title: Chronic pain states: pharmacological strategies to restore diminished inhibitory spinal pain control.
abstract: Potentially noxious stimuli are sensed by specialized nerve cells named nociceptors, which convey nociceptive signals from peripheral tissues to the central nervous system. The spinal dorsal horn and the trigeminal nucleus serve as first relay stations for incoming nociceptive signals. At these sites, nociceptor terminals contact a local neuronal network consisting of excitatory and inhibitory interneurons as well as of projection neurons. Blockade of neuronal inhibition in this network causes an increased sensitivity to noxious stimuli (hyperalgesia), painful sensations occurring after activation of non-nociceptive fibers (allodynia), and spontaneous pain felt in the absence of any sensory stimulation. It thus mimics the major characteristics of chronic pain states. Diminished inhibitory pain control in the spinal dorsal horn occurs naturally, e.g., through changes in the function of inhibitory neurotransmitter receptors or through altered chloride homeo-stasis in the course of inflammation or nerve damage. This review summarizes our current knowledge about endogenous mechanisms leading to diminished spinal pain control and discusses possible ways that could restore proper inhibition through facilitation of fast inhibitory neurotransmission.
authors.affiliation: Institute of Pharmacology and Toxicology, University of Zurich, CH-8057 Zurich, Switzerland. zeilhofer@pharma.uzh.ch
authors.forename: Hanns Ulrich
authors.initials: HU
authors.lastname: Zeilhofer
authors.forename: Dietmar
authors.initials: D
authors.lastname: Benke
authors.forename: Gonzalo E
authors.initials: GE
authors.lastname: Yevenes
mesh_terms: D000818:Animals; D059350:Chronic Pain / Q000188:drug therapy*; D004195:Disease Models, Animal; D018682:GABA Agents / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology; D006801:Humans; D006930:Hyperalgesia / Q000188:drug therapy; D007249:Inflammation / Q000188:drug therapy; D009437:Neuralgia / Q000188:drug therapy; D059408:Pain Management / Q000379:methods*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects* / Q000503:physiopathology; D013131:Spine / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D018682:GABA Agents; D018684:Glycine Agents; D011963:Receptors, GABA-A