A5090440920- Gastrointestinal motility and disorders
- Pain Mechanisms and Treatments
- Neuropeptides and Animal Physiology
- Cannabis and Cannabinoid Research
- Pharmacological Receptor Mechanisms and Effects
- Anesthesia and Pain Management
- Diet and metabolism studies
- Pediatric Pain Management Techniques
- Pain Management and Opioid Use
- Gut microbiota and health
- Botulinum Toxin and Related Neurological Disorders
- Pharmacology and Obesity Treatment
- Neuroscience and Neuropharmacology Research
- Biochemical effects in animals
- Asthma and respiratory diseases
- Complementary and Alternative Medicine Studies
- Gastrointestinal disorders and treatments
- Music Therapy and Health
- Clostridium difficile and Clostridium perfringens research
- Cancer, Stress, Anesthesia, and Immune Response
- Opioid Use Disorder Treatment
- Ion Channels and Receptors
- Stress Responses and Cortisol
- Nausea and vomiting management
- Herbal Medicine Research Studies
Queen's University
2020-2025
Kingston General Hospital
2021-2025
Queens University
2021
The effectiveness of µ-opioid receptor (MOPr) agonists for treatment visceral pain is compromised by constipation, respiratory depression, sedation and addiction. We investigated whether a fentanyl analogue, (±)-N-(3-fluoro-1-phenethylpiperidine-4-yl)-N-phenyl propionamide (NFEPP), which preferentially activates MOPr in acidified diseased tissues, would inhibit preclinical model inflammatory bowel disease (IBD) without side effects healthy tissues.Antinociceptive actions NFEPP were compared...
We recently showed that a bacterial infection can break oral tolerance to food and lead IgE-dependent mast cell activation food-induced abdominal pain, which could constitute an important pathogenic mechanism in post-infectious irritable bowel syndrome (IBS). Here, we investigated whether similar immune mechanisms response psychological stress food-evoked pain signaling, thus potentially explain the pathophysiology larger group of patients with IBS. Mice were exposed ovalbumin (OVA) during...
While effective in treating abdominal pain, opioids have significant side effects. Recent legalization of cannabis will likely promote use cannabinoids as an adjunct or alternative to opioids, despite a lack evidence. We aimed investigate whether inhibit mouse colonic nociception, alone combination with at low doses. Experiments were performed on C57BL/6 male and female mice. Visceral nociception was evaluated by measuring visceromotor responses (VMR), afferent nerve mechanosensitivity...
Objective Dietary therapies for irritable bowel syndrome (IBS) have received increasing interest but predicting which patients will benefit remains a challenge due to lack of mechanistic insight. We recently found evidence role the microbiota in dietary modulation pain signalling humanised mouse model IBS. This randomised cross-over study aimed test hypothesis that relief following reduced consumption fermentable carbohydrates is result changes luminal neuroactive metabolites. Design IBS...
Abstract Background Monosodium glutamate (MSG) has been identified as a trigger of abdominal pain in irritable bowel syndrome (IBS), but the mechanism is unknown. This study examined whether MSG causes visceral hypersensitivity using water‐avoidance stress (WAS) mouse model pain. Methods Mice were divided into four groups receiving treatment for 6 days: WAS + gavage, saline sham‐WAS and gavage. The acute effects intraluminal administration 10 μM on jejunal extrinsic afferent nerve...
Targeting the acidified inflammatory microenvironment with pH-sensitive opioids is a novel approach for managing visceral pain while mitigating side effects. The analgesic efficacy of pH-dependent has not been studied during evolution inflammation, where fluctuating tissue pH and repeated therapeutic dosing could influence analgesia Whether can inhibit human nociceptors extracellular acidification unexplored. We side-effect profile fentanyl analog, (±)- N...
Abstract Background and Purpose Tolerance to the analgesic effects of opioids resultant dose escalation is associated with worsening side greater addiction risk. Here, we compare development tolerance conventional opioid fentanyl a novel pH‐sensitive μ ‐opioid receptor (MOR) agonist, (±)‐N‐(3‐fluoro‐1‐phenethylpiperidine‐4‐yl)‐N‐phenyl propionamide (NFEPP) that active only in acidic inflammatory microenvironments. Experimental Approach An model was developed male C57BL/6 mice, without...
Abstract Background Abdominal pain is a debilitating symptom in patients with inflammatory bowel disease. Previously we have shown that combining sub-analgesic doses of cannabinoid 1 receptor (CB1R), but not 2 (CB2R), and mu-opioid (MOR) agonists synergistically inhibits colonic nociception healthy mice. However, it unknown whether this combination has analgesic efficacy pre-clinical model colitis. Aims To determine the effects CBR MOR on during acute Methods Colitis was induced male female...
Abdominal pain is a major symptom of diseases that are associated with microbial dysbiosis, including irritable bowel syndrome and inflammatory disease.Germ-free mice more prone to abdominal than conventionally-housed mice, reconstitution the microbiota in germ-free reduces sensitivity.However, mechanisms underlying modulation remain elusive.We hypothesized disruption intestinal modulates excitability peripheral nociceptive neurons.In vivo vitro assays visceral sensation were performed on...
Abstract Background With the recent legalization of recreational marijuana in Canada, increasing numbers patients with gastrointestinal (GI) disorders are using cannabis to treat their pain, either alone or together opioids. However, little is known about potential benefits cannabinoids for treating visceral pain originating within GI tract and whether combined use opioids could enable reduction even discontinuation Aims To investigate effects combination on colonic nociceptive nerves....
Abstract Background Opioids provide effective pain relief during flares of inflammatory bowel disease but are limited by serious side effects. We showed that acute administration a novel pH-sensitive opioid agonist, NFEPP, had potent analgesic effects in inflamed acidified colonic tissues without typical However, the repeated application NFEPP course an flare inflammation unknown. Aims To assess and effect profile resulting from applications colitis. Methods Acute colitis C57BL/6 mice was...
Abstract Background Opioid drugs are used to treat pain in inflammatory bowel disease (IBD) but their side effects can cause serious morbidity. Therefore, we tested a novel opioid analgesic, ±)-N-(3-fluoro-1-phenethylpiperidine-4-yl)-N-phenylpropionamide (NFEPP) which selectively activates peripheral µ-opioid receptors at acidic pH, as occurs inflamed tissue. Aims Evaluate whether NFEPP causes analgesia the colon of DSS-colitis mice using both vitro and vivo techniques. Methods To measure...
Abstract Background Abdominal pain can be triggered by food ingestion in IBS patients. Previously we have shown that a antigen induces local release of immune mediators the colon increase dorsal root ganglion (DRG) neuron excitability when there is previous exposure presence psychological stress. However, it unknown if this effect limited to colon. Furthermore, involvement histamine neuronal hyperexcitability suggests stress-food interaction evokes Th2 response. Thus, sought investigate role...
Abstract Background Food and stress are common triggers of symptoms in IBS patients. We previously showed a murine model that exposure to food antigen during period psychological leads visceral hypersensitivity both the ileum colon upon re-exposure antigen. This was inhibited by blocking mast cells histamine receptors, suggesting cell activation is involved this increased pain signaling. However, it unknown if immunoglobulin E (IgE) leading hypersensitivity. Purpose Determine role IgE...
Abstract Background Adequate pain control in inflammatory bowel disease (IBD) can require opioids due to their high analgesic potency. The long-term use of opioids, however, is limited by the development tolerance. This leads reduced efficacy over time, resulting escalating opioid dosing and thus increased risk serious side effects. We previously demonstrated safety effectiveness a novel pH-sensitive µ-opioid receptor (MOR) agonist, NFEPP, murine colitis model, but its tolerance potential...
Abstract Background Abdominal pain is a debilitating symptom in patients with inflammatory bowel disease. Previously we have shown that both cannabinoid-1 receptor (CB1R) and mu opioid (MOR) agonists inhibit mechanosensitivity of colonic nociceptive nerves healthy mice. However, it unknown whether CBR MOR continue to effects during colitis. Purpose To determine the on acute Method Colitis was induced male female C57BL/6 mice using 2.5% dextran sodium sulfate drinking water. Visceromotor...
Abstract Background Previously we have shown that both cannabinoid 1 receptor (CB1R) and mu-opioid (MOR) agonists inhibit mechanosensitivity of colonic nociceptive nerves. However, it is unknown whether opioid receptors a synergistic interaction, such very low doses these can be employed to reduce visceral pain side effects. Aims To determine the effects combined on its Methods Telemetric transmitters were surgically implanted into abdominal cavity C57/BL6 mice, with electrodes sutured...
Abdominal pain is a major symptom of diseases associated with microbial dysbiosis. Disruption the gut microbiota antibiotics increases visceral pain, and germ-free mice are more prone to than conventionally-raised mice. However, mechanisms underlying modulation remain elusive. We hypothesized that disruption intestinal modulates excitability peripheral nociceptive neurons. Patch clamp electrophysiological recordings dorsal root ganglion (DRG) neuron were obtained from control treated...