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Article ; Online: Food for thought about the immune drivers of gut pain.

Brierley, Stuart M

2021 Volume 590, Issue 7844, Page(s) 41–43

MeSH term(s)	Abdominal Pain ; Allergens ; Food ; Gastrointestinal Microbiome ; Humans ; Immunity
Chemical Substances	Allergens
Language	English
Publishing date	2021-01-11
Publishing country	England
Document type	News ; Comment
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/d41586-020-03661-y
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Article ; Online: Gut nociceptors: sentinels promoting host defense.

Brierley, Stuart M

Cell research

2020 Volume 30, Issue 4, Page(s) 279–280

MeSH term(s)	Gastrointestinal Microbiome ; Neurons ; Nociceptors ; Salmonella
Language	English
Publishing date	2020-01-28
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	1319303-x
ISSN	1748-7838 ; 1001-0602
ISSN (online)	1748-7838
ISSN	1001-0602
DOI	10.1038/s41422-020-0278-9
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Article ; Online: Peripheral and central neuroplasticity in a mouse model of endometriosis.

Castro, Joel / Maddern, Jessica / Erickson, Andelain / Harrington, Andrea M / Brierley, Stuart M

Journal of neurochemistry

2023

Abstract: Chronic pelvic pain (CPP) is the most debilitating symptom of gynaecological disorders such as endometriosis. However, it remains unclear how sensory neurons from pelvic organs affected by endometriosis, such as the female reproductive tract, detect and ... ...

Abstract	Chronic pelvic pain (CPP) is the most debilitating symptom of gynaecological disorders such as endometriosis. However, it remains unclear how sensory neurons from pelvic organs affected by endometriosis, such as the female reproductive tract, detect and transmit nociceptive events and how these signals are processed within the central nervous system (CNS). Using a previously characterized mouse model of endometriosis, we investigated whether the increased pain sensitivity occurring in endometriosis could be attributed to (i) changes in mechanosensory properties of sensory afferents innervating the reproductive tract, (ii) alterations in sensory input from reproductive organs to the spinal cord or (iii) neuroinflammation and sensitization of spinal neural circuits. Mechanosensitivity of vagina-innervating primary afferents was examined using an ex vivo single-unit extracellular recording preparation. Nociceptive signalling from the vagina to the spinal cord was quantified by phosphorylated MAP kinase ERK1/2 immunoreactivity. Immunohistochemistry was used to determine glial and neuronal circuit alterations within the spinal cord. We found that sensory afferents innervating the rostral, but not caudal portions of the mouse vagina, developed mechanical hypersensitivity in endometriosis. Nociceptive signalling from the vagina to the spinal cord was significantly enhanced in mice with endometriosis. Moreover, mice with endometriosis developed microgliosis, astrogliosis and enhanced substance P neurokinin-1 receptor immunoreactivity within the spinal cord, suggesting the development of neuroinflammation and sensitization of spinal circuitry in endometriosis. These results demonstrate endometriosis-induced neuroplasticity occurring at both peripheral and central sites of sensory afferent pathways. These findings may help to explain the altered sensitivity to pain in endometriosis and provide a novel platform for targeted pain relief treatments for this debilitating disorder.
Language	English
Publishing date	2023-05-11
Publishing country	England
Document type	Journal Article
ZDB-ID	80158-6
ISSN	1471-4159 ; 0022-3042 ; 1474-1644
ISSN (online)	1471-4159
ISSN	0022-3042 ; 1474-1644
DOI	10.1111/jnc.15843
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Article ; Online: Comparative localization of colorectal sensory afferent central projections in the mouse spinal cord dorsal horn and caudal medulla dorsal vagal complex.

Wang, QingQing / Caraballo, Sonia Garcia / Rychkov, Grigori / McGovern, Alice E / Mazzone, Stuart B / Brierley, Stuart M / Harrington, Andrea M

The Journal of comparative neurology

2023 Volume 532, Issue 2, Page(s) e25546

Abstract: The distal colon and rectum (colorectum) are innervated by spinal and vagal afferent pathways. The central circuits into which vagal and spinal afferents relay colorectal nociceptive information remain to be comparatively assessed. To address this, ... ...

Abstract	The distal colon and rectum (colorectum) are innervated by spinal and vagal afferent pathways. The central circuits into which vagal and spinal afferents relay colorectal nociceptive information remain to be comparatively assessed. To address this, regional colorectal retrograde tracing and colorectal distension (CRD)-evoked neuronal activation were used to compare the circuits within the dorsal vagal complex (DVC) and dorsal horn (thoracolumbar [TL] and lumbosacral [LS] spinal levels) into which vagal and spinal colorectal afferents project. Vagal afferent projections were observed in the nucleus tractus solitarius (NTS), area postrema (AP), and dorsal motor nucleus of the vagus (DMV), labeled from the rostral colorectum. In the NTS, projections were opposed to catecholamine and pontine parabrachial nuclei (PbN)-projecting neurons. Spinal afferent projections were labeled from rostral through to caudal aspects of the colorectum. In the dorsal horn, the number of neurons activated by CRD was linked to pressure intensity, unlike in the DVC. In the NTS, 13% ± 0.6% of CRD-activated neurons projected to the PbN. In the dorsal horn, at the TL spinal level, afferent input was associated with PbN-projecting neurons in lamina I (LI), with 63% ± 3.15% of CRD-activated neurons in LI projecting to the PbN. On the other hand, at the LS spinal level, only 18% ± 0.6% of CRD-activated neurons in LI projected to the PbN. The collective data identify differences in the central neuroanatomy that support the disparate roles of vagal and spinal afferent signaling in the facilitation and modulation of colorectal nociceptive responses.
MeSH term(s)	Mice ; Animals ; Vagus Nerve ; Afferent Pathways/physiology ; Neurons ; Spinal Cord Dorsal Horn ; Colorectal Neoplasms/metabolism ; Spinal Cord/metabolism ; Neurons, Afferent/physiology
Language	English
Publishing date	2023-10-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3086-7
ISSN	1096-9861 ; 0021-9967 ; 0092-7317
ISSN (online)	1096-9861
ISSN	0021-9967 ; 0092-7317
DOI	10.1002/cne.25546
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Article: The Regulate your Sitting Time (RESIT) intervention for reducing sitting time in individuals with type 2 diabetes: findings from a randomised-controlled feasibility trial.

Brierley, Marsha L / Chater, Angel M / Edwardson, Charlotte L / Castle, Ellen M / Hunt, Emily R / Biddle, Stuart Jh / Sisodia, Rupa / Bailey, Daniel P

Diabetology & metabolic syndrome

2024 Volume 16, Issue 1, Page(s) 87

Abstract: Background: Reducing and breaking up sitting is recommended for optimal management of Type 2 diabetes mellitus (T2DM). Yet, there is limited evidence of interventions targeting these outcomes in individuals with this condition. The primary aim of this ... ...

Abstract	Background: Reducing and breaking up sitting is recommended for optimal management of Type 2 diabetes mellitus (T2DM). Yet, there is limited evidence of interventions targeting these outcomes in individuals with this condition. The primary aim of this study was to assess the feasibility and acceptability of delivering and evaluating a tailored online intervention to reduce and break up sitting in adults with T2DM. Methods: A mixed-methods two-arm randomised controlled feasibility trial was conducted in ambulatory adults with T2DM who were randomised 1:1 to the REgulate your SItting Time (RESIT) intervention or usual care control group. The intervention included online education, self-monitoring and prompt tools (wearable devices, smartphone apps, computer apps) and health coaching. Feasibility outcomes were recruitment, attrition, data completion rates and intervention acceptability. Measurements of device-assessed sitting (intended primary outcome for definitive trial), standing and stepping, and physical function, psychosocial health and wellbeing were taken at baseline, 3 months and 6 months. Individual semi-structured interviews were conducted at six-months (post intervention) to explore acceptability, feasibility and experiences of the trial and intervention using the Framework Method. Results: Seventy participants aged 55 ± 11 years were recruited. Recruitment rate (proportion of eligible participants enrolled into the study) was 67% and participant retention rate at 6 months was 93% (n = 5 withdrawals). Data completion rates for daily sitting were 100% at baseline and ranged from 83 to 91% at 3 months and 6 months. Descriptive analysis demonstrated potential for the intervention to reduce device-measured sitting, which was 30.9 ± 87.2 and 22.2 ± 82.5 min/day lower in the intervention group at 3 and 6 months, respectively, compared with baseline. In the control group, sitting was 4.4 ± 99.5 and 23.7 ± 85.2 min/day lower at 3 and 6 months, respectively. Qualitative analysis identified three themes: reasons for participating in the trial, acceptability of study procedures, and the delivery and experience of taking part in the RESIT intervention. Overall, the measurement visits and intervention were acceptable to participants. Conclusions: This study demonstrated the feasibility and acceptability of the RESIT intervention and evaluation methods, supporting a future definitive trial. If RESIT is found to be clinically effective, this could lead to changes in diabetes healthcare with a focus on reducing sitting. Trial registration: The trial was registered with ISRCTN (number ISRCTN14832389).
Language	English
Publishing date	2024-04-24
Publishing country	England
Document type	Journal Article
ZDB-ID	2518786-7
ISSN	1758-5996
ISSN	1758-5996
DOI	10.1186/s13098-024-01336-6
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Article ; Online: The voltage-gated sodium channel Na

Castro, Joel / Maddern, Jessica / Chow, Chun Yuen / Tran, Poanna / Vetter, Irina / King, Glenn F / Brierley, Stuart M

Journal of neurochemistry

2023

Abstract: Chronic pelvic pain (CPP) is the primary symptom of endometriosis patients, but adequate treatments are lacking. Modulation of ion channels expressed by sensory nerves innervating the viscera has shown promise for the treatment of irritable bowel ... ...

Abstract	Chronic pelvic pain (CPP) is the primary symptom of endometriosis patients, but adequate treatments are lacking. Modulation of ion channels expressed by sensory nerves innervating the viscera has shown promise for the treatment of irritable bowel syndrome and overactive bladder. However, similar approaches for endometriosis-associated CPP remain underdeveloped. Here, we examined the role of the voltage-gated sodium (Na
Language	English
Publishing date	2023-02-24
Publishing country	England
Document type	Journal Article
ZDB-ID	80158-6
ISSN	1471-4159 ; 0022-3042 ; 1474-1644
ISSN (online)	1471-4159
ISSN	0022-3042 ; 1474-1644
DOI	10.1111/jnc.15795
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Article ; Online: Pruritogenic mechanisms and gut sensation: putting the "irritant" into irritable bowel syndrome.

Brizuela, Mariana / Castro, Joel / Harrington, Andrea M / Brierley, Stuart M

American journal of physiology. Gastrointestinal and liver physiology

2021 Volume 320, Issue 6, Page(s) G1131–G1141

Abstract: Chronic abdominal pain is a common clinical condition experienced by patients with irritable bowel syndrome (IBS). A general lack of suitable treatment options for the management of visceral pain is the major contributing factor to the debilitating ... ...

Abstract	Chronic abdominal pain is a common clinical condition experienced by patients with irritable bowel syndrome (IBS). A general lack of suitable treatment options for the management of visceral pain is the major contributing factor to the debilitating nature of the disease. Understanding the underlying causes of chronic visceral pain is pivotal to identifying new effective therapies for IBS. This review provides the current evidence, demonstrating that mediators and receptors that induce itch in the skin also act as "gut irritants" in the gastrointestinal tract. Activation of these receptors triggers specific changes in the neuronal excitability of sensory pathways responsible for the transmission of nociceptive information from the periphery to the central nervous system leading to visceral hypersensitivity and visceral pain. Accumulating evidence points to significant roles of irritant mediators and their receptors in visceral hypersensitivity and thus constitutes potential targets for the development of more effective therapeutic options for IBS.
MeSH term(s)	Colon/metabolism ; Histamine/metabolism ; Humans ; Hyperalgesia/metabolism ; Irritable Bowel Syndrome/metabolism ; Mast Cells/metabolism ; Visceral Pain/metabolism
Chemical Substances	Histamine (820484N8I3)
Language	English
Publishing date	2021-05-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	603840-2
ISSN	1522-1547 ; 0193-1857
ISSN (online)	1522-1547
ISSN	0193-1857
DOI	10.1152/ajpgi.00331.2020
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Article ; Online: Structure, Function, and Therapeutic Potential of the Trefoil Factor Family in the Gastrointestinal Tract.

Braga Emidio, Nayara / Brierley, Stuart M / Schroeder, Christina I / Muttenthaler, Markus

ACS pharmacology & translational science

2020 Volume 3, Issue 4, Page(s) 583–597

Abstract: Trefoil factor family peptides (TFF1, TFF2, and TFF3) are key players in protecting, maintaining, and repairing the gastrointestinal tract. Accordingly, they have the therapeutic potential to treat and prevent a variety of gastrointestinal disorders ... ...

Abstract	Trefoil factor family peptides (TFF1, TFF2, and TFF3) are key players in protecting, maintaining, and repairing the gastrointestinal tract. Accordingly, they have the therapeutic potential to treat and prevent a variety of gastrointestinal disorders associated with mucosal damage. TFF peptides share a conserved motif, including three disulfide bonds that stabilize a well-defined three-loop-structure reminiscent of a trefoil. Although multiple functions have been described for TFF peptides, their mechanisms at the molecular level remain poorly understood. This review presents the
Language	English
Publishing date	2020-06-09
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2575-9108
ISSN (online)	2575-9108
DOI	10.1021/acsptsci.0c00023
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Article ; Online: Cross-organ sensitization between the colon and bladder: to pee or not to pee?

Grundy, Luke / Brierley, Stuart M

American journal of physiology. Gastrointestinal and liver physiology

2017 Volume 314, Issue 3, Page(s) G301–G308

Abstract: Chronic abdominal and pelvic pain are common debilitating clinical conditions experienced by millions of patients around the globe. The origin of such pain commonly arises from the intestine and bladder, which share common primary roles (the collection, ... ...

Abstract	Chronic abdominal and pelvic pain are common debilitating clinical conditions experienced by millions of patients around the globe. The origin of such pain commonly arises from the intestine and bladder, which share common primary roles (the collection, storage, and expulsion of waste). These visceral organs are located in close proximity to one another and also share common innervation from spinal afferent pathways. Chronic abdominal pain, constipation, or diarrhea are primary symptoms for patients with irritable bowel syndrome or inflammatory bowel disease. Chronic pelvic pain and urinary urgency and frequency are primary symptoms experienced by patients with lower urinary tract disorders such as interstitial cystitis/painful bladder syndrome. It is becoming clear that these symptoms and clinical entities do not occur in isolation, with considerable overlap in symptom profiles across patient cohorts. Here we review recent clinical and experimental evidence documenting the existence of "cross-organ sensitization" between the colon and bladder. In such circumstances, colonic inflammation may result in profound changes to the sensory pathways innervating the bladder, resulting in severe bladder dysfunction.
MeSH term(s)	Abdominal Pain/diagnosis ; Abdominal Pain/epidemiology ; Abdominal Pain/physiopathology ; Animals ; Chronic Pain/diagnosis ; Chronic Pain/epidemiology ; Chronic Pain/physiopathology ; Colitis/diagnosis ; Colitis/epidemiology ; Colitis/physiopathology ; Colon/innervation ; Ganglia, Spinal/physiopathology ; Humans ; Nociceptors ; Pelvic Pain/diagnosis ; Pelvic Pain/epidemiology ; Pelvic Pain/physiopathology ; Prognosis ; Risk Factors ; Urinary Bladder/innervation ; Urinary Bladder Diseases/diagnosis ; Urinary Bladder Diseases/epidemiology ; Urinary Bladder Diseases/physiopathology ; Urination ; Urodynamics
Language	English
Publishing date	2017-11-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	603840-2
ISSN	1522-1547 ; 0193-1857
ISSN (online)	1522-1547
ISSN	0193-1857
DOI	10.1152/ajpgi.00272.2017
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Article: Pain in Endometriosis.

Maddern, Jessica / Grundy, Luke / Castro, Joel / Brierley, Stuart M

Frontiers in cellular neuroscience

2020 Volume 14, Page(s) 590823

Abstract: Endometriosis is a chronic and debilitating condition affecting ∼10% of women. Endometriosis is characterized by infertility and chronic pelvic pain, yet treatment options remain limited. In many respects this is related to an underlying lack of ... ...

Abstract	Endometriosis is a chronic and debilitating condition affecting ∼10% of women. Endometriosis is characterized by infertility and chronic pelvic pain, yet treatment options remain limited. In many respects this is related to an underlying lack of knowledge of the etiology and mechanisms contributing to endometriosis-induced pain. Whilst many studies focus on retrograde menstruation, and the formation and development of lesions in the pathogenesis of endometriosis, the mechanisms underlying the associated pain remain poorly described. Here we review the recent clinical and experimental evidence of the mechanisms contributing to chronic pain in endometriosis. This includes the roles of inflammation, neurogenic inflammation, neuroangiogenesis, peripheral sensitization and central sensitization. As endometriosis patients are also known to have co-morbidities such as irritable bowel syndrome and overactive bladder syndrome, we highlight how common nerve pathways innervating the colon, bladder and female reproductive tract can contribute to co-morbidity via cross-organ sensitization.
Language	English
Publishing date	2020-10-06
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2020.590823
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