Altered experimental pain perception after cerebellar infarction

Abstract

Animal studies have suggested that the cerebellum, in addition to its motor functions, also has a role in pain processing and modulation, possibly because of its extensive connections with the prefrontal cortex and with brainstem regions involved in descending pain control. Consistently, human imaging studies have shown cerebellar activation in response to painful stimulation. However, it is presently not clear whether cerebellar lesions affect pain perception in humans. In the present study, we used experimental pain testing to compare acute pain perception and endogenous pain inhibition in 30 patients 1 to 11 years after cerebellar infarction and in 30 sex- and age-matched healthy control subjects. Compared to controls, patients exhibited a significantly increased pain perception in response to acute heat stimuli (44 °C-48 °C, average pain intensity rating for patients 3.4±2.8 and for controls 1.5±1.7 [on a numeric rating scale of 0-10], P<.01) and to repeated 256 mN pinprick stimuli (1.3±1.9 vs. 0.6±1.0 [0-10], P<.05). Heat hyperalgesia in patients was more pronounced on the body side ipsilateral to the infarction. In addition, patients showed reduced offset analgesia (change in pain intensity rating: 0.0%±15.8% vs. -16.9%±36.3%, P<.05) and reduced placebo analgesia (change in pain intensity rating: -1.0±1.1 vs. -1.8±1.3 [0-10], P<.05) compared to controls. In contrast, heat and pressure pain thresholds were not significantly different between groups. These results show that, after cerebellar infarction, patients perceive heat and repeated mechanical stimuli as more painful than do healthy control subjects and have deficient activation of endogenous pain inhibitory mechanisms (offset and placebo analgesia). This suggests that the cerebellum has a previously underestimated role in human pain perception and modulation.

Gray matter abnormalities associated with fibromyalgia: A meta-analysis of voxel-based morphometric studies

“…The present meta-analysis identified abnormalities in cerebellar lobule VIII, which is predominantly associated with sensorimotor function, and in lobules VIIb and Crus II, which are associated with higher-order (e.g., executive, emotional, and cognitive) processing [72][73][74][75][76][77][78], This suggests that the cerebellum has a previously underestimated role in patients with fibromyalgia, which might be of further interest and should be given more emphasis in future investigations.…”

“…This involves it in many cerebro-cerebellar circuits. Research implicates these circuits not only in sensorimotor processing but also in cognitive and affective functions, and more recently in pain perception and modulation [72][73][74][75][76][77][78]. Recent brain structural covariance network analysis of patients with fibromyalgia compared with healthy controls showed denser connections in the cerebellum and less-dense connections in the frontal lobe [39].…”

Altered Central Sensitization and Pain Modulation in the CNS in Chronic Joint Pain

“…However, few patient studies have been performed. Three studies have shown impaired offset analgesia in patients: one in diabetic polyneuropathy [77], one in cerebellar infarction [82], and one in painful neuropathic pain [69]. So far, no studies have been performed in patients with chronic joint pain.…”

Cerebellar Clustering and Functional Connectivity During Pain Processing

“…For allanalyses, theselected pthresholdwasselected using theFalse Discovery Rate with positive dependence assumption, FDRpN<0.05 andminimum clusters extent Ke> 500 mm 3 .Weused Chris Rorden's MRIcron software (http://www.nitrc.org/projects/mricron)to visualize and save images, overlayingtheGingerAle maps ontoaTalairachbrain template (created by [40]). …”

“…The cerebellum has been considered to be involved in pain processing: for instance, in rats, pain stimulation evokes changes in neural activity inthe posterior cerebellar vermis [2],andin humans, cerebellar lesion alteredpain perception [3].Asshowninalargefunctional magnetic resonance imaging-positron emission tomography (fMRI-PET) meta-analysis [4], the cerebellum is activated during painrelatedstimulation in conjunction with the areas typically associated with pain: the bilateral insula (with a right dominance),anterior cingulatecortex(ACC),bilateralprimary motor/sensory cortex (MI/SI), secondary somatosensory cortex (SII), posterior parietal cortex, andprefrontal cortex. Specifically, the nociceptive-related activation was observed in the deep cerebellar nuclei andanterior vermis IV-V, bilaterally in hemispheric lobules VI, VIIb, crus 1, and crus 2.…”