Basal ganglia modulation of trigeminal intralaminar nuclei thalamic activity

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DESCRIPTION (provided by applicant): The motor symptoms and underlying neuropathology resulting from damage to the basal ganglia such as that in Parkinson's disease (PD) have been described extensively. However, the basal ganglia role in somatosensory function, including that of pain and nociception, has been largely ignored. The proposed use of electrophysic-logical methods explores how the basal ganglia modulate the response of nociceptive neurons in the intralaminar nuclei of the thalamus to persistent trigeminal nociceptive stimuli. Our long range goal is to understand how the basal ganglia modulate nociceptive information. Dopaminergic degeneration of the nigrostriatal pathway is expected to enhance the response of thalamic neurons to persistent nociceptive trigeminal stimuli. The first specific aim is to analyze the connectivity between the caudate- putamen (CPu) and intralaminar nuclei of the thalamus by testing the effects of electrical CPu stimulation on the responsiveness of nociceptive neurons in the intralaminar nuclei of the thalamus. Activation of the CPu by electrical stimulation is expected to alter the discharge frequency of nociceptive thalamic neurons to noxious chemical and mechanical stimulation of the face. These electrophysiological experiments will also permit functional characterization,of a nociceptive thalamostriatal pathway. This thalamostriatal pathway has not been described previously. The second specific aim is to test the effects of dopamine depletion on the responsiveness of trigeminal nociceptive neurons in the intralaminar nuclei of the thalamus and investigate how dopamine depletions affects pain behavior. Unilateral injection of 6-hydroxydopamine into the CPu to destroy dopamine-containing neurons is expected to alter the evoked discharge frequency of nociceptive neurons in the intralaminar nuclei of the thalamus and increase nociceptive behavioral responses. These experiments will provide new insights about the role of the basal ganglia in pain and nociception and will shed light on a new dopaminergic pain modulatory system. It is possible that pain observed patients with PD is caused by an impairment of this pain modulatory system. These studies will help explain the complex sensory symptoms exhibited by patients with PD and may suggest new treatment strategies to alleviate such pain.