The Changes of GABA transporters (GAT-1 and GAT-3) and GABAA Receptor α1 subunit Expression in the Spinal Cord after Peripheral Nerve injury: Effect of GABAA Receptor Stimulation and Glial Inhibition

Regarding the loss of spinal GABAergic inhibition in neuropathic state,we assayed for protein level of the GABA transporters (GAT-1 and GAT-3) and GABAA receptor α1subunit in male wistar rats with chronic constriction injury (CCI) model of neuropathic pain (Bennett method,1988).We also examined whether the GABAA receptor agonist muscimol and glial inhibitor pentoxifylline would modify behavioral tests and also could modulate the level of GABA transporters.Behavioral tests (plantar test and Von Frey) were performed one day before surgery and then on days 1,4,7 and 14 after surgery in sham and CCI groups.In group that received muscimol (2 mg/kg) on day 14 after CCI, behavioral tests were examined 30 minutes after drug administration on the same day.Pentoxifylline (30 mg/kg daily) was administered one day before neuropathy and then daily to 14 days after CCI.Behavioral tests were performed 30 minutes after pentoxifylline administration only on day 14.GABA transporters and α1 subunit of GABAA receptor expression were detected by Western blotting.CCI was associated with a considerable reduction in GAT-1 and GAT-3 protein level in the lumbar spinal cord of CCI animals but the level of GABAA receptor α1 subunit did not change in CCI group compared to sham group.Both muscimol and pentoxifylline could reduce hyperalgesia and allodynia but could not modulate the level of GABA transporters.The results showed the loss of GABAergic inhibitory tone in neuropathic state and involvement of GAT-1 and GAT-3 in neuropathic pain development.Glial inhibition and GABAA receptor stimulation were effective in alleviating pain but could not be effective on transporters.