趋化素受体 23 激动剂趋化素可减轻炎症性疼痛中表达神经激肽 1 受体的 lamina I 脊髓神经元的单突触 C 纤维传入。

BACKGROUND

Recent evidence has shown that the chemerin receptor 23 (ChemR23) represents a novel inflammatory pain target, whereby the ChemR23 agonists, resolvin E1 and chemerin, can inhibit inflammatory pain hypersensitivity, by a mechanism that involves normalisation of potentiated spinal cord responses. This study has examined the ability of the ChemR23 agonist, chemerin, to modulate synaptic input to lamina I neurokinin 1 receptor expressing (NK1R+) dorsal horn neurons, which are known to be crucial for the manifestation of inflammatory pain.

RESULTS

Whole-cell patch-clamp recordings from pre-identified lamina I NK1R+ neurons, in rat spinal cord slices, revealed that chemerin significantly attenuates capsaicin potentiation of miniature excitatory postsynaptic current (mEPSC) frequency, but is without effect in non-potentiated conditions. In tissue isolated from complete Freund's adjuvant (CFA) treated rats, chemerin significantly reduced the peak amplitude of monosynaptic C-fibre evoked excitatory postsynaptic currents (eEPSCs) in a subset of lamina I NK1R+ neurons, termed chemerin responders. However, chemerin did not alter the peak amplitude of monosynaptic C-fibre eEPSCs in control tissue. Furthermore, paired-pulse recordings in CFA tissue demonstrated that chemerin significantly reduced paired-pulse depression in the subset of neurons classified as chemerin responders, but was without effect in non-responders, indicating that chemerin acts presynaptically to attenuate monosynaptic C-fibre input to a subset of lamina I NK1R+ neurons.

CONCLUSIONS

These results suggest that the reported ability of ChemR23 agonists to attenuate inflammatory pain hypersensitivity may in part be due to a presynaptic inhibition of monosynaptic C-fibre input to lamina I NK1R+ neurons and provides further evidence that ChemR23 represents a promising inflammatory pain target.

背景

最近的证据表明，趋化素受体 23（ChemR23）是一种新的炎症性疼痛靶点，趋化素受体 23 激动剂，如 resolvin E1 和趋化素，通过使脊髓反应增强正常化的机制，可抑制炎症性疼痛过敏。本研究检查了趋化素受体 23 激动剂趋化素调节表达神经激肽 1 受体（NK1R+）背角神经元的突触传入的能力，已知这些神经元对炎症性疼痛的表现至关重要。

结果

在大鼠脊髓切片中，从预先鉴定的 lamina I NK1R+神经元进行全细胞膜片钳记录，发现趋化素显著减弱辣椒素对微小兴奋性突触后电流（mEPSC）频率的增强作用，但在未增强的条件下没有作用。在完全弗氏佐剂（CFA）处理的大鼠分离的组织中，趋化素显著降低了 lamina I NK1R+神经元中一部分称为趋化素反应神经元的单突触 C 纤维诱发的兴奋性突触后电流（eEPSC）的峰值幅度。然而，趋化素并未改变对照组织中单突触 C 纤维 eEPSC 的峰值幅度。此外，在 CFA 组织中的成对脉冲记录表明，趋化素显著降低了分类为趋化素反应神经元的亚组的成对脉冲抑制，而在非反应神经元中没有作用，表明趋化素在突触前作用以减弱 lamina I NK1R+神经元的单突触 C 纤维输入。