Spinal GABA(A) and GABA(B) receptor pharmacology in a rat model of neuropathic pain

Anesthesiology. 2002 May;96(5):1161-7. doi: 10.1097/00000542-200205000-00020.


Background: This study tests the hypothesis that loss of spinal activity of gamma-aminobutyric acid (GABA) contributes to the allodynia and hyperalgesia observed after peripheral nerve injury.

Methods: Intrathecal catheters were implanted in male Sprague-Dawley rats. Antinociception was assessed by measuring withdrawal latency to immersion of the tail in a 52 degrees C water bath. Nerve injury was produced by ligation of the L5 and L6 spinal nerves. Testing was performed 4-14 days after spinal nerve ligation, when tactile allodynia and thermal hyperalgesia were established. Tactile allodynia was quantitated using the threshold to withdrawal of the hind paw on probing with von Frey filaments. Thermal hyperalgesia was quantitated using the latency to withdrawal of the hind paw from radiant heat. Motor function was tested using a rotarod apparatus.

Results: Spinal administration of the GABAA receptor antagonist bicuculline or the GABAB receptor antagonist phaclofen produced tactile allodynia and thermal hyperalgesia in normal rats. The GABAB receptor agonist baclofen, administered spinally, produced antinociception in the tail-flick test, whereas the GABAA receptor agonist isoguvacine did not. Isoguvacine and baclofen each reversed tactile allodynia and thermal hyperalgesia produced by spinal nerve ligation. Baclofen but not isoguvacine prolonged thermal withdrawal latency in nerve-injured rats beyond preoperative values. Baclofen but not isoguvacine impaired motor function.

Conclusions: Pharmacologic inhibition of intrinsic GABA tone in normal rats resulted in tactile allodynia and thermal hyperalgesia, consistent with the hypothesis being tested. Exogenous administration of GABA agonists reversed spinal nerve ligation-induced allodynia and hyperalgesia, also consistent with this hypothesis. Isoguvacine produced specific antihyperalgesic and antiallodynic effects, whereas assessment of the effects of baclofen was complicated by motor dysfunction. Spinal GABAA agonists may provide a specific therapy for neuropathic pain.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • GABA Agonists / pharmacology
  • GABA-A Receptor Agonists*
  • GABA-B Receptor Agonists*
  • Hot Temperature
  • Hyperalgesia / physiopathology
  • Injections, Spinal
  • Male
  • Motor Activity / drug effects
  • Pain / physiopathology*
  • Pain / psychology
  • Pain Measurement / drug effects
  • Peripheral Nervous System Diseases / physiopathology*
  • Peripheral Nervous System Diseases / psychology
  • Physical Stimulation
  • Psychomotor Performance / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord / drug effects*
  • Spinal Nerves / physiology
  • gamma-Aminobutyric Acid / physiology


  • GABA Agonists
  • GABA-A Receptor Agonists
  • GABA-B Receptor Agonists
  • gamma-Aminobutyric Acid