Dora Jackson RMT

Why does manual therapy work? An increasing amount of evidence points to systemic rather than local effects. Why does it matter? We need to keep it real so as not to perpetuate myth and reliably replicate results.

Why does manual therapy work?

It’s a question most of us have been asked — by patients, by students, sometimes by ourselves mid-treatment.

A 2025 living review in PLOS ONE (Keter et al.) pulled together 62 systematic, narrative, and scoping reviews to map the current evidence.

Manual therapy doesn’t act on one system. It produces measurable responses across the following:

- Neurological
- Neurovascular
- Neurotransmitter,
- Neuroimmune
- Neuromuscular
- Neuroendocrine
- Biomechanical

The strongest, most consistent signals are central, not local: increased pressure pain thresholds at sites distant from treatment and enhanced descending pain modulation.

The biomechanical “joint-out-of-place” model? It's not supported by the evidence. The treatments purporting to do this may help, but for the reasons above, not because the joint has been popped back in.

What this means in practice: our hands are interacting with the central nervous system at least as much as the tissue beneath them and the language we use with patients should reflect that.

The full one-page clinical summary is below 👇

📖 Source: Keter et al. (2025), PLOS ONE. doi:10.1371/journal.pone.0319586

“One size fits all” has never really worked. All generalizations are doomed to inaccuracy and ineffectiveness at least some of the time and any measure of success is likely due to luck. Research that targets specific populations can only help us find better solutions to pain and disease.

For decades, the assumption has lingered that women must tolerate pain better than men. After all, women experience childbirth, menstrual cramps, and other painful conditions throughout their lives. But research tells a different story — one that has profound implications for how we understand and treat pain.

Stanford’s Dr. Sean Mackey has been at the forefront of challenging these myths. “These studies are sending us a clear message that s*x differences aren’t just stronger or weaker — they’re often entirely different wiring diagrams,” he explains in a recent Washington Post article. “And we need to be mindful of these differences between men and women when we’re treating them.”

Those differences are more than theoretical. Scientists now know that everything from brain circuitry to immune pathways to pain-sensing neurons can function differently depending on s*x. These biological distinctions explain why certain conditions — like migraine, fibromyalgia, and irritable bowel syndrome — disproportionately affect women, and why treatments may succeed in one group but not the other.

Take migraine drugs that block CGRP, for example. They were initially tested in male rodents, leading researchers to believe the therapy wasn’t effective. When the studies were expanded to include females, the opposite was revealed: the drugs had little effect in men but transformed care for many women. Without s*x-specific research, that breakthrough might never have reached patients.

For Mackey, the lesson is clear: progress in pain medicine depends on listening to patients, respecting their differences, and designing studies and treatments that reflect the diversity of human biology. And while he is known for advancing the science, his message to people living with chronic pain is just as direct: “Don’t suffer in silence, and don’t give up. There is help out there.”