In rats, sore muscles after unusual exercise seem to start with a specific pain signal (called bradykinin) turning on right when the exercise happens. If you block that signal before exercise, the rats don’t get sore — but only if you block it early.

In rats with muscle soreness after exercise, two brain-chemical pathways team up to make muscles extra sensitive to pain, especially when certain pain-related proteins are present at low levels — and they both work through specific pain sensors in the nerves.

When rats do certain muscle exercises, they get sore deep in their muscles—not on the skin—starting a day later, peaking after 2–3 days, and going away by day 4. This soreness is due to increased sensitivity in the muscles themselves.

In rats, sore muscles after unusual exercise make a protein called NGF, which seems to cause pain sensitivity—blocking NGF quickly reduces soreness, and stopping another pain-related signal (bradykinin) also stops NGF from being made, suggesting it's part of the soreness chain reaction.