Expression Of GABA And Its Receptors In The Rat Spinal Dorsal Horn Following Peripheral Inflammatory Hyperalgesia And The Influence Of Intrathecal GABA Receptors Agonists On Their Expression

Objective:Pain is a kind of feeling as a result of damage,disease or injury, the spinal cord which has lots of excitory and inhibitory neurotransmittes is the first area of central nerve system to manage nociception. -aminobutyric acid (GABA), one of the major inhibitory neurotransmittes in the spinal dorsal horn, acts on two receptor subtypes: ligand-gated channel GABAA receptor and GTP-binding protein-coupled GABAs receptor. They have been implicated in spinally mediated antinociception in acute pain models. In the current study, we will use the rats of formalin peripheral inflammatory pain model to study the GABA and its receptor system with spinal mechanism of pain by molecular biological technics.Method:There were forty-two male Spragne-Dawley rats (300-325g) which were subcutaneously injected of 5% formalin 50 1 into the right hindpaw to produce persistent nociception and were inserted a cathete through a small incision at centre of the atlanto-occipital membrane into the subarachnoid space 7-8 cm, ending at the L1 segment in the spinal subarachnoid space. Through the cathetes they were given muscimol and baclofen or the same volume of normal saline 10 minutes before or after administrated formalin respectively. Four other rats without any injection were used as control. Thebehavioral reaction was evaluated using the flinching count every 5 min after formalin injection described by Cowan and Berge. Rats were killed after 24h respectively.Then the lumbar spinal cords were cut into 6 m paraffin sections.Using the immunocytochemistry method, the changes of the number of GABA immunoreactive cells were observed,and the expression of the GABAA 3 and GABAB1 receptors mRNA in the spinal cord were determinded by in situ hybridization histochemistry.Result: All of the rats of peripheral formalin injected could be observed persistent flinching. At doses that did not affect motor function, intrathecally administrated muscimol and baclofen could decrease the flinch response during Phase 1 and Phase 2 of the formalin test, either pre- or post- given the two agonists.GABA immunoreactive cells, GABAA 3 and GABAB1 receptor mRNA would express in lumbar spinal cord dorsal root neurons of the normal rats.Twenty-four hours after formalin injection, we could find a significant increase of the GABA-immunoreactive cells in ipsilaterally spinal dorsal horn, GABAA 3 and GABAB1 receptor mRNA expression increased in bilateral dorsal horn, but their location in the spinal dorsal horn didn't change compared with control group. Intrathecally administrated muscimol and baclofen could depress all of the expression in dorsal lumbar spinal cord.Conclusion: GABA and its receptors's plasticity may play an important role in regulating the mediation and perception of the pain. GABAA and GABAB agonists have antinociceptive effect at the spinal cord level, the result support the theory of GABA system in modulating nociceptive input at spinal segmental level.