神经激肽1和神经激肽2受体在急性炎症诱导的热痛觉过敏的发生和维持中的不同作用。

Differential roles of neurokinin 1 and neurokinin 2 receptors in the development and maintenance of heat hyperalgesia induced by acute inflammation.

作者信息

Sluka K A, Milton M A, Willis W D, Westlund K N

机构信息

Marine Biomedical Institute, University of Texas Medical Branch, Galveston 77555-1069, USA.

出版信息

Br J Pharmacol. 1997 Apr;120(7):1263-73. doi: 10.1038/sj.bjp.0701044.

DOI:10.1038/sj.bjp.0701044

PMID:9105701

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1564603/

Abstract

Following induction of acute inflammation by intraarticular injection of kaolin and carrageenan into the knee joint in rats, there was a significant decrease in the withdrawal latency to radiant heat applied to the paw (i.e. heat hyperalgesia), an increased joint circumference and increased joint temperature. 2. A neurokinin1 (NK1) receptor antagonist (CP-99,994, 10 mM) had no effect on the paw withdrawal latency when it was administered spinally through a microdialysis fibre before the induction of inflammation. Pretreatment with a NK2 receptor antagonist (SR48968, 1 mM) administered spinally through the microdialysis fibre prevented the heat hyperalgesia from developing in the early stages of the inflammation. 3. Post-treatment through the microdialysis fibre with the NK1 receptor antagonist (0.01-10 mM) was effective in reversing the heat hyperalgesia. In contrast, post-treatment spinally with the NK2 receptor antagonist (0.01-1 mM) had no effect on the heat hyperalgesia. The inactive stereoisomers of the NK1 receptor antagonist, CP100,263, or the NK2 receptor antagonist, SR48965, administered at the same doses, had no effect on the joint inflammation or the heat hyperalgesia. 4. Pretreatment systemically with the NK1 receptor antagonist (30 mg kg-1) had no effect on the heat hyperalgesia or pain-related behaviour ratings where 0 is none and 5 is non weight bearing and complete avoidance of limb contact. Pretreatment with a NK2 receptor antagonist (10 mg kg-1) systemically prevented the heat hyperalgesia and pain-related behaviour ratings from developing in the early stages of the inflammation. The inactive stereoisomers of NK1 receptor antagonist, CP100,263, or the NK2 receptor antagonist, SR48965, administered at the same doses, had no effect on the joint inflammation or the heat hyperalgesia. 5. Post-treatment systemically with either the NK1 (0.1-30 mg kg-1) or the NK2 (0.1-10 mg kg-1) receptor antagonist resulted in a dose-dependent reversal of the heat hyperalgesia. Pain-related behaviour ratings were reduced by post-treatment only with the NK1 receptor antagonist. The inactive stereoisomers of the NK1 receptor antagonist, CP100,263, or the NK2 receptor antagonist, SR48965, administered at the same doses, had no effect on the behavioural responses. 6. Direct pretreatment of the knee joint with either the NK1 (30 mg) or the NK2 (10 mg) receptor antagonist prevented the heat hyperalgesia from developing without affecting joint swelling. The inactive stereoisomers of the NK1 receptor antagonist, CP100,263, or the NK2 receptor antagonist, SR48965, administered at the same doses, had no effect on the joint inflammation or the heat hyperalgesia. 7. There appears to be a differential role for the spinal tachykinin receptors in the development and maintenance of the heat hyperalgesia associated with acute joint inflammation. The NK2 receptors appear to be activated early in the development of the heat hyperalgesia and NK1 receptors are involved in the maintenance of the heat hyperalgesia. 8. Peripherally, both NK1 and NK2 receptors are involved in the development of heat hyperalgesia and pain-related behaviour ratings induced by acute inflammation.

摘要

向大鼠膝关节内注射高岭土和角叉菜胶诱导急性炎症后，对爪子施加辐射热的缩爪潜伏期显著缩短（即热痛觉过敏），关节周长增加，关节温度升高。2. 神经激肽1（NK1）受体拮抗剂（CP - 99,994，10 mM）在炎症诱导前经微透析纤维脊髓给药时，对缩爪潜伏期无影响。经微透析纤维脊髓给予NK2受体拮抗剂（SR48968，1 mM）预处理可防止炎症早期热痛觉过敏的发展。3. 通过微透析纤维用NK1受体拮抗剂（0.01 - 10 mM）进行治疗后，可有效逆转热痛觉过敏。相比之下，脊髓给予NK2受体拮抗剂（0.01 - 1 mM）治疗后对热痛觉过敏无影响。相同剂量的NK1受体拮抗剂CP100,263或NK2受体拮抗剂SR48965的无活性立体异构体对关节炎症或热痛觉过敏无影响。4. 全身给予NK1受体拮抗剂（30 mg kg-1）预处理对热痛觉过敏或疼痛相关行为评分无影响（评分范围为0表示无疼痛，5表示无法负重且完全避免肢体接触）。全身给予NK2受体拮抗剂（10 mg kg-1）预处理可防止炎症早期热痛觉过敏和疼痛相关行为评分的发展。相同剂量的NK1受体拮抗剂CP100,263或NK2受体拮抗剂SR48965的无活性立体异构体对关节炎症或热痛觉过敏无影响。5. 全身给予NK1（0.1 - 30 mg kg-1）或NK2（0.1 - 10 mg kg-1）受体拮抗剂进行治疗后，可导致热痛觉过敏呈剂量依赖性逆转。仅NK1受体拮抗剂治疗后可降低疼痛相关行为评分。相同剂量的NK1受体拮抗剂CP100,263或NK2受体拮抗剂SR48965的无活性立体异构体对行为反应无影响。6. 直接用NK1（30 mg）或NK2（10 mg）受体拮抗剂预处理膝关节可防止热痛觉过敏的发展，且不影响关节肿胀。相同剂量的NK1受体拮抗剂CP100,263或NK2受体拮抗剂SR48965的无活性立体异构体对关节炎症或热痛觉过敏无影响。7. 脊髓速激肽受体在与急性关节炎症相关的热痛觉过敏的发生和维持中似乎具有不同作用。NK2受体似乎在热痛觉过敏发生早期被激活，而NK1受体参与热痛觉过敏的维持。8. 在周围组织中，NK1和NK2受体均参与急性炎症诱导的热痛觉过敏和疼痛相关行为评分的发生。