Sporty rats beat sedentary rats paws down

When we ask whether something in medicine is validated by science, the basic approach is to demonstrate biological plausibility (basic science research) as well as actual real-world efficacy (public health research). In other words, it is more interesting when something that works is actually supported by known biological mechanisms. We feel that conclusions based on such evidence are much more probable and, ultimately, intellectually satisfying. So is there any evidence that might support the idea that staying active following injury is good for you?  Mind you, I am not looking for any obvious things like the potential effects of movement on fear or mood; I am specifically on the hunt for something at least slightly “esoteric”!

Thus, I came across two studies that tested whether exercise is associated with real “clinical” differences and demonstrable biological responses following (1) nerve injury and (2) immune challenge. Both teams measured the levels of cytokines and Heat Shock Protein 72 (Hsp72). Cytokines are the small signalling proteins that help coordinate the inflammatory response (among other things). Hsp72 appears to be released during cellular stress and, amongst other things, can prevent cell death (apoptosis) by cytokines like TNF-alpha.

Nickerson et al looked at the cytokine IL-1β and Hsp72 levels following administration of the bacteria Escherichia coli. They asked 36 rats to participate (and I can only assume that they consented by placing their paw marks on consent forms following a careful interrogation of the study information sheets). Nicely, they included a small rat control group who only received saline (without the bacteria) just in case those clever rats clued on to the hypothesis and which condition they had been assigned in the study. The investigators found that physically active animals carried less evidence of the bacterial challenge in their blood suggesting that they cleared the “infection” faster than the “office-bound” rats. In addition they found that the levels of cytokines and Hsp72 were more desirable in the active rats.

Chen et al, on the other hand, looked at the levels of two pro-algesic cytokines (TNF-α and IL-1β) as well as Hsp72 in rats whose sciatic nerve had been experimentally damaged. Again, this study used control sham surgical groups to prevent bias and even used a blinded investigator to assess pain (rat pain behaviour requires fairly subjective interpretation). In this study, it was found that rats who engaged in treadmill walking and swimming exhibited reduced pain behaviour and expressed less of the cytokines IL-1β and TNF-α and increased levels of Hsp72; all desirable effects. I believe that the investigators also tried having a cycling group with the ultimate aim of starting a rat triathlon team but the rats kept messing up the gear changes.

In conclusion, both studies demonstrated that exercised rodents appear to respond better to their respective medical problems than their sedentary friends. Of course, the precise mechanisms of the relationship between exercise and pain are very much more complex than its effect on the immune response. Once we start to look at people, this complexity is arguably increased. However, when seeking evidence of the potential biological plausibility of a management approach, it is helpful to see that there is some evidence out there that can be used to build a case.

Given the complexity of the immune response and of people, I can only end by saying that biological plausibility becomes clinically meaningful when backed up by evidence of efficacy from properly controlled clinical trials. That’s a story for another day.

Luke Parkitny

Luke Parkitny Body in MindLuke Parkitny is a PhD student at Neuroscience Research Australia. He is researching some of the factors that play a role in the development of complex regional pain syndrome (CRPS). Luke joins the Body in Mind team with a background of clinical practice and research in Western Australia. He has rapidly cultivated an interest in all things pain and has very successfully exploited every opportunity to share this knowledge with other health professionals and lay-persons. Link to Luke’s published research and here he is in person talking about what he does.


Nickerson M, Elphick GF, Campisi J, Greenwood BN, & Fleshner M (2005). Physical activity alters the brain Hsp72 and IL-1beta responses to peripheral E. coli challenge. AJP. Regu physiol, 289 (6) PMID: 16081876

Chen YW, Li YT, Chen YC, Li ZY, & Hung CH (2012). Exercise training attenuates neuropathic pain and cytokine expression after chronic constriction injury of rat sciatic nerve. Anesthesia and analgesia, 114 (6), 1330-7 PMID: 22415536



  1. Luke Parkitny says


    Thank you for your comment.

    I think language (names and definitions) are immensely important in guiding understanding and our paradigms. As a rule, I always try to look at the big picture and common elements in the body; thus, personally, I am always very resistant to giving specific local names to factors that are biologically equivalent to other factors. One of the beautiful things about calling a cytokine a cytokine (as an example) is that we start to immediately see the wide ranging activity of that factor. Calling it a myokine starts to make it look like it is somehow qualitatively different depending on the site of release. It is an interesting idea and am glad you brought my attention to it and I do see that there is some merit to the argument made in that paper. However i also strongly feel that when we move away from our individual specific interest areas and start to see the common threads we will start to truly approach a recognition of the systemic viewpoint. This, for me at least, is when the science starts to make sense.

  2. Stephen Jeffrey says

    Don’t forget your myokines =

    Professor Bente Klarlund Pederson has been doing this research for more than 10 yrs.
    Myokines may not, yet, make it as a known biological mechanism but being a massage therapist I LOVE this idea. 🙂

  3. Luke Parkitny says

    Thanks Elise. I hope that the Monday has treated you well.

  4. Luke Parkitny says

    Dear Deano and Neil;

    All great points and well picked up on the interpretation. I find that it is always difficult to write about the outcomes of basic science research without adding several disclaimers as to its potential meaning. I tend to look at these types of studies as pieces of a jigsaw puzzle; we put them together and start to see a brick wall forming but we still ultimately can’t work out if the picture is of Westminster Abbey or of a structurally sound outhouse.

    While the physiological responses exhibited by lab rats might reflect what happens in humans, their real-world relevance to human life is not so easily ascertained. In reality, the real purpose of these mechanism-based studies is to provide some scientific plausibility to existing arguments and, where warranted, to lead to and support further research in humans. Without those other pieces of the puzzle we might just end up cherry-picking our evidence and build an abbey out of a toilet. Of course, that doesn’t make the findings any less exciting when you’re trying to make sense of something that is ultimately very complex.

  5. Thanks for the interesting start to a Monday morning at work Luke! I also saw your CRPS workshop at the NOI conference this year and thought it was really informing and interesting. Some of the patients I come across are CRPS patients and appreciate all the help I can get in treating them! Good luck with your PhD.

  6. That’s an awesome post Luke. It is excellent to have a plausible rationale for our recommendations, and it seems we now h ave that for first episode of neuropathy.
    I always worry about people using this information to support agendas other that patient best-interest.
    Now we need to do a study in which we reinjure the little fellows just as their pain behaviors are starting to resolve. This would show if we have the same evidence to recommend exercise in those with recurrent injury.
    We could also try the same experiment but add a stressor between the exercises.
    We could also try the same experiment but force them to be active in a way that increases pain behaviors during and after the exercise, to see if how much it hurts during exercise matters.
    And of course, we could have some fun and see if rats get the same response from yoga as from marathon training.
    One other thought just came up as I re-read the blog title … Would the results be different if we started with rats who were sedentary versus ones who are normally active?

  7. Cheers Luke – please forgive me for not being a big fan of the reductionist approach but this will certainly be a useful addition to convince some of my more intellectually responsive patients to continue to move (FLOW (Functional Longevity Optimal Wellness ) by Coomer).