title: Catecholamine-induced excitation of nociceptors in sympathetically maintained pain.
abstract: Sympathetically maintained pain could either be mediated by ephaptic interactions between sympathetic efferent and afferent nociceptive fibers or by catecholamine-induced activation of nociceptive nerve endings. We report here single fiber recordings from C nociceptors in a patient with sympathetically maintained pain, in whom sympathetic blockade had repeatedly eliminated the ongoing pain in both legs. We classified eight C-fibers as mechano-responsive and six as mechano-insensitive nociceptors according to their mechanical responsiveness and activity-dependent slowing of conduction velocity (latency increase of 0.5+/-1.1 vs. 7.1+/-2.0 ms for 20 pulses at 0.125 Hz). Two C-fibers were activated with a delay of several seconds following strong endogenous sympathetic bursts; they were also excited for about 3 min following the injection of norepinephrine (10 microl, 0.05%) into their innervation territory. In these two fibers, a prolonged activation by injection of low pH solution (phosphate buffer, pH 6.0, 10 microl) and sensitization of their heat response following prostaglandin E2 injection were recorded, evidencing their afferent nature. Moreover, their activity-dependent slowing was typical for mechano-insensitive nociceptors. We conclude that sensitized mechano-insensitive nociceptors can be activated by endogenously released catecholamines and thereby may contribute to sympathetically maintained pain. No evidence for ephaptic interaction between sympathetic efferent and nociceptive afferent fibers was found.
authors.affiliation: Laboratory of Clinical Neurophysiology, Department of Neurology, Rikshospitalet University Hospital, Oslo, Norway Department of Physiology and Experimental Pathophysiology, University of Erlangen/Nürnberg, Germany Department of Clinical Neurophysiology, University Hospital, Uppsala, Sweden Department of Basic Oral Sciences, Karolinska Institute, Huddinge, Sweden Department of Anesthesiology, Rikshospitalet University Hospital, Oslo, Norway Department of Anesthesiology and Operative Intensive Care, Mannheim, University Heidelberg, Germany.
authors.forename: Ellen
authors.initials: E
authors.lastname: Jørum
authors.forename: Kristin
authors.initials: K
authors.lastname: Ørstavik
authors.forename: Roland
authors.initials: R
authors.lastname: Schmidt
authors.forename: Barbara
authors.initials: B
authors.lastname: Namer
authors.forename: Richard W
authors.initials: RW
authors.lastname: Carr
authors.forename: Gunnvald
authors.initials: G
authors.lastname: Kvarstein
authors.forename: Marita
authors.initials: M
authors.lastname: Hilliges
authors.forename: Hermann
authors.initials: H
authors.lastname: Handwerker
authors.forename: Erik
authors.initials: E
authors.lastname: Torebjörk
authors.forename: Martin
authors.initials: M
authors.lastname: Schmelz
mesh_terms: D000328:Adult; D002395:Catecholamines / Q000378:metabolism*; D006801:Humans; D006930:Hyperalgesia / Q000503:physiopathology*; D007866:Leg / Q000294:innervation* / Q000503:physiopathology*; D008297:Male; D009619:Nociceptors / Q000503:physiopathology*; D010146:Pain / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000503:physiopathology*
chemical_list: D002395:Catecholamines