Modulation of visceral nociceptive pathways.
Increased sensitivity of visceral nociceptive pathways contributes to symptoms in an array of clinical gastrointestinal conditions, however, the search for a consistently effective pharmacological agent to treat these conditions remain elusive. Modulation of visceral nociceptive pathways can occur at peripheral, spinal and supra-spinal sites and a dizzying array of potential drug targets exists. Till date, only tricyclic anti-depressants (TCAs) such as amitriptyline and, more recently, selective serotonin reuptake inhibitors (SSRIs) such as citalopram have demonstrated convincing visceral anti-nociceptive properties and clinical benefit in a limited population of patients with visceral hypersensitivity. Unfortunately, there is an incomplete understanding of the receptors and/or primary site of action at which these compounds exert their effects and significant side effects are often encountered. There is a continuing and concerted effort underway to develop target-specific visceral analgesic/anti-hyperalgesic compounds and the aim of this article is to provide a concise update on the most recent advances in this area.
Hobson
Anthony R
AR
GI Discovery Medicine and Clinical Development, Neurology & GI CEDD, GlaxoSmithKline R&D Ltd., New Frontiers Science Park, Third Avenue, Harlow, Essex, United Kingdom. anthony.r.hobson@gsk.cm
Aziz
Qasim
Q
D062565:Acid Sensing Ion Channels; D000818:Animals; D019382:Human Growth Hormone / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D008565:Membrane Proteins / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000187:drug effects; D009434:Neural Pathways / Q000187:drug effects*; D010146:Pain / Q000503:physiopathology*; D019936:Probiotics; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects; D044462:Receptors, Proteinase-Activated / Q000187:drug effects; D015222:Sodium Channels / Q000187:drug effects; D050916:TRPV Cation Channels / Q000187:drug effects
D062565:Acid Sensing Ion Channels; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018341:Receptors, Adrenergic, alpha-2; D044462:Receptors, Proteinase-Activated; D015222:Sodium Channels; D050916:TRPV Cation Channels; D019382:Human Growth Hormone