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Sporty rats beat sedentary rats paws down



The 2024 Global Year will examine what is known about sex and gender differences in pain perception and modulation and address sex-and gender-related disparities in both the research and treatment of pain.

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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


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