Xu I S, Grass S, Xu X J, Wiesenfeld-Hallin Z
Department of Medical Laboratory Sciences and Technology, Karolinska Institute, Huddinge University Hospital, Sweden.
Neuroscience. 1998 Aug;85(3):827-35. doi: 10.1016/s0306-4522(97)00676-3.
The effects of exogenous and endogenous galanin on spinal flexor reflex excitability was evaluated in rats one to eight days after the induction of inflammation by subcutaneous injection of carrageenan into the sural nerve innervation area. In normal rats, electrical stimulation of C-fibres in the sural nerve elicited a brisk reflex discharge. Conditioning stimulation of C-fibres (1/s) generated a gradual increase in reflex magnitude (wind-up), which was followed by a period of reflex hyperexcitability. Intrathecal galanin dose-dependently blocked reflex hyperexcitability induced by C-fibre conditioning stimulation whereas i.t. M-35, a high-affinity galanin receptor antagonist, moderately potentiated this effect. At one to three days after the injection of carrageenen, when inflammation was at its peak, the magnitude of the reflex was significantly increased and discharge duration became prolonged. However, wind-up and reflex hyperexcitability were significantly reduced. Furthermore, reduced reflex excitability during conditioning stimulation ("wind-down") and depression of the reflex were sometimes present, which are rarely observed in normal rats. Intrathecal galanin reduced hyperexcitability during inflammation, although its potency was weaker than in normals. However, the galanin receptor antagonist M-35 strongly enhanced wind-up and reflex hyperexcitability, similarly as in normal rats. The baseline flexor reflex, wind-up and C-fibre conditioning stimulation-induced facilitation were normalized four to eight days after carrageenan injection when signs of inflammation were diminishing. Interestingly, intrathecal galanin and M-35 failed to influence spinal excitability. The results suggest a complex functional plasticity in the role of endogenous galanin in mediating spinal excitability during inflammation. There appears to be an enhanced endogenous inhibitory control by galanin on C-afferent input during the peak of inflammation, which may explain the relative ineffectiveness of exogenous galanin. During the recovery phase there may be a reduction in galanin receptors, which may impair the action of endogenous and exogenous galanin. These results further support the notion that galanin is an endogenous inhibitory peptide in nociception.
通过向大鼠腓肠神经支配区域皮下注射角叉菜胶诱导炎症后1至8天，评估外源性和内源性甘丙肽对脊髓屈肌反射兴奋性的影响。在正常大鼠中，腓肠神经C纤维的电刺激引发快速的反射放电。C纤维的条件刺激（1次/秒）使反射幅度逐渐增加（后放电增强），随后是一段反射性兴奋性增强的时期。鞘内注射甘丙肽剂量依赖性地阻断了C纤维条件刺激诱导的反射性兴奋性增强，而鞘内注射高亲和力甘丙肽受体拮抗剂M-35则适度增强了这种效应。在注射角叉菜胶后1至3天，炎症处于高峰期时，反射幅度显著增加，放电持续时间延长。然而，后放电增强和反射性兴奋性增强显著降低。此外，有时会出现条件刺激期间反射兴奋性降低（“后放电减弱”）和反射抑制，这在正常大鼠中很少见。鞘内注射甘丙肽可降低炎症期间的兴奋性增强，尽管其效力比正常情况下弱。然而，甘丙肽受体拮抗剂M-35强烈增强后放电增强和反射性兴奋性增强，与正常大鼠情况类似。角叉菜胶注射后4至8天，当炎症迹象逐渐消失时，基线屈肌反射、后放电增强和C纤维条件刺激诱导的易化作用恢复正常。有趣的是，鞘内注射甘丙肽和M-35未能影响脊髓兴奋性。结果表明内源性甘丙肽在炎症期间介导脊髓兴奋性方面具有复杂的功能可塑性。在炎症高峰期，甘丙肽对C传入输入的内源性抑制控制似乎增强，这可能解释了外源性甘丙肽相对无效的原因。在恢复阶段，甘丙肽受体可能减少，这可能损害内源性和外源性甘丙肽的作用。这些结果进一步支持了甘丙肽是伤害感受中的内源性抑制肽这一观点。
