Motor cortex pain compensation is modifiable: allostatic load degrades its analgesic efficiency and rehabilitation restores it

Pain control depends critically on the primary motor cortex, but only a few regulatory mechanisms have been identified—intracortical inhibition and oscillatory markers—and they predict symptoms inconsistently. The prevailing view treats pain as a fixed deficit of reduced inhibition, rather than resistance to inhibition that rehabilitation might reverse.

Using a fibromyalgia trial and a knee osteoarthritis cohort assessed with parallel EEG and transcranial magnetic stimulation, the authors examined a signature combining central theta asymmetry and intracortical inhibition. Under low allostatic load, this signature was unrelated or inversely related to symptom burden, whereas under high allostatic load it was positively related to symptom burden in fibromyalgia. In osteoarthritis, its protective association was attenuated under high load, indicating that the same neurophysiological signal can have different clinical meaning depending on allostatic load.

The authors then tested a burden-adjusted index modeled on the homeostatic model assessment of insulin resistance (HOMA-IR). This index was elevated under high allostatic load and predicted improvement after rehabilitation beyond baseline severity. It fell in responders but not in non-responders, and in both cohorts the neurophysiological component itself recalibrated with response.

Together, the results indicate that motor cortex pain compensation is degraded by allostatic load and restored by rehabilitation, supporting a modifiable rather than fixed-deficit model of pain-related motor cortex dysfunction.