Capsaicin‐induced rapid neutrophil leukocyte activation in the rat urinary bladder microcirculatory bed

Abstract

Aims: This study was initiated to investigate the involvement of neutrophil leukocyte activation in neurogenic inflammation, a process also involved in human urinary pathologies, elicited in the rat urinary bladder by the local administration of capsaicin, the archetypal TRPV1 agonist. The contribution of afferent nerves and sensory neuropeptides to leukocyte activation in the urinary bladder microcirculatory bed was examined. Methods: Following a 15-min topical application of capsaicin (50 μM), leukocyteendothelial interactions were examined for an observation period of 45 min with intravital microscopy. Expression of adhesion molecules E-selectin and ICAM-1 implicated in these interactions was assessed by immunohistochemistry. Selective sensory denervation was performed by neonatal treatment with capsaicin. The role of the TRPV1 receptor and two sensory neuropeptides (CGRP and substance P [SP]) were studied using the selective antagonists capsazepine, CGRP 8-37 and RP67580, respectively. Results: Capsaicin induced rapid increases in leukocyte rolling and adhesion and increased the expression of E-selectin and ICAM-1 in the postcapillary venules.Sensory chemodenervation via capsaicin and also TRPV1 receptor antagonism effectively prevented these changes. A similar reduction was observed in leukocyte adhesion after topical application of CGRP 8-34 or RP67580, but only CGRP reduced the capsaicin-evoked leukocyte rolling. Conclusions: Topical application of capsaicin induces early neurogenically mediated cellular microcirculatory inflammatory reactions via the activation of the TRPV1 receptor and the release of CGRP and SP from sensory nerves in the bladder.Co-administration of SP and CGRP receptor antagonists may ameliorate microcirculatory inflammatory changes elicited by capsaicin in the urinary bladder.

Blocking SP/NK1R signaling improves spinal cord hemisection by inhibiting the release of pro-inflammatory cytokines in rabbits

“… 31 However, topical capsaicin promotes the release of SP from bladder sensory nerves. 32 In addition, capsaicin stimulated the release of SP from rabbit dorsal root ganglion (DRG) cells cultured in vitro in a time-dependent manner. 33 In this study, we used capsaicin to inhibit the expression of SP and observed that capsaicin improved SCH, however, the underlying mechanism needs to be further demonstrated.…”

Transient Receptor Potential Channels and Inflammatory Bowel Disease

“…In CD4 + T cells, TRPV1 was associated with T cell receptor (TCR) and facilitated TCR-induced Ca 2+ inflow (37), and the activity of CD4 + T cells was impaired via the inhibition of TRPV1 (38). The activation of TRPV1 was also reported to enhance leukocyte rolling and adhesion (39). These data indicated the possible pro-inflammatory properties of TRPV1 in immune cells.…”

Role of neurogenic inflammation in local communication in the visceral mucosa

“…Morphological analysis of the tissue from patients and animal models shows areas of leukocyte infiltration, edema, mast cells [25] and bladder wall glomerulations (‘pinpoint bleeding’) suggestive of fragile blood vessels (review [110]). A recent study using intravital microscopy methods imaged in vivo interactions between leukocytes and endothelial cell in the microcirculatory system following capsaicin application to the serosa surface of the bladder [111]. The experiments revealed a rapid (within 15 minutes after application) and long lasting (over 45 min) increase in the dynamic of leukocyte rolling and adhesion to endothelial cells accompanied by increased immunoreactivity for the adhesion proteins E-selectin and ICAM-1.…”

“…Leukocyte rolling was prevented by a CGRP receptor antagonist (CGRP8-34) but not by an NK1 receptor antagonist (RP67580), while the adhesion was prevented by blocking either CGRP or NK1 receptors. Taken together, these findings suggest that the dynamics and extent of neurogenic inflammation processes depend not only on the density of the TRPV1 positive fibers, but also on other factors such as the density of CGRP receptors and the expression of adhesion molecules in the tissue [111]…”