Evidence of a Specific Spinal Pathway for the Sense of Warmth in Humans

1 Dipartimento Scienze Neurologiche, Università "La Sapienza," 00185 Rome; 2 Micromed, 31021 Treviso; and 3 NeuroMed Institute, 86077 Pozzilli, Italy Iannetti, G.D., A. Truini, A. Romaniello, F. Galeotti, C. Rizzo, M. Manfredi, and G. Cruccu. Evidence of a Specific Spinal Pathway for the Sense of Warmth in Humans. J. Neurophysiol. 89: 562-570, 2003. While research on human sensory processing shows that warm input is conveyed from the periphery by specific, unmyelinated primary sensory neurons, its pathways in the central nervous system (CNS) remain unclear. To gain physiological information on the spinal pathways that convey warmth or nociceptive sensations, in 15 healthy subjects, we studied the cerebral evoked responses and reaction times in response to laser stimuli selectively exciting A nociceptors or C warmth receptors at different levels along the spine. To minimize the conduction distance along the primary sensory neuron, we directed CO 2 -laser pulses to the skin overlying the vertebral spinous processes. Using brain source analysis of the evoked responses with high-resolution electroencephalography and a realistic model of the head based on individual magnetic resonance imaging scans, we also studied the cortical areas involved in the cerebral processing of warm and nociceptive inputs. The activation of C warmth receptors evoked cerebral potentials with a main positive component peaking at 470-540 ms, i.e., a latency clearly longer than that of the corresponding wave yielded by A nociceptive input (290-320 ms). Spinal neurons activated by the warm input had a slower conduction velocity (2.5 m/s) than the nociceptive spinal neurons (11.9 m/s). Brain source analysis of the cerebral responses evoked by the A input yielded a very strong fit for one single generator in the mid portion of the cingulate gyrus; the warmth-related responses were best explained by three generators, one within the cingulate and two in the right and left opercular-insular cortices. Our results support the existence of slow-conducting second-order neurons specific for the sense of warmth.