title: The sodium channel auxiliary subunits beta1 and beta2 are differentially expressed in the spinal cord of neuropathic rats.
abstract: Neuropathic pain is thought to arise from ectopic discharges at the site of injury within the peripheral nervous system, and is manifest as a general increase in the level of neuronal excitability within primary afferent fibres and their synaptic contacts within the spinal cord. Voltage-activated Na+ channel blockers such as lamotrigine have been shown to be clinically effective in the treatment of neuropathic pain. Na+ channels are structurally diverse comprising a principal a subunit (of which there are variable isoforms) and two auxiliary subunits termed beta1 and beta2. Both beta subunits affect the rates of channel activation and inactivation, and can modify alpha subunit density within the plasma membrane. In addition, these subunits may interact with extracellular matrix molecules to affect growth and myelination of axons. Using in situ hybridization histochemistry we have shown that the expression of the beta1 and beta2 subunits within the dorsal horn of the spinal cord of neuropathic rats is differentially regulated by a chronic constrictive injury to the sciatic nerve. At days 12-15 post-neuropathy, beta1 messenger RNA levels had increased, whereas beta2 messenger RNA levels had decreased significantly within laminae I, II on the ipsilateral side of the cord relative to the contralateral side. Within laminae III-IV beta2 messenger RNA levels showed a small but significant decrease on the ipsilateral side relative to the contralateral side, whilst expression of beta1 messenger RNA remained unchanged. Thus, differential regulation of the individual beta subunit types may (through their distinct influences on Na+ channel function) contribute to altered excitability of central neurons after neuropathic injury.
authors: Department of Preclinical Veterinary Sciences, The Royal (Dick) School of Veterinary Studies, The University of Edinburgh, Summerhall, UK.
authors: G
authors: G
authors: Blackburn-Munro
authors: S M
authors: SM
authors: Fleetwood-Walker
mesh_terms: D000818:Animals; D003080:Cold Temperature; D005727:Ganglia, Spinal / Q000187:drug effects / Q000503:physiopathology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006930:Hyperalgesia / Q000235:genetics / Q000503:physiopathology*; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D015640:Ion Channel Gating / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics; D013116:Spinal Cord / Q000378:metabolism* / Q000503:physiopathology; D013779:Tetrodotoxin / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000096:biosynthesis / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D015222:Sodium Channels; D014660:Vasoactive Intestinal Peptide; D013779:Tetrodotoxin