Most of the musculoskeletal treatments we use help many patients, yet we still cannot say with confidence how they help — and that is not a reason to doubt them.

The question every clinician hears

Sooner or later, every patient asks it: why will these exercises fix my knee? Why does pressing on my back ease the pain? The literary critic Northrop Frye once observed that “the simplest questions are the hardest to answer,” and “why?” may be the hardest question in a physiotherapy clinic.

We reach for tidy answers. “You need to strengthen the muscles around the joint.” “That technique unlocked a stiff segment.” These explanations are easy to say and easy to understand. The trouble is that current evidence does not support them as the reason patients feel better.

The puzzle runs the other way too. Two patients with near-identical presentations get the same programme; one improves, one does not. Others improve with interventions whose working process nobody can describe. In a recent JOSPT editorial, Chad Cook and Damian Keter argue that this uncertainty is not a failure of the field. It is what we should expect when treating complex, living systems.

What we mean by a “treatment mechanism”

A treatment mechanism is the process — molecular, cellular, or whole-body — that explains why a patient changes after an intervention. It is the “because” behind the outcome.

The awkward finding is that even when researchers do identify a mechanism, it usually explains only a small slice of the improvement patients report. This gap shows up almost everywhere we look:

• Strengthening exercise — in patellofemoral pain, gains in hip strength account for surprisingly little of the pain relief from hip exercise.
• Manual therapy — a living review of the literature finds many plausible pathways but no single one that accounts for clinical results.
• Medication — even paracetamol, one of the most widely used drugs in the world, still lacks a fully settled mechanism.
• Psychologically informed care — for approaches such as cognitive behavioural therapy, the proposed mediators explain only part of the benefit.

The lesson for clinicians: seeing improvement and understanding improvement are two different things, and we routinely have the first without the second.

Why mechanistic research is still worth doing

None of this makes the search pointless. Understanding mechanisms is how we move toward more precise, individualised and genuinely new treatments. The limitation is where much of that work happens: animal and preclinical models that isolate one pathway under tight control. Those studies are rigorous, but they show only a narrow slice of how a real person recovers. Human biology does not run in neat, one-step sequences, and studying one mechanism at a time can miss the connected processes that drive outcomes.

Why certainty keeps slipping away

Musculoskeletal pain is not one thing happening in one place. It sits where tissue physiology, pain neuroscience, psychology and social context meet, and these domains constantly influence one another.

Our treatments behave the same way. A single exercise session may load tissue, change how the nervous system processes threat, shift a patient’s beliefs about movement, and build confidence through the therapeutic relationship — all at once. These effects can reinforce, amplify or cancel each other, and some of them may never be directly measurable.

The inverse relationship

This leads to what Cook and Keter describe as an inverse relationship between how easy a mechanism is to study and how much it tells us about real clinical care:

• Easy to study, limited clinical value — a single cellular or tissue pathway in a controlled lab model.
• Harder to study, more clinical value — interactions across body systems in human participants.
• Hardest to study, most clinical value — the whole person recovering in the real world, where biological, psychological and social processes all play out together.

Reductionist explanations are appealing because they are clear. But clarity bought by ignoring most of the system risks oversimplifying a recovery process that is multifactorial and constantly changing.

What this means in the clinic

Uncertainty about mechanisms does not mean a treatment lacks value. It means we should be honest about what we know and careful about what we claim.

Explaining treatment without overclaiming

Patients deserve a rationale, but not a false one. Swap single-cause stories for explanations that are true and still reassuring:

Instead of saying…	Try something like…
“Your back is out; I’ll put it back in.”	“Hands-on treatment often calms a sensitive back and makes moving easier. That gives us a window to get you active again.”
“These exercises will fix your weak muscles.”	“Regular, gradually harder exercise helps most people with this problem. It works through several routes — tissue, nerves, and confidence — not just strength.”
“This will definitely work.”	“This approach helps many people with a problem like yours. We’ll track how you respond and adjust if needed.”

Making sense of variable responses

When similar patients respond differently, that is the expected result of many interacting factors — not proof the treatment failed or the patient did something wrong. Measure outcomes that matter to the patient, review progress early, and adapt rather than doubling down on a single theory.

Stepping out of binary debates

Public arguments about whether a treatment “works” or “doesn’t work” rarely help anyone. Accepting complexity lets clinicians discuss probabilities, trade-offs and individual responses — a more accurate and more respectful conversation with patients.

Staying clear of pseudoscience

The gap between “we see it help” and “we know why” is exactly where pseudoscientific claims creep in. Resist filling the gap with confident but untested explanations. “We don’t fully know, but here’s what the evidence shows” is a strong clinical answer.

The bottom line

We may never fully map how musculoskeletal treatments produce their effects. Accepting that is not giving up — it frees clinicians and researchers to focus on the questions that matter most and the methods able to answer them.

• Improvement is real even when its mechanism is unclear.
• Simple mechanistic stories (“strength,” “unlocking”) are rarely the full explanation.
• Recovery emerges from biology, psychology and social context acting together.
• Variable responses are expected; monitor and adapt.
• Give patients honest, evidence-based rationales rather than tidy myths.

Source

Cook CE, Keter DL. Musculoskeletal treatment mechanisms: a puzzle that may never be fully solved. J Orthop Sports Phys Ther. 2026;56(9):569–570. doi:10.2519/jospt.2026.14486

This article is an independent summary and interpretation for clinicians; see the original editorial and its references for full detail.