Dynamic weight bearing as a non‐reflexive method for the measurement of abdominal pain in mice

Laux-Biehlmann, Alexis; Boyken, Janina; Dahllöf, Henrik; Schmidt, Nicole; Zollner, Thomas M.; Nagel, Jens

doi:10.1002/ejp.800

Cited by 20 publications

(21 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5C,D). Furthermore, animals showed reduced pain-related spontaneous behaviours as measured in front/rear paw ratio in the dynamic weight bearing assay 38 and rearing time ( Fig. 5F), suggesting that AOC3 inhibition is leading to a reduction of oxidative stress and pain in the inoculation model.…”

Section: Inhibition Of Pro-oxidative Aoc3 Leads To Analgesic Effects mentioning

confidence: 95%

Amine oxidase 3 is a novel pro-inflammatory marker of oxidative stress in peritoneal endometriosis lesions

M-L.

Leo

Laux-Biehlmann

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Endometriosis is a common gynaecological disease of women in reproductive age, and is thought to arise from retrograde menstruation and implantation of endometrial tissue, mostly into the peritoneal cavity. The condition is characterized by a chronic, unresolved inflammatory process thereby contributing to pain as cardinal symptom in endometriosis. Elevated reactive oxygen species (ROS) and oxidative stress have been postulated as factors in endometriosis pathogenesis. We here set out for a systematic study to identify novel mechanisms and pathways relating to oxidative stress in ectopic peritoneal lesions. Using combined proteomic and transcriptomic approaches, we identified novel targets including upregulated pro-oxidative enzymes, such as amine oxidase 3/vascular adhesion protein 1 (AOC3/VAP1) as well as downregulated protective factors, in particular alkenal reductase PTGR1 and methionine sulfoxide reductase. Consistent with an altered ROS landscape, we observed hemoglobin / iron overload, ROS production and lipid peroxidation in ectopic lesions. ROS-derived 4-hydroxy-2-nonenal induced interleukin IL-8 release from monocytes. Notably, AOC3 inhibitors provoked analgesic effects in inflammatory pain models in vivo, suggesting potential translational applicability.Endometriosis, affecting 5-10% of women in reproductive age, is a gynaecological disease characterized by the presence of ectopic endometrial tissue most often found in the pelvic cavity 1,2 . Retrograde menstruation is a widely accepted pathogenic mechanism for the formation of peritoneal lesions, in which uterine epithelial and stromal cells are disseminated during menstruation and implanted into the peritoneal cavity via the Fallopian tubes 3,4 . Peritoneal lesions are macroscopically classified based on colour, appearing as white, red, brown, or black lesions. This appearance seems to be determined by endometrial gland content and a variable adjacent stromal reaction, likely reflecting a chronicity process rather than different levels of disease activity 5 . Additional contributors to disease such as genetic, epigenetic and environmental factors exist, since a majority (90%) of women undergo retrograde menstruation associated with successful clearance of menstrual debris from the peritoneal cavity 3,6-9 . However, the formation of ectopic endometrial lesions is a signature event that leads to the hallmarks of disease, comprising sustained inflammation, severe and chronic pain, as well as subfertility 10,11 . www.nature.com/scientificreports www.nature.com/scientificreports/ proteomic and transcriptomic arms of the study distinct patient populations were used and further collection details are provided in the SI material.Protein extraction and sample preparation. Tissue material was homogenised and extracted, protein extracts were subjected to in-solution trypsin digestion and data processed as described 51 . Transcriptome analysis. Illumina compatible next-generation sequencing libraries were prepared and sequenced from ribosomal RNA depleted or...

show abstract

Section: Inhibition Of Pro-oxidative Aoc3 Leads To Analgesic Effects mentioning

confidence: 95%

Amine oxidase 3 is a novel pro-inflammatory marker of oxidative stress in peritoneal endometriosis lesions

M-L.

Leo

Laux-Biehlmann

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Indeed, by week 12, rats from the ENDO group spent more time on four paws and appeared to shift their weight onto their front paws. This type of postural changes has already been described in relation to abdominal pain, as Laux-Biehlmann et al showed that mice with zymosan-induced peritonitis increase their front/rear paw ratio and decrease rearing time due to abdominal discomfort [35]. Finally, an open field assay was performed to investigate alterations in mobility or explorative behavior.…”

Section: Discussionmentioning

confidence: 82%

Mimicking Sampson’s Retrograde Menstrual Theory in Rats: A New Rat Model for Ongoing Endometriosis-Associated Pain

Persoons

Clercq

Eynde

et al. 2020

IJMS

View full text Add to dashboard Cite

Endometriosis is a prevalent gynecologic disease, defined by dysfunctional endometrium-like lesions outside of the uterine cavity. These lesions are presumably established via retrograde menstruation, i.e., endometrial tissue that flows backwards during menses into the abdomen and deposits on the organs. As ongoing pain is one of the main pain symptoms of patients, an animal model that illuminates this problem is highly anticipated. In the present study, we developed and validated a rat model for ongoing endometriosis-associated pain. First, menstrual endometrial tissue was successfully generated in donor rats, as validated by gross examination, histology and qPCR. Next, endometriosis was induced in recipient animals by intraperitoneal injection of menstrual tissue. This resulted in neuro-angiogenesis as well as established endometriosis lesions, which were similar to their human counterparts, since epithelial and stromal cells were observed. Furthermore, significant differences were noted between control and endometriosis animals concerning bodyweight and posture changes, indicating the presence of ongoing pain in animals with endometriosis. In summary, a rat model for endometriosis was established that reliably mimics the human pathophysiology of endometriosis and in which signs of ongoing pain were detected, thus providing a new research tool for therapy development.

show abstract

“…For data analysis, the raw pressure data for each of the four paws were automatically synchronized with images from the video camera and averaged values were encrypted and recorded on a computer. Using the DWB software the operator then manually “validated” each test period, ensuring that each print corresponded to the appropriate paw using the synchronized video feed as a reference (Laux‐Biehlmann et al, ; Robinson et al, ). The mean over segment of all validated values for front (left plus right) and for rear (left plus right) paws was plotted.…”

Section: Methodsmentioning

confidence: 99%

“…Using the DWB software the operator then manually "validated" each test period, ensuring that each print corresponded to the appropriate paw using the synchronized video feed as a reference (Laux-Biehlmann et al, 2016;Robinson et al, 2012). The mean over segment of all validated values for front (left plus right) and for rear (left plus right) paws was plotted.…”

Section: Dynamic Weight-bearing Testmentioning

confidence: 99%

“…The dynamic plantar aesthesiometer (DPA), an electronic von Frey instrument, is designed to record touch sensitivity on the plantar surface in rodents (Barrot, ; Piel et al, ; Tetreault et al, ; Ungard, Seidlitz, & Singh, ). The dynamic weight‐bearing (DWB) apparatus is also used to evaluate allodynia and pain in rodents by assessing the animal's spontaneous weight distribution between the four limbs while the animal moves freely (Gruen, Laux‐Biehlmann, Zollner, & Nagel, ; Laux‐Biehlmann et al, ; Lolignier et al, ; Robinson, Sargent, & Hatcher, ; Tappe‐Theodor & Kuner, ; Tetreault et al, ; Ungard et al, ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Evaluation of neurobehavioral impairment in methylmercury‐treated KK‐Ay mice by dynamic weight‐bearing test

Yamamoto

Motomura

Yanagisawa

et al. 2018

J of Applied Toxicology

View full text Add to dashboard Cite

Methylmercury (MeHg) is known to cause neurobehavioral impairment in human and experimental animals. We previously reported that MeHg (5 mg Hg/kg) induced severe neurobehavioral dysfunction in 4-week-old KK-Ay mice, although it is difficult to evaluate quantitatively the neurobehavioral impairment in MeHg-treated KK-Ay mice because of their obesity. The aim of this study was to evaluate MeHg-induced neurobehavioral dysfunction in KK-Ay mice using the dynamic weight-bearing test, which analyzes the animal's weight distribution between the four limbs. Male 12-week-old KK-Ay mice were treated with MeHg (5 mg Hg/kg) three times per week for 5 weeks. Body weight loss began after approximately 2 weeks of MeHg treatment, and decreased significantly at 4 weeks. Seven of the nine MeHg-treated mice exhibited overt neurological symptoms such as ataxia and gait disturbance. The weight-bearing load was lower for the forelimb than for the hindlimb at baseline and until 1 week after MeHg treatment was initiated. In weeks 2-4, the dynamic weight-bearing loads on the forelimb and hindlimb were similar. The load on the forelimb exceeded the load on the hindlimb after 5 weeks of treatment. This finding indicates that the dynamic weight-bearing test is useful for semi-quantitative evaluation of neurobehavioral impairment in MeHg-treated rodents, and is less stressful for the animals. Infiltration of CD204-positive macrophages was observed in the sciatic nerve of MeHg-treated mice, suggesting that CD204 can serve as a useful marker of tissue injury in peripheral nerves and a possible target in regenerating peripheral nerves and controlling neuropathies.

show abstract

Dynamic weight bearing as a non‐reflexive method for the measurement of abdominal pain in mice

Abstract: This study described for the first time the use of DWB as a non-subjective and non-reflexive method for the evaluation of inflammatory-driven abdominal pain in a mouse model.

Cited by 20 publications

References 54 publications

Amine oxidase 3 is a novel pro-inflammatory marker of oxidative stress in peritoneal endometriosis lesions

Amine oxidase 3 is a novel pro-inflammatory marker of oxidative stress in peritoneal endometriosis lesions

Mimicking Sampson’s Retrograde Menstrual Theory in Rats: A New Rat Model for Ongoing Endometriosis-Associated Pain

Evaluation of neurobehavioral impairment in methylmercury‐treated KK‐Ay mice by dynamic weight‐bearing test

Contact Info

Product

Resources

About