Motor cortex stimulation is generally suggested as a therapy for patients with chronic and refractory neuropathic pain. However, the mechanisms underlying its analgesic effects are still unknown. In a previous study, we demonstrated that cortical stimulation increases the nociceptive threshold of naive conscious rats with opioid participation. In the present study, we investigated the neurocircuitry involved during the antinociception induced by transdural stimulation of motor cortex in naive rats considering that little is known about the relation between motor cortex and analgesia. The neuronal activation patterns were evaluated in the thalamic nuclei and midbrain periaqueductal gray. Neuronal inactivation in response to motor cortex stimulation was detected in thalamic sites both in terms of immunolabeling (Zif268/Fos) and in the neuronal firing rates in ventral posterolateral nuclei and centromedian-parafascicular thalamic complex. This effect was particularly visible for neurons responsive to nociceptive peripheral stimulation. Furthermore, motor cortex stimulation enhanced neuronal firing rate and Fos immunoreactivity in the ipsilateral periaqueductal gray. We have also observed a decreased Zif268, δ-aminobutyric acid (GABA), and glutamic acid decarboxylase expression within the same region, suggesting an inhibition of GABAergic interneurons of the midbrain periaqueductal gray, consequently activating neurons responsible for the descending pain inhibitory control system. Taken together, the present findings suggest that inhibition of thalamic sensory neurons and disinhibition of the neurons in periaqueductal gray are at least in part responsible for the motor cortex stimulation-induced antinociception.

Objective: To prospectively evaluate the effect of subthalamic nucleus deep brain stimulation (STN-DBS) on the different characteristics of pain and other nonmotor symptoms (NMS) in patients with Parkinson disease (PD). Methods: Forty-four patients with PD and refractory motor symptoms were screened for STN-DBS. Patients were evaluated before and 1 year after surgery. The primary outcome was change in pain prevalence after surgery. Secondary outcome measures were changes in motor function (Unified Parkinson9s Disease Rating Scale), characteristics of pain and other NMS using specific scales and questionnaires, and quality of life. Results: Forty-one patients completed the study. The prevalence of pain changed from 70% to 21% after surgery (p < 0.001). There were also significant improvements in pain intensity, NMS, and quality of life after STN-DBS (p < 0.05). Dystonic and musculoskeletal pain responded well to DBS, while central pain and neuropathic pain were not influenced by surgery. There was a strong correlation between the change in pain intensity and the improvement in quality of life (r = 0.708, p < 0.005). No correlation was found between pain improvement and preoperative response to levodopa or motor improvement during stimulation (r = 0.247, p = 0.197 and r = 0.249, p = 0.193, respectively) or with changes in other NMS. Conclusions: STN-DBS decreased pain after surgery, but had different effects in different types of PD-related pain. Motor and nonmotor symptom improvements after STN-DBS did not correlate with pain relief. Classification of evidence: This study provides Class IV evidence that in patients with idiopathic PD with refractory motor fluctuations, STN-DBS decreases the prevalence of pain and improves quality of life.

Pain and sensory abnormalities are present in a large proportion of Parkinson disease (PD) patients and have a significant negative impact in quality of life. It remains undetermined whether pain occurs secondary to motor impairment and to which extent it can be relieved by improvement of motor symptoms. The aim of this review was to examine the current knowledge on the mechanisms behind sensory changes and pain inPDand to assess the modulatory effects of motor treatment on these sensory abnormalities. A comprehensive literature search was performed. We selected studies investigating sensory changes and pain inPDand the effects of levodopa administration and deep brain stimulation (DBS) on these symptoms.PDpatients have altered sensory and pain thresholds in the off‐medication state. Both levodopa andDBSimprove motor symptoms (i.e.: bradykinesia, tremor) and change sensory abnormalities towards normal levels. However, there is no direct correlation between sensory/pain changes and motor improvement, suggesting that motor and non‐motor symptoms do not necessarily share the same mechanisms. Whether dopamine andDBShave a real antinociceptive effect or simply a modulatory effect in pain perception remain uncertain. These data may provide useful insights into a mechanism‐based approach to pain inPD, pointing out the role of the dopaminergic system in pain perception and the importance of the characterization of different pain syndromes related toPDbefore specific treatment can be instituted.

Cerebral hemodynamics and metabolism are frequently impaired in a wide range of neurological diseases, including traumatic brain injury and stroke, with several pathophysiological mechanisms of injury. The resultant uncoupling of cerebral blood flow and metabolism can trigger secondary brain lesions, particularly in early phases, consequently worsening the patient's outcome. Cerebral blood flow regulation is influenced by blood gas content, blood viscosity, body temperature, cardiac output, altitude, cerebrovascular autoregulation, and neurovascular coupling, mediated by chemical agents such as nitric oxide (NO), carbon monoxide (CO), eicosanoid products, oxygen-derived free radicals, endothelins, K+, H+, and adenosine. A better understanding of these factors is valuable for the management of neurocritical care patients. The assessment of both cerebral hemodynamics and metabolism in the acute phase of neurocritical care conditions may contribute to a more effective planning of therapeutic strategies for reducing secondary brain lesions. In this review, the authors have discussed concepts of cerebral hemodynamics, considering aspects of clinical importance.