Trigger points debate greatly delayed (Member Post)

If only you’d thought of that great comeback when it counted, instead of 16 minutes later! Or … 16 years later?

Maybe it wasn’t worth the wait! This post is about a bizarrely late letter to a scientific journal about some old muscle knot evidence — which remains controversial.

Controversy about the common sore spots in muscle known as “trigger points” is entirely about how they work. We all agree that there is a clinical phenomenon that needs explaining, and we all argue about what the explanation is. (See my high-level overview.) In other words, the question isn’t whether they “exist,” but what exists?

In 2008, Shah et al. published particularly interesting evidence about the etiology of trigger points, reporting that they are acidic and sloppy with waste metabolites — which gave support to the controversial “tiny cramp” hypothesis of sore spots, but has never been replicated. It was easy for skeptics to dismiss it as “just one study, and an error-prone one at that” back then, but … did anyone write a strongly worded letter?

Sixteen years later, Albert Moraska and Robert Hickner have expressed their “concerns” in a letter to the journal. Science moves slowly. An exchange of words ensued, basically:

Moraska & Hickner — What you did was so technically tricky that the extraordinary results seem dodgy.

Shah et al. — Yes, science is hard. We acknowledged the limitations and the result was plausible.

Moraska & Hickner — Is not!

Their basic concern could apply to many famous scientific results that were ultimately replicated — and more that weren’t! It’s a legitimate point, but also mostly a moot one without more evidence. But here are some highlights for nerdy fun …

Probing the probe

Microdialysis is how we study the molecules in tissue fluid: insert a hollow needle probe filled with saline solution, and small molecules drift into it just like they would into a capillary … et voila, “just” measure what comes out. It gets technical! And Shah et al. had to push the technology forward.

M & H called it a “self-fabricated” probe, implying amateurishness, like they imagined Shah et al. hunched over a kitchen table with glue sticks and duct tape.

Shah et al. objected rather tartly: “This implies the needles were homemade.” In fact, the probe was built by a “highly skilled engineering staff in a technical laboratory,” and the system “underwent a comprehensive review by microdialysis experts selected by the journal.”

M & H had no follow-up on that.

Half of science is upgrading tools.

By Facaccia, CC BY-SA 3.0, via Wikimedia Commons

Some microdialysis probes.

The acid, it burns!

pH is a measure of how acidic or alkaline a substance is, on a weird scale from 0 to 14, with neutrality in the middle at 7. It's also an exponential scale, like the Richter scale. Shah et al. reported pH in the same ballpark as coffee and beer, which sounds tame … but that’s crazy for muscle tissue, and M & H just can’t believe it:

“The reported muscle pH of 4.2 within an active TrP is unlikely as it would cause permanent cellular protein damage.”

But why would protein damage break plausibility here? It does make the claim somewhat more "extraordinary," but we are talking about investigating a pathology, after all: you’re looking for trouble, and hoping for informative surprises.

“Who is to say that there is not protein tissue damage associated with trigger points?” Shah et al. write. "A lower pH is not only quite possible, but to be expected, especially if the normally protective buffering mechanisms are disrupted." They make several other points in principle and in detail, a full page about this one concern!

• low pH has been noted by others
• there are known cellular sensors for very low pH (implying it's not an entirely exotic biological situation)
• the pH they measured wasn't necessarily limited to muscle
• there is evidence of denatured proteins in stressed muscle

The rebuttal from M & H contains only a complaint that the citations are inadequate: "None of these references alter our skepticism."

Judgement: Shah et al. claim an unnecessary victory

I don’t think Moraska and Hickner are actually all that skeptical about trigger points in general, but they are certainly skeptical about these experiments. And I have no objection to the spirit of their call for “caution when referencing these studies” … but was it worth the wait? Better late than never? Or just late?

Just late, I think. The need for caution always seemed obvious to anyone who matters, and the only solution to the uncertainty is replication, replication, replication. Here is what I originally wrote about these experiments in the late 2000s, “cautious” from the start, even as a neophyte critical analyzer:

In a complicated and very technical experiment, it is all too easy for researchers to find the result that they want to find. This is why independent confirmation from other experiments is always essential. This research has still not been replicated as far as I know, and it has been criticized and dismissed by some.

So take it all with a grain of salt for now. Maybe effectively forever, at the pace this research moves.

And here we are now, sixteen years later, still waiting for replication. It’s like waiting for the last Game of Thrones novel!

M & H’s criticisms are reasonable in broad strokes, but I think they lean too heavily into “you just can’t trust these fancy techniques.” I prefer Shah et al.’s thoughtful and detailed contribution. So I give the debate win to them, and I’ll give them the last word too:

“These authors encourage the letter writers to collect data and perform controlled studies, using well designed methods and instruments to further investigations relevant to myofascial pain that test their hypotheses as suggested in their letter.”