Corticospinalexcitabilityasabiomarkerofmyofascialpainsyndrome

Myofascial pain syndrome (MPS) is one of the most common chronic pain disorders, yet it lacks clear, effective diagnostic criteria. Patients with MPS experience pain in muscles and connective tissues, often centered around myofascial trigger points—hyperirritable nodules in muscle fibers that can cause local and referred pain. The exact mechanisms behind MPS remain poorly understood, and clinicians currently rely heavily on subjective clinical assessments rather than objective biological markers. This gap in understanding has motivated researchers to explore whether measurable changes in brain function could serve as reliable biomarkers for the condition.

One promising area involves corticospinal excitability, which can be measured non-invasively using transcranial magnetic stimulation (TMS). In chronic pain conditions, the brain's motor cortex often shows altered activity, specifically a phenomenon called intracortical disinhibition—essentially, a failure of the brain's normal inhibitory processes that keep neural activity in check. This systematic review aimed to examine whether measurements of corticospinal excitability, particularly intracortical disinhibition, could serve as valid biomarkers for MPS.

The researchers conducted a systematic review of the scientific literature to identify clinical trials that investigated MPS and corticospinal excitability using TMS. They searched PubMed using specific terms related to myofascial pain syndrome and transcranial magnetic stimulation, checked reference lists of retrieved articles, contacted experts in the field, and reviewed neuromodulation meeting proceedings for unpublished work. They included studies involving patients with MPS that assessed cortical excitability measurements, and excluded articles not focused on MPS, those without cortical excitability data, reviews, and non-English articles. From 24 articles initially identified, only 4 studies met their inclusion criteria.

All 4 studies were conducted by the same research group. The researchers then applied the Bradford Hill criteria—a well-established framework for evaluating causal relationships in epidemiology—to assess whether the observed neurophysiological changes could be considered causally related to MPS. They also compared their findings on MPS with other chronic pain conditions including fibromyalgia, osteoarthritis, neuropathic pain, and chronic headaches.

The 4 included studies consistently demonstrated intracortical disinhibition in patients with MPS. Specifically, patients showed decreased short-interval intracortical inhibition (SICI) and/or increased intracortical facilitation (ICF) compared to healthy controls. These measurements were also correlated with psychological factors: in one study of 24 patients, intracortical facilitation was significantly associated with pain catastrophizing, while SICI correlated with pain pressure threshold scores. Another study of 47 patients found that anxiety was positively correlated with ICF and negatively correlated with cortical silent period.

A third study of 33 women found that non-responders to conditioned pain modulation showed increased ICF and higher brain-derived neurotrophic factor (BDNF) levels compared to responders. The fourth and largest study compared 54 MPS patients, 19 fibromyalgia patients, 27 osteoarthritis patients, and 14 healthy controls. MPS patients showed higher intracortical facilitation and lower SICI and cortical silent period compared to healthy controls. Notably, the cortical excitability patterns in MPS were very similar to those in fibromyalgia, but differed from osteoarthritis, where patients showed patterns closer to healthy controls.

However, when applying the Bradford Hill criteria, the researchers could not assert a strong causal relationship between these markers and MPS. While coherence, plausibility, and experimental evidence provided some support, the limited number of studies, modest effect sizes (R² = 0.19 for ICI and pressure pain threshold), lack of specificity (similar findings in fibromyalgia and neuropathic pain), and absence of temporal data weakened the causal argument.

This systematic review suggests that intracortical disinhibition, as measured by TMS, represents a consistent and reproducible neurophysiological finding in MPS that could potentially serve as an objective biomarker. For clinicians, this is significant because MPS currently lacks reliable objective diagnostic tests. The correlation between cortical disinhibition and psychological factors like anxiety and pain catastrophizing also highlights the interconnected nature of physical and psychological aspects of chronic pain. However, the review's conclusions must be tempered by important limitations.

All 4 studies came from a single research group, meaning independent replication is urgently needed. The studies included only women, limiting generalizability. Furthermore, because similar cortical disinhibition patterns appear in fibromyalgia, neuropathic pain, and other chronic pain conditions, these markers lack specificity for MPS alone—they may reflect a broader mechanism of central sensitization common to multiple chronic pain disorders rather than a unique signature of MPS. For patients, this research points toward future possibilities: if validated through larger, prospective studies, TMS measurements could eventually help diagnose MPS more objectively, predict treatment responses, and monitor whether interventions are working at the brain level.

The review also reinforces that treating MPS effectively may require addressing both peripheral muscle dysfunction and central nervous system changes, potentially through approaches like repetitive transcranial magnetic stimulation that can directly modulate cortical excitability.