We use animal models such as mice, rats and others to help us understand pain mechanisms and extrapolate the results to learn more about human diseases. In humans, when the pain lasts more than three months, we regard it as being chronic. Considering the relative lifespans of humans versus mice, three months of life in humans is approximately three days in mice. However, there is no reason to believe that the speed in which chronic pain mechanisms develop over time is different in humans and in mice. Therefore, three months of pain in humans may be the same as three months of pain in mice. The vast majority of animal studies test pain for four weeks or less after the injury that causes it. Thus, it seems that actual long-term pain has rarely been studied in mice or rats.
Goal
Chronic pain can be a major cause of stress and it has been previously shown that stress has an effect on mortality in both humans and mice. Researchers at McGill University wanted to evaluate whether nerve injury or pain developed following the injury can affect lifespan in mice by testing mice throughout their life.
Methodology
To test this, some mice received a partial injury to the nerves going to and from the foot (SNI injury), the same kind of injury that can cause neuropathic pain in humans. Some mice received a sham injury where they were anesthetised and their nerve was exposed but not injured. Before the surgery and every three months until their death, the mice were weighed and tested on different pain sensitivity tests, and for guarding behavior and frailty. Both male and female mice were tested.
Mechanical sensitivity was tested with the Von Frey test. This test consists of touching the mouse’s hind paw with calibrated plastic filaments of different diameters until the hind paw is withdrawn. If they experience more pain, mice will withdraw their hind paw when touched by the smaller (i.e., lighter) filaments.
Cold sensitivity was tested with the acetone drop test, where the experimenter applies a drop of acetone on the hind paw, which quickly evaporates, cooling the skin. Over the next minute, the time that the mouse spends attending to (i.e. sniffing, licking, and shaking) its hind paw is measured; more behaviours indicate higher levels of cold pain.
Guarding behavior and frailty were observed and scored with standardised scales.
Main findings
The behavioural tests showed that male mice displayed stable and continuous pain after injury throughout their life. The female mice, however, experienced pain until somewhere between 3-6 months after surgery, pain which disappeared completely and then completely returned at 12-15 months post-surgery. There was no evidence that the SNI injury decreased lifespan or frailty in either sex. But in male mice only, the pain itself had an effect on mortality, such that male mice died sooner if they had more pain and lived longer if they had less pain.
Take home message
It’s not the injury itself that has an impact on mortality, but the chronic pain and its consequences that follow post-injury. The effects are specific to male mice, suggesting that females might be resistant to some negative consequences of pain.
