| BackgroundThe pain usually due to a variety of noxious stimulation. All kinds of physical andchemical factors can become noxious stimuli that cause pain appeared. In injury stateor inflammation state, cells and tissue will released a variety of cytokines, such asIL-1, potassium,5-serotonin, acetylcholine, bradykinin, histamine and otherbioactive substances into the extracellular fluid. All of that can also cause pain andhyperalgesia. As Nociceptors, free nerve endings distributed in the body skin and avariety of organizations can transform different forms of noxious stimuli into a certaintype of the nerve impulse. And the impulse transmited by the myelinated(Aδ-fibers)and unmyelinated(C-fibers) afferent nerve fibers, from dorsal root ganglion to theposterior horn of the spinal cord and then through the contralateral ventrolateralfuniculus to the thalamus and cerebral cortex, other brain areas, and finally lead topain perception and response.The mechanisms of postoperative hyperalgesia is complex, and there is a closerelationship with peripheral and central sensitization. Inflammatory factors effect onperipheral nociceptors and change the excitability and sensitivity of nociceptor tocause the peripheral hyperalgesia. As persistent noxious stimulation, gene expression and many other mechanisms leading to the dorsal horn of spinal cord and brainsensitization.Previous studies of hyperalgesia focused on afferent signals and excitotoxicneuronal functional up-regulation. GABA (gamma-Aminobutyric, GABA) andglycine (Glycine, Gly) receptor plays a important role in transduction and inhibitionof pain. As the key factor of GABA and glycine receptor, chloride ion channel beganto be concerned and considered to be a new target for treatment of pain recently. Andas main chloride balance regulatory protein of nerve tissue, Na~+K~+2Cl~-cotransport1has become the hotspot of pain mechanism research.At present, scholars in capsaicin pain model, formalin pain model, and arthritismodels have confirmed that Na~+K~+2Cl~-cotransport1plays an important role in theformation and maintenance of hyperalgesia. But there is less report about the role ofNKCC1in the formation and maintenance of acute pain. Therefore this study using arat model of incisional pain, To observe the change of postoperative behavior and thenumber of the NKCC1positive cells affected by intrathecal bumetanide. To assess therole of intrathecal injection of bumetanide in rats with postoperative hyperalgesia,and to explore its possible mechanism,and finally provide a theoreticalbasis for clinical application.MethodsA total of One hundred and thirty-five male SD rats (provided by theExperimental Animal Center of Guangdong Province) were divided randonfly intofour groups. Control group (no treatment n=27), intrathecal injection group(intrathecal injection of bumetanide100μg, n=36), operation group (incision on theright planter surface, n=36), experimental group(intrathecal injection of bumetanide100μg and then incision on the right planter surface, n=36). Pain behavior wasassessed by the cumulative pain score, response latency of the hind paw to radiantthermal and the withdrawal threshold to von Frey filament stimulation intensity. Theexpression of NKCC1in Dorsal root ganglion were assessed by immunofluorescence Results1.Changes in thermal pain thresholdThe basis of thermal pain threshold is no significant difference (P>0.05).Compared with the control group, the thermal pain threshold of the rats inthe injection group is increasing in the two hours and the four hours after injection(P<0.05). Compared with the control group, the thermal pain threshold of the rats inthe operation group and the experimental group is reduce (P<0.05), and operationgroup is significantly lower than the experimental group (P<0.05).2. Changes in mechanical pain thresholdThe basis of mechanical pain threshold is no significant difference (P>0.05).Compared with the control group, the mechanical pain threshold of the rats inthe injection group is increasing in the two hours after injection (P<0.05).Compared with the control group, the mechanical pain threshold of the rats in theoperation group and the experimental group is reduce (P<0.05), and operation groupis significantly lower than the experimental group (P<0.05).3. Cumulative pain scoreThe Cumulative pain score of the rats in the injection group and the controlgroup is no significant difference in each observed point (P>0.05).Compared with the control group, the Cumulative pain score of the rats in theoperation group and the experimental group is increase (P<0.05), and operation groupwas significantly higher than the experimental group (P<0.05).4. Na~+K~+2Cl~-Cotransport1positive cells countCompared with the control group, the Na~+K~+2Cl~-Cotransport1positive cellscount of the rats in the injection group is no significant difference in each observedpoint (P>0.05). Compared with the control group, the Na~+K~+2Cl~-Cotransport1positive cells count of the rats in the operation group and the experimental group isincrease (P<0.01), and operation group is significantly higher than the experimentalgroup (P<0.01). Conclusions1. Intrathecal injection of bumetanide can improve the thermal threshold of rat inincision model.2. Intrathecal injection of bumetanide can improve the mechanical painthreshold of rat in incision model.3. Intrathecal injection of bumetanide can improve the pain behavior of rat inincision model, and reduce the cumulative score of pain.4. Intrathecal injection of bumetanide can reduce the expression of Na~+K~+2Cl~-Cotransport1in DRG, prompting the bumetanide can antagonistic hypersensitivity,and the antinociceptive effect of bumetanide might be concerned with inhibition ofNKCC15. NKCC1play an important role in the formation and maintenance of acutehyperalgesia... |
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