Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0848237 (acute stress)
 4,619 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transient receptor ion channel 1 (TRPV1) is a nociceptor involved in visceral hypersensitivity. Aminoglycosides like neomycin are not only potent antibiotics but in vitro data suggest that neomycin also acts as a TRPV1-antagonist and alleviates somatic pain responses. To what extent neomycin reduces visceral hypersensitivity remains unknown. Therefore, we aimed to investigate whether neomycin can inhibit in vivo TRPV1-dependent hypersensitivity responses in two rat models of visceral pain. In the first model rats were pretreated with intraperitoneal (i.p.) capsazepine, the selective TRPV1 antagonist SB-705498, neomycin or vehicle alone and 30 min later instilled with intracolonic TRPV1-activating capsaicin. Likewise, rats were pretreated with 10 days oral neomycin and then subjected to intracolonic capsaicin. The visceromotor response (VMR) to distension was measured before and after capsaicin application. In addition, the VMR to distension was measured in adult maternal separated rats before and after acute stress. Before the 2nd distension protocol these rats were treated with i.p. neomycin, amoxycillin or vehicle alone. Our results showed that capsaicin administration induced an enhanced VMR to distension that was prevented by i.p. capsazepine, SB-705498 and neomycin. Oral neomycin treatment changed bacterial faecal content but could not inhibit capsaicin induced visceral hypersensitivity. In maternal separated rats acute stress induced an enhanced response to distension that was reversed by i.p. neomycin, but not amoxycillin. These data indicate that (i.p.) neomycin can inhibit visceral hypersensitivity to distension in a nonbactericidal manner and suggest that TRPV1-modulation may be involved.
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PMID:Possible role for TRPV1 in neomycin-induced inhibition of visceral hypersensitivity in rat. 1929 29

Irritable bowel syndrome is in part characterized by an increased sensitivity to colonic distension. Stress is an important trigger factor for symptom generation. We hypothesized that stress induces visceral hypersensitivity via mast cell degranulation and transient receptor ion channel 1 (TRPV1) modulation. We used the rat model of neonatal maternal separation (MS) to investigate this hypothesis. The visceromotor response to colonic distention was assessed in adult MS and non-handled (NH) rats before and after acute water avoidance (WA) stress. We evaluated the effect of the mast cell stabilizer doxantrazole, neutralizing antiserum against the mast cell mediator nerve growth factor (NGF) and two different TRPV1 antagonists; capsazepine (non-specific) and SB-705498 (TRPV1-specific). Immunohistochemistry was used to assess post-WA TRPV1 expression in dorsal root ganglia and the presence of immunocytes in proximal and distal colon. Retrograde labelled and microdissected dorsal root ganglia sensory neurons were used to evaluate TRPV1 gene transcription. Results showed that acute stress induces colonic hypersensitivity in MS but not in NH rats. Hypersensitivity was prevented by prestress administration of doxantrazole and anti-NGF. Capsazepine inhibited and SB-705498 reversed poststress hypersensitivity. In MS rats, acute stress induced a slight increase in colonic mast cell numbers without further signs of inflammation. Post-WA TRPV1 transcription and expression was not higher in MS than NH rats. In conclusion, the present data on stress-induced visceral hypersensitivity confirm earlier reports on the essential role of mast cells and NGF. Moreover, the results also suggest that TRPV1 modulation (in the absence of overt inflammation) is involved in this response. Thus, mast cells and TRPV1 are potential targets to treat stress-induced visceral hypersensitivity.
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PMID:Essential role for TRPV1 in stress-induced (mast cell-dependent) colonic hypersensitivity in maternally separated rats. 1952 46

Activation of the hypothalamic-pituitary-adrenal axis (HPA) is critical for survival when the organism is exposed to a stressful stimulus. The endocannabinoid system (ECS) is currently considered an important neuromodulator involved in numerous pathophysiological processes and whose primary function is to maintain homeostasis. In the tissues constituting the HPA axis, all the components of the ECS are present and the activation of this system acts in parallel with changes in the activity of numerous neurotransmitters, including nitric oxide (NO). NO is widely distributed in the brain and adrenal glands and recent studies have shown that free radicals, and in particular NO, may play a crucial role in the regulation of stress response. Our objective was to determine the participation of the endocannabinoid and NOergic systems as probable mediators of the neuroendocrine HPA axis response to a psychophysical acute stress model in the adult male rat. Animals were pre-treated with cannabinoid receptors agonists and antagonists at central and systemic level prior to acute restraint exposure. We also performed in vitro studies incubating adrenal glands in the presence of ACTH and pharmacological compounds that modifies ECS components. Our results showed that the increase in corticosterone observed after acute restraint stress is blocked by anandamide administered at both central and peripheral level. At hypothalamic level both cannabinoid receptors (CB1 and CB2) are involved, while in the adrenal gland, anandamide has a very potent effect in suppressing ACTH-induced corticosterone release that is mainly mediated by vanilloid TRPV1 receptors. We also observed that stress significantly increased hypothalamic mRNA levels of CB1 as well as adrenal mRNA levels of TRPV1 receptor. In addition, anandamide reduced the activity of the nitric oxide synthase enzyme during stress, indicating that the anti-stress action of endocannabinoids may involve a reduction in NO production at hypothalamic and adrenal levels. In conclusion, an endogenous cannabinoid tone maintains the HPA axis in a stable basal state, which is lost with a noxious stimulus. In this case, the ECS dampens the response to stress allowing the recovery of homeostasis. Moreover, our work further contributes to in vitro evidence for a participation of the endocannabinoid system by inhibiting corticosterone release directly at the adrenal gland level.
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PMID:Pharmacological augmentation of endocannabinoid signaling reduces the neuroendocrine response to stress. 2906 62