Investigating brain dysfunction in neuropathic pain with MRI.

Abstract

Neuropathic pain is a severe chronic disease following nervous system lesions. Allodynia is a main symptom of neuropathic pain, and it can be easily triggered by normally innocuous stimuli inside a functional MRI magnet. In this new series of 35 patients (age ranges: 33-82 years old, 14 females, 21 males, peripheral neuropathic pain: 4, central neuropathic pain: 31), we investigated mechanical dynamic and thermal cold allodynia. Patients were enrolled for the study if allodynia was intense on one part of the body and very slight-or absent-on another part of the body. Allodynia was associated mainly with bilateral increases of activity in anterior insular cortices, anterior mid-cingulate cortex, prefrontal cortex and secondary somatosensory cortices. Most of these activities were correlated with the subjective perception of allodynia, and thus, they dealt with abnormal pain perception. Since these patients also had sensory loss in or around the areas of allodynia, we examined the hypothesis of structural abnormalities in brain structures receiving sensory inputs. Secondary somatosensory cortex ipsilateral to pain showed grey matter loss, and there was a correlation between sensory loss and grey matter density in the lateral thalamus contralateral to pain. The allodynic brain activations were found to be influenced by individual variables describing the patients: the inclination of the patients to experience provoked pain-as defined by quantitative sensory testing/laser-evoked potentials-exacerbated secondary somatosensory cortices activations during allodynia, with the possible consequence that excito-toxicity or similar mechanisms could (secondarily) lead to structural abnormalities. Conversely, we found a negative weighting of ongoing pain level on the allodynic responses in contralateral anterior insula, frontal operculum and parts of secondary somatosensory cortices, suggesting that these regions previously engaged in spontaneous pain had limited possibilities to further increase their response in case of allodynia. In this new series of patients, we confirmed that brain areas that are normally not involved during innocuous stimulations became overactive in case of mechanical allodynia. These results suggest that the above-reported areas could be new targets for neuromodulation techniques with the aim to induce pain relief.