Transient receptor potential vanilloid 1 (TRPV1) channels contribute to the development of several chronic pain states and represent a possible therapeutic target in many painful disease treatment. Proinflammatory mediator bradykinin (BK) sensitizes TRPV1, whereas noxious peripheral stimulation increases BK level in the spinal cord. Here, we investigated the involvement of spinal TRPV1 in thermal and mechanical hypersensitivity, evoked by intrathecal (i.t.) administration of BK and an endogenous agonist of TRPV1, N-oleoyldopamine (OLDA), using behavioral tests and i.t. catheter implantation, and administration of BK-induced transient thermal and mechanical hyperalgesia and mechanical allodynia. All these hypersensitive states were enhanced by co-administration of a low dose of OLDA (0.42 µg i.t.), which was ineffective only under the control conditions. Intrathecal pretreatment with TRPV1 selective antagonist SB366791 prevented hypersensitivity induced by i.t. co-administration of BK and OLDA. Our results demonstrate that both thermal and mechanical hypersensitivity evoked by co-administration of BK and OLDA is mediated by the activation of spinal TRPV1 channels.

• Keywords
• OLDA, TRPV1, allodynia, bradykinin, hyperalgesia, spinal cord,
• MeSH
• Bradykinin MeSH
• Dopamine analogs & derivatives   MeSH
• Hyperalgesia metabolism   MeSH
• TRPV Cation Channels agonists   metabolism   MeSH
• Rats MeSH
• Spinal Cord metabolism   MeSH
• Rats, Wistar MeSH
• Injections, Spinal MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Bradykinin MeSH
• Dopamine MeSH
• TRPV Cation Channels MeSH
• N-oleoyldopamine MeSH Browser
• TRPV1 protein, mouse MeSH Browser

The mechanisms of inflammatory pain need to be identified in order to find new superior treatments. Protease-activated receptors 2 (PAR2) and transient receptor potential vanilloid 1 (TRPV1) are highly co-expressed in dorsal root ganglion neurons and implicated in pain development. Here, we examined the role of spinal PAR2 in hyperalgesia and the modulation of synaptic transmission in carrageenan-induced peripheral inflammation, using intrathecal (i.t.) treatment in the behavioral experiments and recordings of spontaneous, miniature and dorsal root stimulation-evoked excitatory postsynaptic currents (sEPSCs, mEPSCs and eEPSCs) in spinal cord slices. Intrathecal PAR2-activating peptide (AP) administration aggravated the carrageenan-induced thermal hyperalgesia, and this was prevented by a TRPV1 antagonist (SB 366791) and staurosporine i.t. pretreatment. Additionally, the frequency of the mEPSC and sEPSC and the amplitude of the eEPSC recorded from the superficial dorsal horn neurons were enhanced after acute PAR2 AP application, while prevented with SB 366791 or staurosporine pretreatment. PAR2 antagonist application reduced the thermal hyperalgesia and decreased the frequency of mEPSC and sEPSC and the amplitude of eEPSC. Our findings highlight the contribution of spinal PAR2 activation to carrageenan-induced hyperalgesia and the importance of dorsal horn PAR2 and TRPV1 receptor interactions in the modulation of nociceptive synaptic transmission.

• Keywords
• PAR2, TRPV1, inflammatory pain, nociception, peripheral inflammation, spinal cord, superficial dorsal horn, synaptic transmission, thermal hyperalgesia,
• MeSH
• Anilides pharmacology   MeSH
• Posterior Horn Cells drug effects   metabolism   physiology   MeSH
• Cinnamates pharmacology   MeSH
• Excitatory Postsynaptic Potentials MeSH
• Hyperalgesia etiology   metabolism   physiopathology   MeSH
• Carrageenan pharmacology   toxicity   MeSH
• TRPV Cation Channels antagonists & inhibitors   metabolism   MeSH
• Rats MeSH
• Miniature Postsynaptic Potentials MeSH
• Nociception MeSH
• Rats, Wistar MeSH
• Receptor, PAR-2 metabolism   MeSH
• Staurosporine pharmacology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anilides MeSH
• Cinnamates MeSH
• Carrageenan MeSH
• TRPV Cation Channels MeSH
• N-(3-methoxyphenyl)-4-chlorocinnamanilide MeSH Browser
• Receptor, PAR-2 MeSH
• Staurosporine MeSH
• Trpv1 protein, rat MeSH Browser