Background: Increased prevalence of functional gastrointestinal disorders in women and perimenstrually accentuated symptoms imply that sexual hormones play a crucial role in the pathogenesis of such syndromes. The aim of this study was to analyze the selective effect of estrogen on visceral sensitivity in gonadectomized female and male Lewis rats with or without prior treatment with butyrate enemas.
Methods: Following ovariectomy (OVX) or orchiectomy (ORX) estradiol pellets (E2-P) or sham pellets (Sham-P) were implanted. After treatment with butyrate (BUT) or saline (NaCl) enemas, colorectal distensions (CRD) were performed and the visceromotor reflex (VMR) to CRD was measured by electromyography.
Key Results: Gender did not influence VMR to CRD in gonadectomized animals. VMR in E2-P animals compared to Sham-P animals was increased (635 ± 32 μVs vs 470 ± 39 μVs; p = 0.002). Overall, instillation of butyrate enemas did not influence VMR to CRD. A comparison of CRD clusters showed that butyrate enemas in the E2-P animals resulted in a significant sensitization in both OVX and ORX animals. In female rats, sensitization was also caused by estrogen substitution alone.
Conclusion & Inferences: In our animal model, estrogen is a strong factor for an increase in visceral sensory function. Surprisingly, the treatment with butyrate alone did not evoke a general rise in VMR to CRD. Rats treated with butyrate enemas and under selective estrogen substitution developed visceral sensitization during the series of CRDs.
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http://dx.doi.org/10.1111/nmo.12857 | DOI Listing |
Neurogastroenterol Motil
December 2024
Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
Background And Aims: The endocannabinoid (eCB) system includes ligands (anandamide and 2-arachidonoyl glycerol, 2-AG), receptors and catabolizing enzymes (fatty acid amide hydrolase, FAAH and monoacylglycerol lipase) expressed in both the brain and gut. We investigated whether the FAAH inhibitor, URB597, influenced visceral pain to colorectal distension (CRD) in an acute stress-related model of visceral hypersensitivity induced by the selective corticotropin-releasing factor receptor subtype 1 (CRF) agonist, cortagine.
Methods: Male Sprague-Dawley rats were injected subcutaneously (SC) with URB597 (3 mg/kg) or vehicle and 2 h later, intraperitoneally with cortagine (10 μg/kg) or vehicle.
Peptides
May 2024
Digestive Diseases Research Center and G. Oppenheimer Center for Neurobiology of Stress and Resilience, Department of Medicine, Vatche and Tamar Manoukian Division of Digestive Diseases, University of California Los Angeles, and VA Greater Los Angeles Healthcare System, CA 90073, USA.
Thyrotropin-releasing hormone (TRH) acts centrally to exert pleiotropic actions independently from its endocrine function, including antinociceptive effects against somatic pain in rodents. Whether exogenous or endogenous activation of TRH signaling in the brain modulates visceral pain is unknown. Adult male Sprague-Dawley rats received an intracerebroventricular (ICV) injection of the stable TRH analog, RX-77368 (10, 30 and 100 ng/rat) or saline (5 µl) or were semi-restrained and exposed to cold (4°C) for 45 min.
View Article and Find Full Text PDFFront Pain Res (Lausanne)
May 2023
Department of Biomedical Engineering, University of Connecticut, Storrs, CT, United States.
Introduction: Visceral motor responses (VMR) to graded colorectal distension (CRD) have been extensively implemented to assess the level of visceral pain in awake rodents, which are inevitably confounded by movement artifacts and cannot be conveniently implemented to assess invasive neuromodulation protocols for treating visceral pain. In this report, we present an optimized protocol with prolonged urethane infusion that enables robust and repeatable recordings of VMR to CRD in mice under deep anesthesia, providing a two-hour window to objectively assess the efficacy of visceral pain management strategies.
Methods: During all surgical procedures, C57BL/6 mice of both sexes (8-12 weeks, 25-35 g) were anesthetized with 2% isoflurane inhalation.
Dig Dis Sci
June 2023
Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 238 Jiefang Rd, Wuhan, 430060, Hubei, People's Republic of China.
Background: The mechanism underlying irritable bowel syndrome (IBS), a common disease with hyperalgesia, remains elusive. The spinal cholinergic system is involved in pain modulation, but its role in IBS is unknown.
Aims: To determine whether high-affinity choline transporter 1 (CHT1, a major determinant of the cholinergic signaling capacity), is implicated in spinal modulation of stress-induced hyperalgesia.
Neuron
February 2023
Department of Anesthesiology, The Center for the Study of Itch & Sensory Disorders, Washington University School of Medicine, St. Louis, MO, USA. Electronic address:
Inflammatory and functional gastrointestinal disorders such as irritable bowel syndrome (IBS) and obstructive bowel disorder (OBD) underlie the most prevalent forms of visceral pain. Although visceral pain can be generally provoked by mechanical distension/stretch, the mechanisms that underlie visceral mechanosensitivity in colon-innervating visceral afferents remain elusive. Here, we show that virally mediated ablation of colon-innervating TRPV1-expressing nociceptors markedly reduces colorectal distention (CRD)-evoked visceromotor response (VMR) in mice.
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