The cerebellum is critically involved in motor control; however there is evidence to indicate that it also has a role in nociceptive processing. Previous studies suggest a dual role, whereby stimulation of the anterior lobe of the cerebellum invokes antinociception (1-3), and posterior lobe stimulation invokes pronociception (4,5). However, these data are difficult to interpret with respect to (i) somatic nociceptive pathways as they investigated visceral nociception and (ii) precise localisation of the origin of descending control as previous studies utilised electrical stimulation of the cerebellum, where current spread to neighbouring structures, activation of fibres of passage and antidromic activation are important confounds. The aim therefore of the present study was to investigate modulation of somatic nociception in rats following activation of the anterior (lobule V) and posterior (lobule VIII) lobes of the cerebellum using DL Homocysteic acid (DLH), an excitatory amino acid that allows cerebellar activation to be restricted to target neurons thereby overcoming some of the limitations of electrical stimulation. Rats were initially anaesthetised with halothane (2-3% in 02) delivered by face mask and maintained with a continuous infusion of alfaxalone (25mg/kg/hour i.v). EMG was recorded from the biceps femoris while pinching the ipsilateral hindpaw. The change in mechanical withdrawal threshold (the force required to elicit an EMG response) and magnitude of EMG activity at threshold was assessed following injection of either DLH (0.1M) or an equivalent volume of saline into lobule VIII (n=8 and n=7 respectively), or lobule V (n=4 and n=5 respectively) of the cerebellar cortex. Values are mean ± SEM compared by paired t test. Pronociception was observed following lobule VIII stimulation, indicated by a statistically significant decrease on average of 23% in mechanical withdrawal threshold following DLH injection (from 56.5 ± 5.0 g/mm2 to 43.2 ± 4.3 g/mm2 , P=0.0038). There was also a statistically significant facilitation on average of 63% in EMG activity (from 0.007 ± 0.002 v/s to 0.012 ± 0.002 v/s, P= 0.0077). In contrast, there was no statistically significant change in mechanical withdrawal threshold or EMG activity following DLH administration into lobule V or after injection of saline in either lobule VIII or V. These data indicate that stimulation of the anterior and posterior lobe of the cerebellum has a differential effect on nociceptive processing, which may be explained by activation of different cerebellar modules. However, recording EMG responses does not discriminate between effects due to modulation of sensory and/or motor components of the spinal pathways activated by the noxious stimulus. Further experiments will therefore investigate cerebellar modulation of sensory input by making recordings from dorsal horn neurons.
37th Congress of IUPS (Birmingham, UK) (2013) Proc 37th IUPS, PCD167
Poster Communications: Role of the cerebellum in descending control of nociception
N. Weerasinghe1, B. M. Lumb1, R. Apps1, J. C. Murrell1
1. Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom.
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Where applicable, experiments conform with Society ethical requirements.