Pain is a frequent and poorly treated symptom of
Parkinson's disease, mainly due to scarce knowledge of its basic mechanisms. In
Parkinson's disease,
deep brain stimulation of the subthalamic nucleus is a successful treatment of motor symptoms, but also might be effective in treating
pain. However, it has been unclear which type of
pain may benefit and how neurostimulation of the subthalamic nucleus might interfere with
pain processing in
Parkinson's disease. We hypothesized that the subthalamic nucleus may be an effective access point for modulation of neural systems subserving pain perception and processing in
Parkinson's disease. To explore this, we discuss data from human neurophysiological and psychophysical investigations. We review studies demonstrating the clinical efficacy of
deep brain stimulation of the subthalamic nucleus for
pain relief in
Parkinson's disease. Finally, we present some of the key insights from investigations in animal models, healthy humans and
Parkinson's disease patients into the aberrant neurobiology of
pain processing and consider their implications for the
pain-relieving effects of subthalamic nucleus neuromodulation. The evidence from clinical and experimental studies supports the hypothesis that altered central processing is critical for
pain generation in
Parkinson's disease and that the subthalamic nucleus is a key structure in pain perception and modulation. Future preclinical and clinical research should consider the subthalamic nucleus as an entry point to modulate different types of
pain, not only in
Parkinson's disease but also in other neurological conditions associated with abnormal
pain processing.