Beyond motor control: the subthalamic nucleus as a central hub for pain in Parkinson’s disease

Benazzouz A(1), Molpeceres-Sierra E(2), Bouali-Benazzouz R(3), Fossat P(4).

Author information:
(1)Université de Bordeaux Collège Sciences de la Santé, Bordeaux,
Nouvelle-Aquitaine FRANCE. Electronic address:
.
(2)Université de Bordeaux Collège Sciences de la Santé. Electronic address:
.
(3)Université de Bordeaux Collège Sciences de la Santé. Electronic address:
.
(4)Université de Bordeaux Collège Sciences de la Santé. Electronic address:
.

The subthalamic nucleus (STN), considered a primarily motor structure within the
basal ganglia, is recognized as a key contributor to a wider set of behaviors.
Among these, nociceptive processing has gained particular attention, especially
given the high prevalence and early emergence of pain in Parkinson’s disease
(PD). This review brings together anatomical, physiological and translational
evidence to examine how the STN integrates motor and nociceptive information.
The STN receives ascending afferents from brainstem nociceptive pathways and its
activity tracks the intensity and salience of noxious stimuli, recruiting
cortical and limbic networks that shape both sensory and affective dimensions of
pain. In PD, the organization and dynamics of the STN are profoundly disrupted.
Abnormal bursting and exaggerated beta oscillations, central to motor symptoms,
also appear to promote central sensitization and enhanced pain responses.
Studies from animal models consistently support the notion that parkinsonian
states perturbate nociceptive signaling within the STN. Deep brain stimulation
(DBS) of the STN, a well-established therapy for motor symptoms, further
demonstrates the involvement of the nucleus in the pathophysiology of pain.
Evidence from clinical and preclinical studies indicates that STN-DBS attenuates
nociceptive hypersensitivity and modulates pain processing at spinal level,
suggesting an intrinsic analgesic action rather than a secondary effect of motor
improvement. Finally, recent optogenetic and chemogenetic approaches clarified
how therapeutic interventions act on STN circuits, showing that symptom relief
is linked to the suppression of pathological firing patterns. Together, these
findings position the STN as a central node linking motor and pain networks in
PD.

Copyright © 2026. Published by Elsevier Ltd.

DOI: 10.1016/j.neubiorev.2026.106691
PMID: 42002247

Auteurs Bordeaux Neurocampus