Are Spinal GABAergic Elements Related to the Manifestation of Neuropathic Pain in Rat?

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 microgram bicuculline/rat and 5 microgram phaclofen/rat), agonists (1 microgram muscimol/rat and 0.5 microgram baclofen/rat) or GABA transporter (GAT) inhibitors (20 microgram NNC-711/rat and 1 microgram SNAP-5114/rat) into naive 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 (GABAA and GABAB) 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 naive 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.

Effects of kainic Acid-induced seizures on GABA and GABA transporter in the cerebellum of the rat / 대한해부학회지

The effects of kainic acid-induced seizures on GABA and GABA transporter in the rat cerebellum were examined by means of immunohistochemical and Western blot methods. Immunocytochemical analysis showed that kainic acid-induced seizures led to a decreased immunoreactivity for GABA to 3 weeks after seizures with an slight increase in the immunoreactivity of cerebellum 24 h after treatment. Immunoreactivities of GABA transporters, GAT-1 and GAT-3 which are localized neurons and astrocytes, were increased at 24 and 48h and after that weak immunoreactivites for GABA transporters were shown in the cerebellar tissues. Our results indicate that kainic acid-induced seizures exerts specific effects on GABA contents and the GABA transporters in the cerebellum and a decrease of GABA contents might not always associated with the decrease in the number of GABA transporters in the rat cerebellum.

Expression of GABA Transporters in the Rat's Olfactory Bulb during Development

Developmental changes in the expression of two GABA (gamma-aminobutyric acid) transporter proteins, GAT-1 and GAT-3, in the olfactory bulb of embryonic and postnatal rats were examined with immunocytochemistry using antisera against GAT-1 and GAT-3. The expression and localization of GAT-1 and GAT-3 showed distinct temporal patterns during olfactory bulb development. GAT-1 immunoreactivity appeared weakly in most likely growing axons of the presumptive glomerular layer from embryonic day 18 and increased during the first postnatal week. In contrast, GAT-3 immunoreactivity, first detected at E16, was found in radial glial cell fascicles and was replaced by what were likely astroglial cells postnatally. At P7, GAT-1 and GAT-3 immunoreactivities reached the adult pattern i.e., GAT-1 immunoreactivity was observed in the labeled punctate structures in all layers of the olfactory bulb except the nerve fiber layer, while GAT-3 immunoreactivity was observed in the astroglial processes of all layers of the olfactory bulb. Our results suggest that GABA transporters, especially GAT-3, play important roles in regulating the GABA levels of developing olfactory bulbs.