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

The primary motor cortex is a critical hub for pain control, yet its few identified regulatory mechanisms - intracortical inhibition and oscillatory markers - predict symptoms inconsistently. The prevailing view holds that pain results from reduced inhibition, a fixed deficit, rather than from resistance to inhibition that rehabilitation can reverse. Here we show that motor cortex pain compensation is instead a modifiable state whose analgesic efficiency depends on allostatic load. In a fibromyalgia trial and a knee osteoarthritis cohort assessed with parallel EEG and transcranial magnetic stimulation, a signature combining central theta asymmetry and intracortical inhibition was unrelated or inversely related to symptom burden under low allostatic load but positively related to it under high load in fibromyalgia, and its protective association was attenuated under high load in osteoarthritis - the same signal carrying different clinical meaning. A burden-adjusted index modelled on the homeostatic model assessment of insulin resistance was elevated under high load, predicted improvement after rehabilitation beyond baseline severity, and fell in responders but not in non-responders; in both cohorts the neurophysiological component itself recalibrated with response. Motor cortex compensation is thus degraded by allostatic load and restored by rehabilitation.