Activation of superficial dorsal horn neurons in the mouse by a PAR-2 agonist and 5-HT: potential role in itch.
Itch, an unpleasant sensation associated with the desire to scratch, is symptomatic of dermatologic and systemic disorders that often resist antihistamine treatment. Histamine-independent itch mediators include serotonin (5-HT) and agonists of the protease-activated receptor-2 (PAR-2). We used behavior, Fos immunohistochemistry, and electrophysiology to investigate if these mediators activate spinal dorsal horn neurons in a manner consistent with itch. Intradermal (i.d.) injection of the PAR-2 agonist SLIGRL-NH(2) in the rostral back evoked bouts of directed hindlimb scratches over 20-30 min. Hindpaw injection of SLIGRL-NH(2) produced Fos staining in superficial dorsal horn which was then targeted for single-unit recording. Small id microinjections of SLIGRL-NH(2) or 5-HT identified responsive single units in the superficial dorsal horn of mice anesthetized with pentobarbital. Thirty-eight units characterized as wide dynamic range, nociceptive specific, or mechanically insensitive exhibited significantly increased firing after i.d. SLIGRL-NH(2) for 9 min, to partial (25%) tachyphylaxis with repeated injection. A majority additionally responded to 5-HT (70%), mustard oil (79%), and capsaicin (71%). Seven units isolated with the 5-HT search stimulus exhibited significant and prolonged responses to 5-HT with tachyphylaxis to repeated injections. The majority also responded to SLIGRL-NH(2), mustard oil, and capsaicin. The prolonged responses of superficial dorsal horn neurons to SLIGRL-NH(2) and 5-HT suggest a role in signaling itch. However, their responsiveness to algogens is inconsistent with itch specificity. Alternatively, such neurons may signal itch, whereas noxious stimulus levels recruit these and a larger population of pruritogen-insensitive cells to signal pain which masks or occludes the itch signal.
Akiyama
Tasuku
T
Department of Neurobiology, Physiology, and Behavior, University of California, Davis, Davis, California 95616, USA.
Merrill
Austin W
AW
Carstens
Mirela Iodi
MI
Carstens
E
E
D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009842:Oligopeptides / Q000494:pharmacology; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D020671:Posterior Horn Cells / Q000187:drug effects*; D011537:Pruritus / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D044464:Receptor, PAR-2 / Q000819:agonists*; D018160:Receptors, Cytoplasmic and Nuclear; D012701:Serotonin / Q000494:pharmacology*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D009842:Oligopeptides; D016761:Oncogene Proteins v-fos; D044464:Receptor, PAR-2; D018160:Receptors, Cytoplasmic and Nuclear; C112356:seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide; D012701:Serotonin