-13). Unfortunately reduced DOMS doesn’t necessarily reflect the underlying changes to muscle, so it can be difficult to associate reduced pain with increased muscle recovery and ultimately muscle performance.

Two studies have demonstrated reduced creatine kinase (CK) in the serum of participants who have undergone massage following intense eccentric contractions (10,13). It is fairly accepted that when muscle undergoes repeated eccentric contractions, damage to the muscle membrane causes the release of the enzyme CK into the circulation, and this can be used as an indirect marker of damage to the muscle. In the context of massage, the reduced CK response was associated with an elevated number of neutrophils in the blood, cells that normally infiltrate damaged muscle to participate in the removal of damaged tissue. This may seem counterintuitive, but it was suggested by the authors that the increased circulating neutrophils with massage represented a ‘blocking’ effect, where as many neutrophils don’t infiltrate the target tissue as would be seen without post-exercise massage. The smaller intramuscular neutrophil response could be associated with less collateral muscle damage and may be seen as reduced CK leakage from the muscle.

After looking at this, maybe the effects of massage in these intense experiments is not to facilitate recovery directly, but actually to mitigate the collateral damage that can occur following an overly-zealous immune response to exercise-induced muscle damage?

What’s changed after this study?

In reality, nothing concrete because we didn’t assess the response to strength training, just exhaustive endurance exercise. Nevertheless, we can theorize and make some useful extrapolations based on this data, and I think that we’d find a complementary result following strength training. Let’s establish the parallels between the three main responses we saw following the endurance exercise and massage study:

1. Mechanotransduction: It’s no surprise that some of these ‘mechano-sensitive’ proteins described above are altered by strength training, although they’re differentially affected based on exercise intensity (14). The activity of these proteins (specifically ERK1/2) is thought to decline as the intensity of training increases (>90%1RM) and volume decreases. Given this volume sensitive response, could post-exercise massage augment mechanosensitive signalling pathways to a greater extent following very high resistance (>90%1RM), where activation of proteins like ERK1/2 doesn’t occur or isn’t as high?
2. PGC-1α response: Traditionally we haven’t normally associated a mitochondrial response with strength training, however recent evidence suggests there is a mitochondrial benefit to strength training in specific conditions (15-17). A few groups have shown PGC-1α to increase following a strength training session (18,19), however it’s also possible that PGC-1α can function outside of the better known metabolic and mitochondrial pathways (20), so the significance of this response is unknown.
3. NFκB activation: Just like following exhaustive endurance exercise, NFκB protein levels increase in muscle following strength training (21). Since NFκB can modulate IL-6 (22) that we know is increased following resistance exercise (23) and involved in satellite cell activation (5) (cells that are essential for hypertrophy (6)), I’d certainly be interested to see how this would play out!

It’s obviously too soon to say that massage could enhance the response of PGC-1α to strength training or reduce NFκB and the inflammatory response to strength training, but based on the results of this current study with endurance exercise I’d say it’s definitely in the realm of possibilities.

Could the reduced CK release seen in (10,13) be related to a decreased inflammatory response? Can reduced NFκB, and ultimately IL-6 be related to the reduced DOMS that has been consistently observed after massage? What about neutrophil infiltration post-strength training, is it reduced or increased? I could go on here, but I think the point has probably been made by now.

At this point, it’s clearly too early to say, but there’s definitely a theoretical argument between the results of this current endurance-based study, the functional effects seen following strength training and eccentric damage, and the theoretical points I’ve thrown out there today. Certainly possible, but a big ‘if’ at this point. It’s also possible that any effects, whether positive or negative, could occur through entirely different mechanisms than what has been shown here with endurance exercise.

The jury is still out

This is a good start for the integrative study of massage and exercise, but it’s just that, a start. Much more research will be needed to determine optimal protocols, and whether the effects we found here with endurance exercise will be beneficial for those of the weight-training persuasion. We need longer-term studies to determine if the results we found here, namely the POTENTIAL for increased mitochondrial biogenesis actually manifests when the two are combined on a regular basis (training).

I’ll be back next week answering another important question I’ve received based on this study, whether or not we’d expect a similar effect if we used self-massage (foam rolling) instead of a therapist administered technique.