Blockade of TRPA1 with HC-030031 attenuates visceral nociception by a mechanism independent of inflammatory resident cells, nitric oxide and the opioid system.

TLDR: The participation of TRPA1 in visceral nociception and the involvement of nitric oxide, the opioid system and resident cells in the modulation of these channels are investigated.

About: This article is published in European Journal of Pain.The article was published on 2013-02-01 and is currently open access. It has received 32 citations till now. The article focuses on the topics: Nociception assay & Nociception.

Figures

Figure 3 Effect of resident peritoneal cell depletion on acetic acid, zymosan or misoprostol-induced writhing behaviour. Anaesthetized mice had the peritoneal cavity perfused (W) with sterile saline. A no-washed group was included (sham). Following this procedure, heparinized PBS was instilled i.p. to perform the peritoneal cell count (A). Sham (S) and washed (W) groups (n = 8) were injected with acetic acid, zymosan or misoprostol. The number of writhes was recorded for 30 min (B). The bars represent mean SEM. **p < 0.01 and ***p < 0.001 compared to sham group (unpaired Student’s t-test).

Figure 2 Antinociceptive effect of HC-030031 on acetic acid, zymosan and misoprostol-induced writhing behaviour. Swiss mice were pretreated with CMC, HC-030031, indomethacin or morphine 60 min previously the i.p. instillation of acetic acid (A), zymosan (B) or misoprostol (C). The bars represent mean SEM of the writhing behaviours expressed during 30 min (n = 8). *p < 0.05, **p < 0.01 and ***p < 0.001 versus vehicle group (ANOVA and Student Newman–Keul’s test).

Figure 1 Effect of HC-030031 on visceral nociception: study of nitric oxide and opioid system involvement. The nociceptive response was assessed by the electronic von Frey test before animal treatments and 12 h after ifosfamide administration (A, B) or 10 min following mustard oil injection (C, D). Visceral nociception was prevented by HC-030031, which was unaffected by L-arginine (B) or naloxone pretreatment (D). The bars represent mean SEM of 6–8 mice. Intensity of hyperalgesia was expressed in grams (g). *p < 0.01 compared to saline group, #p < 0.05 versus ifosfamide or mustard oil group, Y p < 0.05 in comparison with L-NAME or morphine (ANOVA and Student Newman–Keul’s test).

Table 1 HC-030031 does not protect against ifosfamide-induced haemorrhagic cystitis.

Figure 4 Effect of HC-030031 on paw PGE2-induced nociception. Vehicle or HC-030031 treated animals were injected with saline or PGE2 into the hind paw. Bars represent mean SEM time in seconds mice spent licking the injected paws. *p < 0.001 versus saline group and #p < 0.01 versus PGE2 group (ANOVA and Student Newman–Keul’s test).

Figure 5 HC-030031 does not cause ambulation impairment. Vehicle, HC-030031 or diazepam treated mice (n = 8) were observed for 4 min regarding the ambulation in the open-field arena. **p < 0.01 compared to vehicle group. The bars represent the mean SEM number of fields explored (ANOVA and Student Newman–Keul’s test).

Frequently asked questions

Q1. What have the authors contributed in "Blockade of trpa1 with hc-030031 attenuates visceral nociception by a mechanism independent of inflammatory resident cells, nitric oxide and the opioid system" ?

Therefore, the authors investigated the participation of TRPA1 in visceral nociception and the involvement of nitric oxide, the opioid system and resident cells in the modulation of these channels. Their findings suggest that the blockade of TRPA1 attenuates visceral nociception by a mechanism independent of the modulation of resident cells, nitric oxide and opioid pathways. 

Q2. What have the authors stated for future works in "Blockade of trpa1 with hc-030031 attenuates visceral nociception by a mechanism independent of inflammatory resident cells, nitric oxide and the opioid system" ?

229Eur J Pain 17 ( 2013 ) 223–233 © 2012 European Federation of International Association for the Study of Pain Chapters Considering the well-known participation of NO in the haemorrhagic cystitis animal model ( Souza-Filho et al., 1997 ), the authors decided to use such animal model to study the involvement of this mediator in the antinociceptive effect of HC-030031. It has been suggested that endogenous NO is involved in the inflammatory events leading to haemorrhagic cystitis after cyclophosphamide administration. Notwithstanding previous results, the authors can not rule out the modulation of TRPA1 function by inflammatory mediators. A recent published article suggests that endogenous activation of TRPA1 plays a critical role in the development of tumour necrosis factoralpha ( TNF-a ) -induced mechanical hyperalgesia ( Fernandes et al., 2011 ).