As long as I’m stranded in a snowstorm (thankfully fading right now) and unable to teach my human physiology class this morning, I thought I’d at least put a small part of the story I was going to tell on the web. We’re currently talking about muscle physiology, and I’ve already gone over the sliding filament theory of muscle contraction…oh, you know that one, right?

Muscles contract using interlaced filaments of myosin (in red, above) and actin (blue), and myosin acts as a kind of motor gear, burning ATP to ratchet the actin filaments along their length, shortening the muscle. The ratchet functions whenever the cell has ATP and also is flushed with the release of calcium from internal stores, which is the chemical trigger to initiate a contraction. But you knew that already.

You also knew about basic metabolic biochemistry, the process that breaks down sugars to release energy, which is captured in the form of ATP and various reducing agents.

All you need to remember to follow along is that there is the glycolytic pathway, which snaps a 6-carbon sugar in half to produce two 3-carbon fragments and a little bit of energy, and that there is the rest of the biochemistry shown here, which takes the 3-carbon fragments and burns them down the rest of the way to CO₂, producing a lot of energy in the form of ATP. Unfortunately, that second, very efficient part is dependent on the availability of oxygen, so in many cases, where your muscles are working harder than the respiratory/circulatory system can deliver oxygen to them, they are only doing the glycolytic part of the process.

Like I said, though, you already knew all that. I was planning a quick review of these basics this morning, and to discuss factors that influence strength and endurance in muscle activity, and then to answer the one question I’m addressing here: why do my muscles hurt after exercising?

There are actually a couple of reasons. One that you may have heard of before is lactic acid buildup, but this is actually only a short term concern. Lactic acid is a byproduct of glycolysis. If you’re working hard, you can’t deliver oxygen to the muscles as fast as they need it, so they rely almost entirely on the glycolytic pathway for energy, which in my diagram above has three products: ATP (which the cell wants to use for contractions), and pyruvic acid and the reducing agent NADH₂, which the cell is unable to use at that time because of the lack of oxygen. What the cell does to keep the unusable products from accumulating and bringing the glycolytic pathway to a halt is, in short, to use the reducing agent to convert pyruvic to lactate, which then diffuses away into the bloodstream. Later, when you’re taking it easy and recovering from your workout, the lactate will be recovered and reprocessed to recover more ATP and also to rebuild some of the glucose that was burned.

(Scratch much of the above paragraph. While many physiology textbooks state that lactic acid accumulation is a problem, the biochemists say otherwise: what builds up is lactate, which doesn’t acidify the tissues and can actually act as a buffer. The source of acids that cause the transient ache are the hydrolysis reactions that occur as ATP is used at a rapid rate.)

Anyway, the point here is that one source of that burning ache during exercise is lactic acid accumulation. This does not explain why it hurts the next morning when you get up, though, because the acid will have been cleaned up by then. That’s a different problem.

One reason for stiffness and soreness is the long term effect of flushing the muscle cell with calcium. During exercise, each contraction is accompanied by a surge of calcium ions, followed by its removal by pumps in the sarcoplasmic reticulum slurping it back up for storage. So exercise consists of a repeated cycle of surge and slurp of calcium ions, and one of the effects is that the increased levels of ions lead to actual physical swelling of the muscle fibers, which can reduce short-term performance. Another effect is that altering the calcium balance of the cell leads to the activation of enzymes that break down and rebuild proteins in the cell. What that does is promote active remodeling of those actin/myosin filaments, construction of new filaments, and growth of the muscle. It hurts because the muscle is under construction and is being physically remodeled, just like your coach probably told you. No pain, no gain.

There’s another reason muscles may hurt a great deal the day after exercise, and that is that you can actually disrupt and damage and even kill muscle fibers, and that certain kinds of exercise are particularly effective at damaging the tissue.

A couple of years ago, I had this brought home personally. Our students have to give a senior seminar in a biology topic of their choice in their last year, before we let them graduate, and one of my students was interested in exercise physiology and knew about this phenomenon of eccentric exercise promoting greater tissue damage. He also knew that it had its most potent effects in naive tissue — muscles can adapt to repeated abuse, and show smaller and smaller responses to this kind of exercise over time. He was an athlete, so it was going to have minimal effect on him, so he looked about for a flabby, lazy, deskbound sort of person to test, and somehow he thought his advisor, me, would be a perfect subject.

Concentric and eccentric exercise are different. Imagine holding a weight in your hand as you sit there, and you contract your biceps to bend your elbow and lift the weight towards your face — imagine drinking a large stein of beer, for instance (it’s exercise, really). The muscle filaments are ratcheting along to contract, and they are shortening the muscle: that is concentric exercise. Now, though, you lower your hand to put the stein back on the table. You don’t simply relax all your muscles and let your arm flop so the stein falls with a crash to the table — it might spill! — instead, the muscle fibers in your biceps are at a low level of activity, the myosin/actin filaments are ratcheting to generate tension, while the muscle is lengthening, rather than shortening. That’s eccentric exercise: some of your muscle fibers are trying to shorten the muscle while the muscle is actually lengthening.

So my student took me to the gym for a relatively easy hour of working out in the weight room, concentrating on eccentric exercise. It wasn’t bad at all, and he kept the workout relatively light, so I never strained myself. So we did things like assisted bench presses, where he would help me raise the weight (the concentric part), and then I would ease it down slowly (the eccentric part). It wasn’t bad at all, I thought, and we did a series of simple exercise to work out different muscle groups.

Then, the next morning, I tried to get up. Aaaaiaiaiaeeeaaargh. His experiment had been spectacularly successful, and I could barely move. Let me tell you, brushing my teeth that day was the most exquisite agony — just raising my hand to my mouth was bad enough, but wiggling my arm gently once I got it there? Forget about it.

So I got to be a prop at his seminar, standing still at the front of the room and occasionally screaming through gritted teeth when he asked me to move in certain ways, while he explained what was going on in my muscles. I had to give him an A for admiration at his fabulously sadomasochistic technique.

So what had I done to my muscles? Forced lengthening of muscles under tension actually causes small tears in the fibers, disrupting the excitation-contraction coupling mechanism. There are tiny membranous tubes running through the muscle fibers called the t-tubule system, which conducts electrical activity at the membrane deep into the interior, where it activates the sarcoplasmic reticulum to release calcium. Those were being torn. That makes the membrane leaky and sensitive, leading to fluid imbalances, and generally making the muscle less responsive until repaired.

Another factor is damage to the filament structure. The peculiar extension while contracting would lead to errors in the alignment of the overlapping parts of the myosin and actin filaments, leading to tangled, disrupted structures that are no longer able to function efficiently, and further contraction could cause physical injury to the fiber, which triggers a pain and inflammation response.

During an active lengthening, longer, weaker sarcomeres are stretched onto the descending limb of their length-tension relation where they lengthen rapidly, uncontrollably, until they are beyond myofilament overlap and tension in passive structures has halted further lengthening. Repeated overextension of sarcomeres leads to their disruption. Muscle fibres with disrupted sarcomeres in series with still-functioning sarcomeres show a shift in optimum length for tension in the direction of longer muscle lengths. When the region of disruption is large enough it leads to membrane damage. This could be envisaged as a two-stage process, beginning with tearing of t-tubules. Any fall in tension at this point would be reversible with caffeine. It would be followed by damage to the sarcoplasmic reticulum, uncontrolled Ca2+ release from its stores and triggering of a local injury contracture. That, in turn, would raise muscle passive tension. If the damage was extensive enough, parts of the fibre, or the whole fibre, would die. This fall in tension would not be recoverable with caffeine. Breakdown products of dead and dying cells would lead to a local inflammatory response associated with tissue oedema and soreness.

This process actually messes up your muscles. These are electron micrographs of muscle biopsies taken from human subjects who’d been put through the procedure (I drew the line there, and did not let me student stab me with big needles — hadn’t he gotten enough pleasure out of this already — so these aren’t my muscles).

The control at the top left shows normal, healthy, well-organized muscle fibers; the panel just below it as a sample from muscle immediately after eccentric exercise, which is clearly more disorganized. The three panels labeled “1d” all show muscle one day after eccentric exercise, and all show signs of disruption — look at those z discs, the dark bands in the muscle. They’ve been broken up quite a bit.

If your muscles hurt, though, don’t panic: the panel at the top right is of muscle fibers 14 days after exercise, and they are fully recovered and are once again well-ordered.

So why do your muscles hurt after exercise? There are three major reasons. 1) a transient accumulation of acids produced by ATP hydrolysis that can cause some soreness during exercise. 2) Changes in ion concentrations in the muscle that can cause some fluid swelling, and also triggers active remodeling of the proteins for growth. And 3) you broke ’em. You can cause micro-tears and internal disruption of muscle proteins that can actually force your muscles to throw out and reconstruct whole fibers.

What should you do if your muscles are aching after exercise? Personally, I say just stop it altogether, but that’s just me. For the more active and sensible among you, a better solution would be to reduce the intensity of exercise to light, submaximal exertion and stretching exercises, which have been found to reduce soreness and promote more rapid recovery of muscle tension. Light massage is also good for reducing pain, but hasn’t been found to do much to facilitate actual physical recovery otherwise. I’m all for reducing pain, of course.

As usual, though, if pain worsens or continues for more than a few days, or is particularly intense and localized, get off the internet and SEE A REAL DOCTOR. In the case of my intentionally induced eccentric muscle exercise, the serious pain only lasted for about 3 days, and after a week, felt no after-effects at all.

Proske U, Morgan DL (2001) Muscle damage from eccentric exercise: mechanism, mechanical signs, adaptation, and clinical applications. J Physiol 537(2):333-345.