Papers of the Week

Tumour necrosis factor (TNF) and kinins have been associated with neuropathic pain-like behaviour in numerous animal models. However, the way that they interact to cause neuron sensitisation remains unclear. This study assessed the interaction of kinin receptors and TNF receptor TNFR1/p55 in mechanical hypersensitivity induced by an intraneural (i.n.) injection of rm-TNF into the lower trunk of brachial plexus in mice. The i.n. injection of rm-TNF reduced the mechanical withdrawal threshold of the right forepaw from the 3rd to the 10th day after the injection, indicating that TNF1/p55 displays a critical role in the onset of TNF-elicited neuropathic pain. The connection between TNF1/p55 and kinin B and B receptors (BR and BR) was confirmed using both knockout mice and mRNAs quantification in the injected nerve, DRG and spinal cord. The treatment with the BR antagonist HOE 140 or with BR antagonist des-Arg-Leu-BK reduced both BK- and DABK-induced hypersensitivity. The experiments using kinin receptor antagonists and CPM inhibitor (thiorphan) suggest that BK does not only activate BR as an orthosteric agonist, but also seems to be converted into DABK that consequently activates BR. These results indicate a connection between TNF and the kinin system, suggesting a relevant role for BR and BR in the process of sensitisation of the central nervous systems by the cross talk between the receptor and CPM after i.n. injection of rm-TNF.