Disorders of Consciousness: Painless or Painful Conditions?—Evidence from Neuroimaging Studies

Abstract

The experience of pain in disorders of consciousness is still debated. Neuroimaging studies, using functional Magnetic Resonance Imaging (fMRI), Positron Emission Tomography (PET), multichannel electroencephalography (EEG) and laser-evoked potentials, suggest that the perception of pain increases with the level of consciousness. Brain activation in response to noxious stimuli has been observed in patients with unresponsive wakefulness syndrome (UWS), which is also referred to as a vegetative state (VS), as well as those in a minimally conscious state (MCS). However, all of these techniques suggest that pain-related brain activation patterns of patients in MCS more closely resemble those of healthy subjects. This is further supported by fMRI findings showing a much greater functional connectivity within the structures of the so-called pain matrix in MCS as compared to UWS/VS patients. Nonetheless, when interpreting the results, a distinction is necessary between autonomic responses to potentially harmful stimuli and conscious experience of the unpleasantness of pain. Even more so if we consider that the degree of residual functioning and cortical connectivity necessary for the somatosensory, affective and cognitive-evaluative components of pain processing are not yet clear. Although procedurally challenging, the particular value of the aforementioned techniques in the assessment of pain in disorders of consciousness has been clearly demonstrated. The study of pain-related brain activation and functioning can contribute to a better understanding of the networks underlying pain perception while addressing clinical and ethical questions concerning patient care. Further development of technology and methods should aim to increase the availability of neuroimaging, objective assessment of functional connectivity and analysis at the level of individual cases as well as group comparisons. This will enable neuroimaging to truly become a clinical tool to reliably investigate pain in severely brain-injured patients as well as an asset for research.

Measures of CNS-Autonomic Interaction and Responsiveness in Disorder of Consciousness

“…A 2006 provocative report presented the case of a VS/UWS subject able to engage in mental tasks as indicated by her fMRI patterns of brain activations (Owen et al, 2006). Levels of responsiveness involving higher brain functions have been observed in subjects otherwise classified as VS/UWS according to clinical criteria (Laureys et al, 2007; Boly et al, 2008; Bruno et al, 2010; Owen, 2014; Pistoia et al, 2016; Riganello et al, 2018b). These observations were mostly based on regional brain activation in response to stimulus conditions in controlled setups; stimulus-related functional changes in the autonomic nervous system (ANS) function have also been described.…”

Pain in Decreased Consciousness Patients

“…Spinomesencephalic tract begins in the spinal cord, passes through the medulla oblongata and pons, and ends in the periaqueductal gray. 12 Second-order neurons ending in the thalamus will synapse with third-order neurons projected to the primary sensory cortex. In addition, order III neurons will also project to the secondary sensory cortex and insula in terms of the perception of the sublime function of pain.…”

Time-Delay Latency of Resting-State Blood Oxygen Level-Dependent Signal Related to the Level of Consciousness in Patients with Severe Consciousness Impairment

“…Related to these sensorimotor functions of the cingulate cortex, the activity generated by nociceptive stimuli is located mainly in mCC and is altered in DOC patients (Laureys et al, 2002). In particular, the linkage between pain processing and movement is severely affected in patients with UWS (Pistoia et al, 2016).…”