Human cerebellar responses to brush and heat stimuli in healthy and neuropathic pain subjects

Abstract

Though human pain imaging studies almost always demonstrate activation in the cerebellum, the role of the cerebellum in pain function is not well understood. Here we present results from two studies on the effects of noxious thermal heat and brush applied to the right side of the face in a group of healthy subjects (Group I) and a group of patients with neuropathic pain (Group II) who are more sensitive to both thermal and mechanical stimuli. Statistically significant activations and volumes of activations were defined in the cerebellum. Activated cerebellar structures were identified by colocalization of fMRI activation with the 'MRI Atlas of the Human Cerebellum'. Functional data (obtained using a 3T magnet) were defined in terms of maximum voxels and volume of activation in the cerebellum. Volume maps were then mapped onto two millimeter serial slices taken through the cerebellum in order to identify activation within regions defined by the activation volume. The data indicate that different regions of the cerebellum are involved in acute and chronic pain processing. Heat produces greater contralateral activation compared with brush, while brush resulted in more ipsilateral/bilateral cerebellar activation. Further, innocuous brush stimuli in healthy subjects produced decreased cerebellar activation in lobules concerned with somatosensory processing. The data also suggest a dichotomy of innocuous stimuli/sensorimotor cerebellum activation versus noxious experience/cognitive/limbic cerebellum activation. These results lead us to propose that the cerebellum may modulate the emotional and cognitive experience that distinguishes the perception of pain from the appreciation of innocuous sensory stimulation.

CNS activation maps in awake rats exposed to thermal stimuli to the dorsum of the hindpaw

“…Increased activation in lobules 3, 4 and Crus 2 was observed in this study. It is noteworthy that activation is observed in lobules 3, 4 (and 6) and Crus 2 in humans (Helmchen et al, 2003;Borsook et al, 2008).…”

Characterization of functional brain activity and connectivity using EEG and fMRI in patients with sickle cell disease

“…Recently, different regions of the cerebellum have been shown to be linked to several RSN. In particular, crus I have been shown to be linked to the salience network and ECN (Borsook et al, 2008, Caulfield et al, 2015). Our study showed that both the salience network and ECN have altered connectivity in SCD patients, and so this might also explain the negative connectivity in the patients.…”

In Vivo Quantification of Calcitonin Gene-Related Peptide Receptor Occupancy by Telcagepant in Rhesus Monkey and Human Brain Using the Positron Emission Tomography Tracer [11C]MK-4232

“…In vivo PET studies in rhesus monkeys show that [ 11 C]MK-4232 penetrates the blood-brain barrier (BBB) rapidly, with (Weiller et al, 1995;Bahra et al, 2001), and recent studies indicate that the cerebellum might have a role in nociception and migraine (Vincent and Hadjikhani, 2007;Borsook et al, 2008;Moulton et al, 2010). Spreading depression, cerebellar dysfunction, and familial hemiplegic migraine have also suggested a connection between the cerebellum and migraines.…”