Radhakrishnan Rajan, Sluka Kathleen A
College of Pharmacy, University of Southern Nevada, South Jordan, UT, USA.
Neurosci Lett. 2009 Jul 3;457(3):141-5. doi: 10.1016/j.neulet.2009.03.086. Epub 2009 Apr 1.
Two injections of acidic saline into the gastrocnemius muscle produce long-lasting hyperalgesia that is initiated and maintained by changes in the rostroventromedial medulla (RVM). Potential underlying mechanisms could be increased release of excitatory neurotransmitters and/or reduced release of inhibitory neurotransmitters, in the RVM. We tested this hypothesis by measuring concentrations of aspartate, glutamate and glycine in response to the first and second injection of acidic saline and compared to intramuscular injections of normal saline using microdialysis with HPLC analysis. We show a significant increase in aspartate and glutamate during the second acidic saline injection compared to normal saline injections or the first injection of acidic saline. There were also long-lasting decreases in glycine concentrations in the RVM in response to both the first and second injection of acidic saline. It is possible that disinhibition after the first injection leads to long-lasting neuronal changes that allow a greater release of excitatory neurotransmitters after the second injection. We hypothesize that increased release of excitatory neurotransmitters in the RVM drives the release of excitatory neurotransmitters in the spinal cord, central sensitization and the consequent hyperalgesia.
向腓肠肌注射两次酸性盐水会产生持久的痛觉过敏，这种痛觉过敏由延髓头端腹内侧区（RVM）的变化引发并维持。潜在的机制可能是RVM中兴奋性神经递质释放增加和/或抑制性神经递质释放减少。我们通过测量首次和第二次注射酸性盐水后天冬氨酸、谷氨酸和甘氨酸的浓度来验证这一假设，并与使用微透析结合高效液相色谱分析的肌肉注射生理盐水进行比较。我们发现，与生理盐水注射或首次注射酸性盐水相比，第二次注射酸性盐水时天冬氨酸和谷氨酸显著增加。首次和第二次注射酸性盐水后，RVM中的甘氨酸浓度也会出现持久下降。首次注射后的去抑制作用可能会导致持久的神经元变化，从而使第二次注射后兴奋性神经递质释放增加。我们推测，RVM中兴奋性神经递质释放增加会驱动脊髓中兴奋性神经递质的释放、中枢敏化以及随之而来的痛觉过敏。
