Effect Of Propofol On Spinal Cord GABA_A, NMDA, μ-opioid Receptor Expression

Background and ObjectivePropofol is an ultrashort-acting intravenous anesthetic agents. It has a rapid onset,short duration of action,rapid recovery and easy control,the advantages if fewer side effect.Since 1986,clinical application since the scope of its use more widely.The beginning in the operating room for the start of the induction of anesthesia, maintain anesthesia during surgery, Now widly used in a variety of short outpatient anesthesia and various endoscopic examination. For example:an painless induced abortion painless gastroscope,painless colonoscopy et al.In past,there is no analgesic effect of propofol in pharmacology. Anker-moller E et al studies suggested that sub-sleep dose of propofol had analgesic effect in 1991.Some studies had shown that dose of either sleep or sub-sleep dose of propofol also had analgesic.Some research suggested that not only do not had the analgesic effect of propofol may also lead to hyperalgesia. Propofol had analgesic effects in that study,propofol at the spinal cord for the antinociceptive mechanism of the analgesic effect,because different methods,different disturbance factors and the limitations of the study led to results were different.Propofol has a proven analgesic effect in the study,is the application of some of the specific receptor antagonist or agonnist used to indirectly prove the analgesic effect of propofol in the spinal cord.Neurons in the spinal cord of biological activities, a dozen of the neurotransmitter involved in the process of sponial cord in the transmission of information.Noxious stimulation in the process of information transmission,can promote the role of the main neurotransmitter glutamate, p substance,there are inhibitory effect of opiod peptides in the main neurotransmitter,GABA,Glycine.In the spinal cord,there is a large variety of synapse formation of neurons.Role in the mechanisim of anesthetic drugs,the prominent theory is very important.The doctrine that the role of anesthsia drugs mainly affect synaptic transmission;enhancement and suppression of inhibitory transmission prominent excitatory synaptic transmission. GABA is the main spinal inhibitory neurotransmitter, and its wide distribution in the spinal dorsal horn layerⅡandⅡⅢdistribution of wealth.When the GABAreceptor is activatec,can lead to neuronal membrane cl- permeability incteased,so that the neuron was depolarized.Afferent terminal excitability resulting in the release of neurotransmitters disappear in primary afferent fibersmotor neuron synaptic inhibition produced.NMDA receptor activtion causes the release of excitatory neuritransmitters,NMDA receptors are widely distributed in the spinal cord,caused by peripheral inflammation when oersistent noxious stimulation of peripheral nerve fibers to pass through to the posterior horn of the spinal cord,can cause excitatory amino acids(mainly as glutamic and aspartic)release,excitatory amino acid and throygh the activation of NMDAR.Glia in the spinal cord area,spinal trigeminal nucleus of the glieal end there are also opioid recepor distribution,these structures are important pain impulse to convert the incoming central station,the introduction of the pain inpulse.Existing research results show that propofol peripheral antinociceptive targets may be the primary rolr of the spinal cord,but its role in the specific mechanism is unclear.In this study,peripheral administration,whether the analgesic effect of propofol,and in the spinal cord GABA,NMDA,opioid receptors in spinal analgesia with propofol in the relationship.Thus,better guide the clinical application.Procedure Selected 32 adult male SD rats,weighing 220-250g.Randomly divided into 5:Controlgroup(NS,n=8),normalsaline(NS,n=8),propofo5mg/Kg(Pl,n=8),propofol30 mg/Kg(P2,n=8),propofo100mg/Kg(P3,n=8).Does not deal with control group, received normal 0.9% saline,5mg/Kg propofol,30mg/Kg propofol,100mg/Kg propofol.5 min later 5% formalin 100μl was injected subcutaneously into the planta region of right hindpaw.Observation sfter the first phase of formalin injection (O～10min)and the second phase (10-60min) every 5 minutes total time as a rat licking behavior indicators.Rats were killed after 2 hours,take 4 to 6 lumbar spinal cord,spinal cord dorsal horn GABAA,NMDA,μ-opioid receptor protein levels.Result1.Each group were licking the cumulative time for camparison:NS,P1,P2, P3group licking cumulative time was significantly longer than the C group (p<0.05); P1,P2,P3group licking cumulative time was significantly longer than the NS group (p<0.05);P2,P3group licking cumulative time was significantly longer than the P1 group (p<0.05); P3group licking cumulative time was significantly longer than the P2 group (p<0.05);2.Recepetor protein in spinal cord compared:GABAA protein compared: Compared with C group, NS,P1,P2,P3 group of GABAA protein to increase expression(P<0.05), Compared with NS group, P1,P2,P3 group of GABAA protein to increase expression(P<0.05), Compared with P1group,P2, P3 group of GABAA protein to increase expression(P<0.05), Compared with P2group,P3 group of GABAA protein to increase expression(P<0.05); NMDA protein compared:Compared with C group,NS,P1,P2,P3 group of NMDA protein to increase expression(P<0.05), Compared with NS group,P1,P2,P3 group of NMDA protein to decrease expression(P<0.05), Compared with P1,P2 group, P3 group of NMDA protein to decrease expression(P<0.05);μ-Opioid receptor protein compared:Compared with C group,NS,P1,P2,P3 group ofμ-opioid receptor protein to increase expression (P<0.05), Compared with NSgroup, P1,P2,P3 group of u-opioid receptor protein to increase expression(P<0.05), Compared with P1,P2group, P3 group ofμ-opioid receptor protein to increase expression(P<0.05). ConclusionSleep dose of propofol dose and sub-sleep has some analgesic effect and sode-dependent; Propofol analgesia and the spinal cord GABAAR,NMDAR andμ-opioid receptors.