title: Spinal dis-inhibition in inflammatory pain.
abstract: Inflammatory diseases and neuropathic insults trigger signaling cascades, which frequently lead to intense and long-lasting pain syndromes in affected patients. Such pain syndromes are characterized not only by an increased sensitivity to painful stimuli (hyperalgesia), but also by a qualitative change in the sensory perception of other, tactile stimuli (allodynia) and the occurrence of spontaneous pain in the absence of any sensory input. Long-term potentiation (LTP)-like changes in synaptic transmission between nociceptive C-fibers and spino-periaqueductal grey projection neurons as well as a loss of inhibitory control by GABAergic and glycinergic spinal dorsal horn neurons have repeatedly been proposed as underlying principles. While considerable evidence supports a significant contribution of C-fiber LTP to hyperalgesia, such monosynaptic plasticity cannot explain the occurrence of allodynia and spontaneous pain. In this review, we focus on mechanisms of synaptic dis-inhibition in inflammatory pain and propose that pathologically heightened pain sensitivity can be reversed by restoring synaptic inhibition with drugs that target specific spinal GABAA receptor subtypes.
authors.affiliation: Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. zeilhofer@pharma.uzh.ch <zeilhofer@pharma.uzh.ch>
authors.forename: Hanns Ulrich
authors.initials: HU
authors.lastname: Zeilhofer
authors.forename: Ulrike B
authors.initials: UB
authors.lastname: Zeilhofer
mesh_terms: D000818:Animals; D006801:Humans; D007249:Inflammation / Q000150:complications; D008954:Models, Biological; D009433:Neural Inhibition; D010146:Pain / Q000209:etiology / Q000473:pathology*; D013116:Spinal Cord / Q000473:pathology / Q000503:physiopathology*; D013569:Synapses / Q000502:physiology