Contribution of vanilloid receptors to the overt nociception induced by B₂ kinin receptor activation in mice

Abstract

1 The vanilloid receptor (TRPV1) is viewed as a molecular integrator of several nociceptive stimuli. In the present study, we have investigated the role played by TRPV1 in the nociceptive response induced by the peripheral activation of kinin B 2 receptor in mice. 2 The intraplantar (i.pl.) administration of bradykinin (BK) and the selective B 2 agonist Tyr 8 -BK, or the vanilloid agonists resiniferatoxin and capsaicin, into the mouse paw induced a dose-related overt nociception of short duration. The B 2 receptor antagonist Hoe 140 inhibited BK-induced, but not capsaicin-induced, nociceptive response. On the other hand, the TRPV1 antagonist capsazepine inhibited both capsaicin-and BK-mediated nociception. 3 Repeated injections of BK or capsaicin produced desensitization to their nociceptive response. Capsaicin desensitization greatly reduced BK-induced nociception, but in contrast, the desensitization to BK increased the capsaicin response. 4 Administration of low doses of capsaicin or acidified saline did not produce nociception when administered alone, but caused a pronounced effect when administered in association with a subthreshold dose of BK. Moreover, the degeneration of the subset of primary afferent fibers, sensitive to capsaicin, abolished both capsaicin-and BK-induced nociception. 5 The inhibition of phospholipase C (PLC), protein kinase C or phospholipase A 2 markedly decreased the nociception caused by BK, but not that of capsaicin. BK administration increased leukotriene B 4 levels in the injected paw. Likewise, BK-induced overt nociception was decreased by lipoxygenase (LOX) inhibition. 6 These results demonstrate that BK produces overt nociception mediated by TRPV1 receptor stimulation, via PLC pathway activation and LOX product formation.

TRPV1 Function in Mouse Colon Sensory Neurons Is Enhanced by Metabotropic 5-Hydroxytryptamine Receptor Activation

“…Several signaling pathways converge on TRPV1 to modulate its activity and, as shown in this and previous studies, alter neuron excitability (Bhave et al, 2003;Carr et al, 2003;Moriyama et al, 2003;Dai et al, 2004;Ferreira et al, 2004;Liu et al, 2004;Premkumar et al, 2004;Puntambekar et al, 2004). The potential role of TRPV1 in integrating different physical, chemical, and inflammatory signals and the comparatively high number of capsaicin-responsive colon sensory neurons support the relevance of this channel in sensation and visceral nociception.…”

Nociceptors Lacking TRPV1 and TRPV2 Have Normal Heat Responses

“…That TRPV1 is important in pathological states is further suggested by its ability to respond, and be potentiated by, multiple stimuli including those that are physical (heat and mechanical) and chemical (e.g., vanilloid compounds and acid). In addition, TRPV1 currents can be potentiated by interactions with G-coupled proteins like the bradykinin receptors (Shin et al, 2002;Sugiura et al, 2002;Carr et al, 2003;Ferreira et al, 2004) and the P2Y2 ATP receptor (Moriyama et al, 2003). It is also important to note that behavioral heat hyperalgesia induced by either complete Freund's adjuvant, carrageenan, or ATP is absent in TRPV1 Ϫ/Ϫ mice (although pretreatment responses are normal) (Caterina et al, 2000;Davis et al, 2000;Moriyama et al, 2003).…”

Cox-dependent fatty acid metabolites cause pain through activation of the irritant receptor TRPA1

“…Agonists were injected into the mouse paw as described (46,47). Immediately after injection, mice were placed in a Plexiglas chamber.…”