Cortical responses to salient nociceptive and not nociceptive stimuli in vegetative and minimal conscious state.

Marina De Tommaso,Jorge Navarro,Katia Ricci,Francesca Buonocunto,Giulio E Lancioni,Crocifissa Lanzillotti,Paolo Livrea

doi:10.3389/fnhum.2015.00017

Abstract

Aims: Questions regarding perception of pain in non-communicating patients and the management of pain continue to raise controversy both at a clinical and ethical level. The aim of this study was to examine the cortical response to salient visual, acoustic, somatosensory electric non-nociceptive and nociceptive laser stimuli and their correlation with the clinical evaluation.Methods: Five Vegetative State (VS), 4 Minimally Conscious State (MCS) patients and 11 age- and sex-matched controls were examined. Evoked responses were obtained by 64 scalp electrodes, while delivering auditory, visual, non-noxious electrical and noxious laser stimulation, which were randomly presented every 10 s. Laser, somatosensory, auditory and visual evoked responses were identified as a negative-positive (N2-P2) vertex complex in the 500 ms post-stimulus time. We used Nociception Coma Scale-Revised (NCS-R) and Coma Recovery Scale (CRS-R) for clinical evaluation of pain perception and consciousness impairment.Results: The laser evoked potentials (LEPs) were recognizable in all cases. Only one MCS patient showed a reliable cortical response to all the employed stimulus modalities. One VS patient did not present cortical responses to any other stimulus modality. In the remaining participants, auditory, visual and electrical related potentials were inconstantly present. Significant N2 and P2 latency prolongation occurred in both VS and MCS patients. The presence of a reliable cortical response to auditory, visual and electric stimuli was able to correctly classify VS and MCS patients with 90% accuracy. Laser P2 and N2 amplitudes were not correlated with the CRS-R and NCS-R scores, while auditory and electric related potentials amplitude were associated with the motor response to pain and consciousness recovery.Discussion: pain arousal may be a primary function also in vegetative state patients while the relevance of other stimulus modalities may indicate the degree of cognitive and motor behavior recovery. This underlines the importance of considering the potential experience of pain also in patients in vegetative state and to appropriately assess a possible treatment also in those patients.

Highlights

Pain and pleasure are inherently subjective experiences that persons can communicate to others verbally and non-verbally (Merskey et al, 1994)
Laser P2 and N2 amplitudes were not correlated with the Coma Recovery Scale-Revised (CRS-R) and Nociception Coma Scale-Revised (NCS-R) scores, while auditory and electric related potentials amplitude were associated with the motor response to pain and consciousness recovery
The negative-positive complex obtained from auditory, visual and somatosensory nonnociceptive stimuli resembled the morphology and topographic distribution of the laser N2-P2 waves, confirming that pain may activate the same cortical zones as other potentially relevant stimuli

Summary

Introduction

Pain and pleasure are inherently subjective experiences that persons can communicate to others verbally and non-verbally (Merskey et al, 1994). In non-communicative, severely brain damaged patients, we can only infer those experiences by evaluating behavioral responses to external stimuli. Questions regarding perception and management of pain in non-communicating patients continue to raise controversy both at a clinical and ethical level (Demertzi et al, 2013). Neuroimaging studies have shown that disorders of consciousness are characterized by distinct cerebral patterns in response to sensory stimulation (Laureys et al, 2002; Kassubek et al, 2003; Boly et al, 2008; Zanatta et al, 2012). In 15 VS patients, they found no evidence of noxious stimulation-related downstream activation beyond primary somatosensory cortex. Functional connectivity assessment showed that the observed cortical activation subsisted as an island, dissociated from the pain matrix and the higher-order cortices that

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Conclusion