Protease-activated receptors 2 (PAR2) and transient receptor potential vanilloid 1 (TRPV1) receptors in the peripheral nerve endings are implicated in the development of increased sensitivity to mechanical and thermal stimuli, especially during inflammatory states. Both PAR2 and TRPV1 receptors are co-expressed in nociceptive dorsal root ganglion (DRG) neurons on their peripheral endings and also on presynaptic endings in the spinal cord dorsal horn. However, the modulation of nociceptive synaptic transmission in the superficial dorsal horn after activation of PAR2 and their functional coupling with TRPV1 is not clear. To investigate the role of spinal PAR2 activation on nociceptive modulation, intrathecal drug application was used in behavioural experiments and patch-clamp recordings of spontaneous, miniature and dorsal root stimulation-evoked excitatory postsynaptic currents (sEPSCs, mEPSCs, eEPSCs) were performed on superficial dorsal horn neurons in acute rat spinal cord slices. Intrathecal application of PAR2 activating peptide SLIGKV-NH2 induced thermal hyperalgesia, which was prevented by pretreatment with TRPV1 antagonist SB 366791 and was reduced by protein kinases inhibitor staurosporine. Patch-clamp experiments revealed robust decrease of mEPSC frequency (62.8 ± 4.9%), increase of sEPSC frequency (127.0 ± 5.9%) and eEPSC amplitude (126.9 ± 12.0%) in dorsal horn neurons after acute SLIGKV-NH2 application. All these EPSC changes, induced by PAR2 activation, were prevented by SB 366791 and staurosporine pretreatment. Our results demonstrate an important role of spinal PAR2 receptors in modulation of nociceptive transmission in the spinal cord dorsal horn at least partially mediated by activation of presynaptic TRPV1 receptors. The functional coupling between the PAR2 and TRPV1 receptors on the central branches of DRG neurons may be important especially during different pathological states when it may enhance pain perception.

• MeSH
• Hypersensitivity metabolism   pathology   MeSH
• Anilides pharmacology   MeSH
• Posterior Horn Cells drug effects   physiology   MeSH
• Behavior, Animal drug effects   MeSH
• Cinnamates pharmacology   MeSH
• Excitatory Postsynaptic Potentials drug effects   MeSH
• Hyperalgesia etiology   prevention & control   MeSH
• Protein Kinase Inhibitors pharmacology   MeSH
• TRPV Cation Channels antagonists & inhibitors   metabolism   MeSH
• Rats MeSH
• Patch-Clamp Techniques MeSH
• Spinal Cord metabolism   MeSH
• Synaptic Transmission physiology   MeSH
• Oligopeptides pharmacology   MeSH
• Rats, Wistar MeSH
• Receptor, PAR-2 agonists   metabolism   MeSH
• Staurosporine pharmacology   MeSH
• In Vitro Techniques MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anilides MeSH
• Cinnamates MeSH
• Protein Kinase Inhibitors MeSH
• TRPV Cation Channels MeSH
• N-(3-methoxyphenyl)-4-chlorocinnamanilide MeSH Browser
• Oligopeptides MeSH
• Receptor, PAR-2 MeSH
• seryl-leucyl-isoleucyl-glycyl-lysyl-valinamide MeSH Browser
• Staurosporine MeSH
• TRPV1 receptor MeSH Browser