Impairment in spinal inhibition caused by quantitative alteration of GABAergic elements following
peripheral nerve injury has been postulated to mediate
neuropathic pain. In the present study, we tested whether
neuropathic pain could be induced or reversed by pharmacologically modulating spinal GABAergic activity, and whether quantitative alteration of spinal GABAergic elements after
peripheral nerve injury was related to the impairment of GABAergic inhibition or
neuropathic pain. To these aims, we first analyzed the
pain behaviors following the spinal administration of
GABA antagonists (1 microg
bicuculline/rat and 5 microg
phaclofen/rat), agonists (1 microg
muscimol/rat and 0.5 microg
baclofen/rat) or
GABA transporter (
GAT) inhibitors (20 microg
NNC-711/rat and 1 microg
SNAP-5114/rat) into naïve or neuropathic animals. Then, using Western blotting, PCR or immunohistochemistry, we compared the quantities of spinal
GABA, its synthesizing
enzymes (GAD65, 67) and its
receptors (GABA(A) and
GABA(B)) and transporters (GAT-1, and -3) between two groups of rats with different severity of
neuropathic pain following partial injury of tail-innervating nerves; the allodynic and non-allodynic groups. Intrathecal administration of
GABA antagonists markedly lowered tail-withdrawal threshold in naïve animals, and
GABA agonists or
GAT inhibitors significantly attenuated
neuropathic pain in nerve-injured animals. However, any quantitative changes in spinal GABAergic elements were not observed in both the allodynic and non-allodynic groups. These results suggest that although the impairment in spinal GABAergic inhibition may play a role in mediation of
neuropathic pain, it is not accomplished by the quantitative change in spinal elements for GABAergic inhibition and therefore these elements are not related to the generation of
neuropathic pain following
peripheral nerve injury.