Midbrain control of spino-olivary neurones; a role in passive coping behaviour?

Stella Koutsikou, Lianne Leith, Richard Apps, Bridget Lumb. University of Bristol, Bristol, United Kingdom.

Studies of descending control of spinal nociception have focused primarily on sensory and autonomic functions and have neglected investigation of the control of pain pathways that convey inputs to motor control centres, such as the olivo-cerebellar system. This is a critical gap in our understanding of pain processing given that noxious stimuli drive powerful motor responses, which have important consequences for survival.

The aim of the current study was to examine the effects of neuronal activation in the ventrolateral PAG (vlPAG), which is a source of descending control and is implicated in coordinating passive coping behaviours, on responses of spino-olivary projection neurones in the dorsal horn to both innocuous and noxious peripheral stimulation.

In anaesthetised adult rats (n=16), extracellularly recorded antidromically activated spino-olivary neurones were characterised by their responses to peripheral stimulation and the effects of descending control following neuronal activation in the vlPAG were investigated. Application of low threshold (brush, tap, gentle pressure, joint movement) and high threshold (noxious pinch) mechanical stimuli to receptive fields on the hindlimb revealed four classes of neurones (Class 1-4). Responses of i) Class 2 and 3 neurones to noxious pinch (3.6N), ii) Class 1 and 2 neurones to innocuous pressure (0.6N) and iii) Class 4 neurones to joint movement were monitored before and after microinjection of an excitatory amino acid (50mM DL-homocysteic acid) into the vlPAG.

Activation in the vlPAG significantly depressed noxious pinch-evoked responses of Class 2 and 3 neurones. In contrast, activation in the vlPAG did not alter the responses of Class 2 spino-olivary neurones to innocuous pressure. Interestingly, activation in the vlPAG significantly enhanced responses of Class 4 spino-olivary neurones to joint movement.

The data reveal differential descending control exerted by the vlPAG on responses of spino-olivary neurones to sensory and proprioceptive stimuli, which we suggest could contribute to passive coping behaviours co-ordinated by the vlPAG.