Motor cortex pain compensation is modifiable: allostatic load degrades its analgesic efficiency and rehabilitation restores it
- 1Spaulding Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical School
Abstract
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.
Related
- Target Precision Shapes Trunk Compensation After Stroke: Neuromechanical Consequences for Upper Limb Rehabilitation
- Smartphone-based real-time feedback to suppress trunk compensation for unsupervised upper limb rehabilitation in patients with brain disorders
- Indicators of spectral analysis as biomarkers for monitoring the efficiency of readaptation in military servicemen with previous experience in mixed martial arts during the period of long-term rehabilitation after wounds
- Persistent Alzheimer-related molecular dysregulation after cerebral ischemia: a hierarchical-circular hypothesis of impaired allostatic recovery
- The prison-to-community transition as a neuropeptide stress test: an allostatic continuity agenda for addiction care.
BibTeX
@misc{fregni2026motor,
title = {{Motor cortex pain compensation is modifiable: allostatic load degrades its analgesic efficiency and rehabilitation restores it}},
author = {F. Fregni and M. Imamura and L. Camargo and K. Pacheco-Barrios and A. C. Lepesteur Gianlorenco and L. Battistella and W. Caumo},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.21.26363555},
url = {https://www.medrxiv.org/content/10.64898/2026.09.21.26363555v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Motor cortex pain compensation is modifiable: allostatic load degrades its analgesic efficiency and rehabilitation restores it
AU - F. Fregni
AU - M. Imamura
AU - L. Camargo
AU - K. Pacheco-Barrios
AU - A. C. Lepesteur Gianlorenco
AU - L. Battistella
AU - W. Caumo
PY - 2026
DA - 2026/09/21
PB - medRxiv
DO - 10.64898/2026.09.21.26363555
UR - https://www.medrxiv.org/content/10.64898/2026.09.21.26363555v1
AB - 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.
ER -