TRPV1 receptor inhibition decreases CCL2-induced hyperalgesia

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• 作者：Diana Spicarova ^{dianaspicarova@biomed.cas.cz" class="auth_mail} ; Pavel Adamek ^{adamek@biomed.cas.cz" class="auth_mail} ; Nataliia Kalynovska ^{kalynovska@biomed.cas.cz" class="auth_mail} ; Petra Mrozkova ^{skya@biomed.cas.cz" class="auth_mail} ; Jiri Palecek ; ^{palecek@biomed.cas.cz" class="auth_mail}
• 关键词：Pain ; Spinal cord ; Synaptic transmission ; CCL2 ; TRPV1 ; EPSC
• 刊名：Neuropharmacology
• 出版年：June, 2014
• 年：2014
• 卷：81
• 期：Complete
• 页码：75-84
• 全文大小：1294 K

文摘

Modulation of nociceptive synaptic transmission in the spinal cord is implicated in the development and maintenance of several pathological pain states. The chemokine CCL2 (C-C motif ligand 2) was shown to be an important factor in the development of neuropathic pain after peripheral nerve injury. In our experiments we have studied the effect of CCL2 application and TRPV1 (transient receptor potential vanilloid 1) receptor activation on nociceptive signaling and the modulation of synaptic transmission. Intrathecal drug application in behavioral experiments and patch-clamp recordings of spontaneous, miniature and dorsal root stimulation-evoked excitatory postsynaptic currents (sEPSCs, mEPSCs, eEPSCs) from superficial dorsal horn neurons in acute rat spinal cord slices were used. The intrathecal application of CCL2 induced thermal hyperalgesia and mechanical allodynia, while pretreatment with the TRPV1 receptor antagonist SB366791 diminished the thermal but not the mechanical hypersensitivity. Patch-clamp experiments showed an increase of sEPSC and mEPSC (124.5聽卤聽12.8% and 161.2聽卤聽17.3%, respectively) frequency in dorsal horn neurons after acute CCL2 application. This CCL2-induced increase was prevented by SB366791 pretreatment (89.4聽卤聽6.0%, 107.5聽卤聽14.2%). CCL2 application increased the amplitude of eEPSCs (188.1聽卤聽32.1%); this increase was significantly lower in experiments with SB366791 pretreatment (120.8聽卤聽17.2%). Our results demonstrate that the activation of spinal TRPV1 receptors plays an important role in the modulation of nociceptive signaling induced by CCL2 application. The mechanisms of cooperation between the CCL2 activated receptors and TRPV1 receptors on the central branches of primary afferent fibers may be especially important during different pathological pain states and need to be further investigated.