Department of Pharmacology, Graduate School of Biomedical & Health Sciences, Hiroshima University, Japan.
Department of Pharmacology, Graduate School of Biomedical & Health Sciences, Hiroshima University, Japan.
Biochem Biophys Res Commun. 2020 Dec 17;533(4):971-975. doi: 10.1016/j.bbrc.2020.09.113. Epub 2020 Sep 30.
Previous studies have reported that continuous infusion with substance P (SP) into rat dorsal striatum ameliorated both mechanical allodynia in both formalin-evoked transient inflammatory pain and neuropathic pain models. However, a role of striatal SP in persistent inflammatory pain has not been demonstrated. The current study examined the effect of continuous infusion of SP into the rat dorsal striatum by reverse microdialysis on persistent inflammatory pain induced by complete Freund's adjuvant (CFA). Intraplantar injection of CFA evoked both mechanical allodynia and paw edema 3 and 7 days post-injection. The continuous infusion of SP ameliorated the CFA-evoked mechanical allodynia, but not paw edema, 3 days after the CFA injection. This antinociceptive effect of SP was partially inhibited by co-infusion with the neurokinin-1 (NK1) receptor antagonist CP96345. Conversely, at 7 days both CFA-evoked mechanical allodynia and paw edema were not affected by SP treatment. To clarify why the effect of SP treatment on CFA-induced pain changed, we evaluated NK1 receptor protein levels at both time points. The NK1 receptor protein level was decreased at 7, but not 3, days post CFA injection. These data suggest that persistent inflammatory pain can downregulate the striatal NK1 receptor. The current study demonstrates that striatal SP-NK1 receptor pathway can exert antinociceptive effect only on the third days of inflammatory pain phase defined as an acute but not the 7 days defined as a subacute.
先前的研究报告表明，在大鼠背侧纹状体中持续输注 P 物质（SP）可改善福尔马林诱发的短暂炎症性疼痛和神经病理性疼痛模型中的机械性痛觉过敏。然而，纹状体 SP 在持续性炎症性疼痛中的作用尚未得到证实。本研究通过逆行微透析观察了 SP 持续输注到大鼠背侧纹状体对完全弗氏佐剂（CFA）诱导的持续性炎症性疼痛的影响。足底注射 CFA 可在注射后第 3 天和第 7 天引起机械性痛觉过敏和爪肿胀。SP 的持续输注可改善 CFA 诱发的机械性痛觉过敏，但不能改善 CFA 注射后第 3 天的爪肿胀。这种 SP 的镇痛作用被共输注神经激肽-1（NK1）受体拮抗剂 CP96345 部分抑制。相反，在第 7 天，CFA 诱发的机械性痛觉过敏和爪肿胀均不受 SP 治疗的影响。为了阐明 SP 治疗对 CFA 诱导的疼痛影响改变的原因，我们在两个时间点评估了 NK1 受体蛋白水平。NK1 受体蛋白水平在 CFA 注射后第 7 天而非第 3 天下降。这些数据表明，持续性炎症性疼痛可下调纹状体 NK1 受体。本研究表明，纹状体 SP-NK1 受体途径仅在炎症性疼痛阶段的第 3 天（定义为急性）而不是第 7 天（定义为亚急性）发挥镇痛作用。
