Upregulation of the GABA transporter GAT-1 in the gracile nucleus in the spared nerve injury model of neuropathic pain.
Neuropathic pain is a major health issue and is frequently accompanied by allodynia (painful sensations in response to normally non-painful stimulations), and unpleasant paresthesia/dysesthesia, pointing to alterations in sensory pathways normally dedicated to the processing of non-nociceptive information. Interestingly, mounting evidence indicate that central glial cells are key players in allodynia, partly due to changes in the astrocytic capacity to scavenge extracellular glutamate and gamma-aminobutyric acid (GABA), through changes in their respective transporters (EAAT and GAT). In the present study, we investigated the glial changes occurring in the dorsal column nuclei, the major target of normally innocuous sensory information, in the rat spared nerve injury (SNI) model of neuropathic pain. We report that together with a robust microglial and astrocytic reaction in the ipsilateral gracile nucleus, the GABA transporter GAT-1 is upregulated with no change in GAT-3 or glutamate transporters. Furthermore, [(3)H] GABA reuptake on crude synaptosome preparation shows that transporter activity is functionally increased ipsilaterally in SNI rats. This GAT-1 upregulation appears evenly distributed in the gracile nucleus and colocalizes with astrocytic activation. Neither glial activation nor GAT-1 modulation was detected in the cuneate nucleus. Together, the present results point to GABA transport in the gracile nucleus as a putative therapeutic target against abnormal sensory perceptions related to neuropathic pain.
Gosselin
Romain-Daniel
RD
Pain Research Unit, Department of Anesthesiology, University Hospital Center and University of Lausanne, Bugnon 46, 1011 Lausanne, Switzerland. Romain-Daniel.Gosselin@chuv.ch
Bebber
Damien
D
Decosterd
Isabelle
I
D027322:Amino Acid Transport System X-AG / Q000096:biosynthesis; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001692:Biological Transport; D027341:Excitatory Amino Acid Transporter 1 / Q000096:biosynthesis; D027342:Excitatory Amino Acid Transporter 2 / Q000096:biosynthesis; D050485:GABA Plasma Membrane Transport Proteins / Q000096:biosynthesis*; D008526:Medulla Oblongata / Q000378:metabolism*; D017628:Microglia / Q000378:metabolism; D010146:Pain / Q000209:etiology / Q000378:metabolism*; D010523:Peripheral Nervous System Diseases / Q000209:etiology / Q000378:metabolism*; D010543:Peroneal Nerve / Q000293:injuries; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000378:metabolism; D013979:Tibial Nerve / Q000293:injuries; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D027322:Amino Acid Transport System X-AG; D027341:Excitatory Amino Acid Transporter 1; D027342:Excitatory Amino Acid Transporter 2; D050485:GABA Plasma Membrane Transport Proteins; C493415:Slc6a1 protein, rat; C493417:Slc6a11 protein, rat; D005680:gamma-Aminobutyric Acid