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Upregulation of the GABA-transporter GAT-1 in the spinal cord contributes to pain behaviour in experimental neuropathy.
Neurosci Lett 2008; 444(1):112-5NL

Abstract

Sciatic nerve ligation in rats (chronic constriction injury (CCI)) induces signs and symptoms that mimic human conditions of neuropathy. The central mechanisms that have been implicated in the pathogenesis of neuropathic pain include increased neuronal excitability, possibly a consequence of decreased availability of spinal GABA. GABA availability is regulated by the presence of the GABA-transporters (GATs). This study investigates the dorsal horn expression of the transporter GAT-1 and its functional involvement towards pain behaviour in the CCI model. Male Lewis rats (total n=37) were subjected to CCI or to a sham procedure. A sub-group of animals was treated with the GAT-1 antagonist NO-711. Behavioural testing was performed pre-surgery and at 7 days post-surgery. Testing included evaluation of mechanical allodynia using Von Frey filaments, thermal allodynia with a hot-plate test and observational testing of spontaneous pain behaviour. Subsequently, spinal protein expression of GAT-1 was assessed by Western blotting. Animals were sacrificed 7 days following surgery. CCI markedly increased mechanical and thermal allodynia and spontaneous pain behaviour after 7 days, while the sham procedure did not. GAT-1 was increased in spinal cord homogenates compared contralateral to the ligation side after 7 days. NO-711 treatment significantly reduced all tested pain behaviour. These data provide evidence for possible functional involvement of GAT-1 in the development of experimental neuropathic pain. The latter can be derived from observed analgesic effects of early treatment with NO-711, a selective GAT-1 inhibitor. The obtained insights support the clinical employment of GAT-1 inhibitors to treat neuropathic pain.

Authors+Show Affiliations

Department of Neurosurgery, University Hospital Maastricht, Maastricht, The Netherlands. daemenmarc@gmail.comNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18694804

Citation

Daemen, Marc A R C., et al. "Upregulation of the GABA-transporter GAT-1 in the Spinal Cord Contributes to Pain Behaviour in Experimental Neuropathy." Neuroscience Letters, vol. 444, no. 1, 2008, pp. 112-5.
Daemen MA, Hoogland G, Cijntje JM, et al. Upregulation of the GABA-transporter GAT-1 in the spinal cord contributes to pain behaviour in experimental neuropathy. Neurosci Lett. 2008;444(1):112-5.
Daemen, M. A., Hoogland, G., Cijntje, J. M., & Spincemaille, G. H. (2008). Upregulation of the GABA-transporter GAT-1 in the spinal cord contributes to pain behaviour in experimental neuropathy. Neuroscience Letters, 444(1), pp. 112-5. doi:10.1016/j.neulet.2008.08.001.
Daemen MA, et al. Upregulation of the GABA-transporter GAT-1 in the Spinal Cord Contributes to Pain Behaviour in Experimental Neuropathy. Neurosci Lett. 2008 Oct 17;444(1):112-5. PubMed PMID: 18694804.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Upregulation of the GABA-transporter GAT-1 in the spinal cord contributes to pain behaviour in experimental neuropathy. AU - Daemen,Marc A R C, AU - Hoogland,Govert, AU - Cijntje,Jean-Maurice, AU - Spincemaille,Geert H, Y1 - 2008/08/05/ PY - 2008/05/14/received PY - 2008/07/23/revised PY - 2008/08/01/accepted PY - 2008/8/13/pubmed PY - 2009/2/4/medline PY - 2008/8/13/entrez SP - 112 EP - 5 JF - Neuroscience letters JO - Neurosci. Lett. VL - 444 IS - 1 N2 - Sciatic nerve ligation in rats (chronic constriction injury (CCI)) induces signs and symptoms that mimic human conditions of neuropathy. The central mechanisms that have been implicated in the pathogenesis of neuropathic pain include increased neuronal excitability, possibly a consequence of decreased availability of spinal GABA. GABA availability is regulated by the presence of the GABA-transporters (GATs). This study investigates the dorsal horn expression of the transporter GAT-1 and its functional involvement towards pain behaviour in the CCI model. Male Lewis rats (total n=37) were subjected to CCI or to a sham procedure. A sub-group of animals was treated with the GAT-1 antagonist NO-711. Behavioural testing was performed pre-surgery and at 7 days post-surgery. Testing included evaluation of mechanical allodynia using Von Frey filaments, thermal allodynia with a hot-plate test and observational testing of spontaneous pain behaviour. Subsequently, spinal protein expression of GAT-1 was assessed by Western blotting. Animals were sacrificed 7 days following surgery. CCI markedly increased mechanical and thermal allodynia and spontaneous pain behaviour after 7 days, while the sham procedure did not. GAT-1 was increased in spinal cord homogenates compared contralateral to the ligation side after 7 days. NO-711 treatment significantly reduced all tested pain behaviour. These data provide evidence for possible functional involvement of GAT-1 in the development of experimental neuropathic pain. The latter can be derived from observed analgesic effects of early treatment with NO-711, a selective GAT-1 inhibitor. The obtained insights support the clinical employment of GAT-1 inhibitors to treat neuropathic pain. SN - 0304-3940 UR - https://www.unboundmedicine.com/medline/citation/18694804/Upregulation_of_the_GABA_transporter_GAT_1_in_the_spinal_cord_contributes_to_pain_behaviour_in_experimental_neuropathy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(08)01084-7 DB - PRIME DP - Unbound Medicine ER -