How to best assess pain-related behaviors in preclinical studies
Most humans can tell you they’re in pain. However, assessing pain sensitivity in rodents during preclinical studies is a challenge.
Read More arrow_forwardSo what can one footprint tell you? Well, it could tell you a lot. There are sophisticated ways of footprint analysis.
So here it is – the first blog in a series of three, about rodent gait analysis and what a single footprint can tell us.
So what can one footprint tell you? Well, it could tell you a lot. Simply putting the paw in ink and studying the print left behind is one way to go about it, but there are far more sophisticated ways of footprint analysis. While an ink-print can give you an idea of the print area of a foot, you cannot tell how the animal is distributing his weight across its feet. It also cannot tell you the maximum surface area of a foot touching the ground during the duration of the entire footfall. Modern systems can.
Modern systems that use light to detect a footfall can indicate the intensity of a print, which in turn can correlate with how the animal is bearing its weight. In models of conditions that affect a single limb, the animal often shows less use of the affected paw. This is reflected in a relatively lower intensity of that footprint, which is found in models of arthritis [8,9] and sciatic nerve injury [1,2,4,10].
Maximum contact area and total print area are two different things that cannot be distinguished using a regular ink print. The total print area is the accumulated picture of the entire time the paw came in contact with the ground. It is what would be left behind if you had dipped that foot in ink. But cleaner. The maximum contact area is the area of the foot touching the plate during the time of maximum contact, which is usually smaller than the total print area.
Similar to the changes found in print intensity, a smaller contact area also reflects altered use of the affected limb. Again, in literature this is described in models of arthritis [8,9] and sciatic nerve injury [1,2,4,10]. Other disorders that show one or more affected paws, also show a clear reduction of print and/or contact area, such as models of ischemic stroke [5,7].
On the other hand, research on spinal cord injury reports an increased print and contact area for all four paws in a contusion injury model of spinal cord injury, and a less dramatic but still significant effect in the hind paw print areas in a dorsal cord transection model of spinal cord injury [6].
The shape of the paw, the length, and how the toes are spread, are important in research on nerve injury, arthritis and pain. These can cause deformation of the feet, altering the parts of the sole that make contact with the ground [1,2,3,4].
The sciatic nerve is a long nerve that originates in the lower back and runs down through the limbs. It branches of in the tibial and the peroneal (also called fibular) nerve. Injury to these nerves in rodents are often used as a model to study nerve regeneration, using print length, toe spread, paw angle and other gait parameters as a behavioral endpoint to measure functional recovery.
Nerve injury can cause "clawing" of the feet. In sciatic [3] or tibial nerve injury, this is often reflected in a longer print but a decreased toe spread, while damage to the peroneal nerve often results in a shorter print with a diminished toe spread. These characteristics are represented in nerve specific indexes; the sciatic functional index (SFI), the tibial functional index (TFI), and the peroneal functional index (PFI). Based on print length (PL), toe spread (TS) and intermediate toe spread (ITS), these are automatically calculated by gait analysis systems.
We can again find the advantage of using modern technology over ink dipping; the more accurate the print is (in other words: no ink smudges), the more accurate these indexes are.
Paw angle is the angle between the paw axis and the body axis or between the paw axis and the direction of movement (the vector). This angle can be affected by abnormalities of the muscles responsible for the placement of the paw, the nerves that innervate these muscles, or even deformation of the bones and joints of the leg belonging to the paw. Changes in paw angle are seen in models of arthritis, ataxia, stroke, and spinal cord injury.
All the parameters and indexes mentioned in this blog can automatically be detected, measured, and calculated with gait analysis systems such as CatWalk XT. Now imagine adding inter-paw parameters such as the distance between paws, or the length of a stride. And what if you added time to your analysis? Stay tuned for the other blogs in this series…
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References
Most humans can tell you they’re in pain. However, assessing pain sensitivity in rodents during preclinical studies is a challenge.
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CatWalk XT provides the opportunity to study a variety of gait parameters. But, which parameters should you use for your mouse model? Read this blog to learn more!
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The usefulness of gait is well established in research on spinal cord injury, ataxia, and arthritis. But in fact, research on all disorders that influence gait in any way, can benefit from gait and footfall analysis.
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