Differentiation of Visceral and Cutaneous Pain in the Human Brain

Departments of 1 Physiology, and 2 Anesthesia, McGill University, Montreal, H3G 1Y6; 3 Département de Gastroenétrologie, Faculté de Médecine, 4 Départements de Stomatologie and 5 Centre de Recherché en Sciences Neurologiques, Faculté de Médecine Dentaire, Université de Montréal, Montreal, Quebec H3C 3J7 Canada Submitted 19 November 2002; accepted in final form 9 February 2003 The widespread convergence of information from visceral, cutaneous, and muscle tissues onto CNS neurons invites the question of how to identify pain as being from the viscera. Despite referral of visceral pain to cutaneous areas, individuals regularly distinguish cutaneous and visceral pain and commonly have contrasting behavioral reactions to each. Our study addresses this dilemma by directly comparing human neural processing of intensity-equated visceral and cutaneous pain. Seven subjects underwent fMRI scanning during visceral and cutaneous pain produced by balloon distention of the distal esophagus and contact heat on the midline chest. Stimulus intensities producing nonpainful and painful sensations, interleaved with rest periods, were presented in each functional run. Analyses compared painful to nonpainful conditions. A similar neural network, including secondary somatosensory and parietal cortices, thalamus, basal ganglia, and cerebellum, was activated by visceral and cutaneous painful stimuli. However, cutaneous pain evoked higher activation bilaterally in the anterior insular cortex. Further, cutaneous but not esophageal pain activated ventrolateral prefrontal cortex, despite higher affective scores for visceral pain. Visceral but not cutaneous pain activated bilateral inferior primary somatosensory cortex, bilateral primary motor cortex, and a more anterior locus within anterior cingulate cortex. Our results reveal a common cortical network subserving cutaneous and visceral pain that could underlie similarities in the pain experience. However, we also observed differential activation patterns within insular, primary somatosensory, motor, and prefrontal cortices that may account for the ability to distinguish visceral and cutaneous pain as well as the differential emotional, autonomic and motor responses associated with these different sensations. Address for reprint requests: M. C. Bushnell, Anesthesia Research Unit, Room 1220, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada (E-mail: catherine.bushnell{at}mcgill.ca ).