Imaging the neural correlates of neuropathic pain and pleasurable relief associated with inherited erythromelalgia in a single subject with quantitative arterial spin labelling

• Published in: Pain (Amsterdam) Vol. 153; no. 5; pp. 1122 - 1127
• Main Authors: Segerdahl, Andrew R., Xie, Jingyi, Paterson, Kathryn, Ramirez, Juan D., Tracey, Irene, Bennett, David L.H.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Elsevier B.V 01.05.2012; Lippincott Williams & Wilkins, Inc; Elsevier; Lippincott Williams & Wilkins
• Subjects: Adult; Arterial spin labelling; Biological and medical sciences; Brain - physiopathology; Clinical Note; Erythromelalgia; Erythromelalgia - genetics; Erythromelalgia - physiopathology; Female; FMRI; Functional Neuroimaging - methods; Fundamental and applied biological sciences. Psychology; Humans; Illness and personality; Illness, stress and coping; NAV1.7 Voltage-Gated Sodium Channel; Neuralgia - genetics; Neuralgia - physiopathology; Neuropathic pain; Pleasure - physiology; Psychology and medicine; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Sensory Thresholds - physiology; Sodium Channels - genetics; Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors; Spin Labels; Vertebrates: nervous system and sense organs; Erythromelalgia; Arterial spin labelling; FMRI; Neuropathic pain; Human; Temperature; Cooling; Hypersensitivity; Nuclear magnetic resonance imaging; Foot; Pain; Neuron; Sodium; Voltage; Mutation; Technique
• ISSN: 0304-3959; 1872-6623; 1872-6623
• DOI: 10.1016/j.pain.2011.12.012

Using a composite diagnostic-neuroimaging approach, this study shows the modulatory effects of pleasant cooling on pain-related cortical regions in a subject suffering from inherited erythromelalgia. We identified a patient with severe inherited erythromelalgia secondary to an L858F mutation in the voltage-gated sodium channel Nav1.7. The patient reported severe ongoing foot pain, which was exquisitely sensitive to limb cooling. We confirmed this heat hypersensitivity using quantitative sensory testing. Additionally, we employed a novel perfusion imaging technique in a simple block design to assess her baseline erythromelalgia pain vs cooling relief. Robust activations of key pain, pain-affect, and reward-related centres were observed. This combined approach allowed us to confirm the presence of a temperature-sensitive channelopathy of peripheral neurons and to investigate the neural correlates of tonic neuropathic pain and relief in a single subject.