Chemical Response Pattern of Different Classes of C-Nociceptors to Pruritogens and Algogens

1 Department of Physiology and Experimental Pathophysiology, University of Erlangen/Nuremberg, D-91054 Erlangen, Germany; 2 Department of Clinical Neurophysiology, University of Uppsala, S-75185 Uppsala, Sweden; 3 Department of Basic Oral Sciences, Karolinska Institute, S-14104 Huddinge, Sweden; 4 Department of Anesthesiology, Medical Faculty Mannheim, University of Heidelberg, 61087 Mannheim, Germany Schmelz, M., R. Schmidt, C. Weidner, Marita Hilliges, H. E. Torebjörk, and H. O. Handwerker. Chemical Response Pattern of Different Classes of C-Nociceptors to Pruritogens and Algogens. J. Neurophysiol. 89: 2441-2448, 2003. Vasoneuroactive substances were applied through intradermal microdialysis membranes and characterized as itch- or pain-inducing in psychophysical experiments. Histamine always provoked itching and rarely pain, capsaicin always pain but never itching. Prostaglandin E 2 (PGE 2 ) led preferentially to moderate itching. Serotonin, acetylcholine, and bradykinin induced pain more often than itching. Subsequently the same substances were used in microneurography experiments to characterize the sensitivity profile of human cutaneous C-nociceptors. The responses of 89 mechanoresponsive (CMH, polymodal nociceptors), 52 mechanoinsensitive, histamine-negative (CMi His ), and 24 mechanoinsensitive, histamine-positive (CMi His+ ) units were compared. CMi His+ units were most responsive to histamine and to PGE 2 and less to serotonin, ACh, bradykinin, and capsaicin. CMH units (polymodal nociceptors) and CMi His units showed significantly weaker responses to histamine, PGE 2 , and acetylcholine. Capsaicin and bradykinin responses were not significantly different in the two classes of mechano-insensitive units. We conclude that CMi His+ units are "selective," but not "specific" for pruritogenic substances and that the pruritic potency of a mediator increases with its ability to activate CMi His+ units but decreases with activation of CMH and CMi His units.