Transient receptor potential ankyrin 1 mediates headache-related cephalic allodynia in a mouse model of relapsing–remitting multiple sclerosis

Dalenogare, Diéssica Padilha; Theisen, Maria Carolina; Peres, Diulle Spat; Fialho, Maria Fernanda Pessano; Andrighetto, Nathaly; Barros, Laura Mendes; Landini, Lorenzo; Titiz, Mustafa; Logu, Francesco De; Oliveira, Sara Marchesan; Geppetti, Pierangelo; Nassini, Romina; Trevisan, Gabriela

doi:10.1097/j.pain.0000000000002520

Cited by 3 publications

(2 citation statements)

References 77 publications

(172 reference statements)

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“…In even more severe cases, there is complete hind and partial front limb paralysis, a severe condition where euthanasia is strongly recommended. Although several other behavioral domains are affected in the diverse EAE models, including the sensory domain [ 14 , 15 , 16 ] and cognition [ 17 , 18 , 19 ], or there is anxiety-like behavior [ 20 , 21 ], it is the motor behavioral deficit that serves as the primary outcome measurement in most of the EAE studies.…”

Section: Preclinical Ms Modelsmentioning

confidence: 99%

Motor Behavioral Deficits in the Cuprizone Model: Validity of the Rotarod Test Paradigm

Lubrich

Giesler

Kipp

2022

IJMS

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Multiple Sclerosis (MS) is a neuroinflammatory disorder, which is histopathologically characterized by multifocal inflammatory demyelinating lesions affecting both the central nervous system’s white and grey matter. Especially during the progressive phases of the disease, immunomodulatory treatment strategies lose their effectiveness. To develop novel progressive MS treatment options, pre-clinical animal models are indispensable. Among the various different models, the cuprizone de- and remyelination model is frequently used. While most studies determine tissue damage and repair at the histological and ultrastructural level, functional readouts are less commonly applied. Among the various overt functional deficits, gait and coordination abnormalities are commonly observed in MS patients. Motor behavior is mediated by a complex neural network that originates in the cortex and terminates in the skeletal muscles. Several methods exist to determine gait abnormalities in small rodents, including the rotarod testing paradigm. In this review article, we provide an overview of the validity and characteristics of the rotarod test in cuprizone-intoxicated mice.

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Section: Preclinical Ms Modelsmentioning

confidence: 99%

Motor Behavioral Deficits in the Cuprizone Model: Validity of the Rotarod Test Paradigm

Lubrich

Giesler

Kipp

2022

IJMS

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“…Headaches are also frequent in patients with progressive MS (PMS). Enhanced TRPA1 endogenous agonists and NADPH oxidase activity have been detected in the trigeminal ganglia of PMS-EAE and RR-EAE mice, activating TRPA1 in trigeminal nociceptors, thereby inducing periorbital mechanical hyperalgesia (Refs 64, 65). The PMS-EAE model induces depressive and anxiety-like behaviours; however, a selective TRPA1 antagonist (A-967079) reverses these behaviours, suggesting that TRPA1 plays a fundamental role in depression and anxiety-like behaviours (Ref.…”

Section: Trp and Autoimmune Diseasesmentioning

confidence: 99%

Roles of TRP and PIEZO receptors in autoimmune diseases

Yang,

Ma,

Zhu

et al. 2024

Expert Rev. Mol. Med.

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Autoimmune diseases are pathological autoimmune reactions in the body caused by various factors, which can lead to tissue damage and organ dysfunction. They can be divided into organ-specific and systemic autoimmune diseases. These diseases usually involve various body systems, including the blood, muscles, bones, joints and soft tissues. The transient receptor potential (TRP) and PIEZO receptors, which resulted in David Julius and Ardem Patapoutian winning the Nobel Prize in Physiology or Medicine in 2021, attracted people's attention. Most current studies on TRP and PIEZO receptors in autoimmune diseases have been carried out on animal model, only few clinical studies have been conducted. Therefore, this study aimed to review existing studies on TRP and PIEZO to understand the roles of these receptors in autoimmune diseases, which may help elucidate novel treatment strategies.

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Neuropathic-like Nociception and Spinal Cord Neuroinflammation Are Dependent on the TRPA1 Channel in Multiple Sclerosis Models in Mice

Dalenogare

Araújo

Landini

et al. 2023

Cells

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Background: Transient receptor potential ankyrin 1 (TRPA1) activation is implicated in neuropathic pain-like symptoms. However, whether TRPA1 is solely implicated in pain-signaling or contributes to neuroinflammation in multiple sclerosis (MS) is unknown. Here, we evaluated the TRPA1 role in neuroinflammation underlying pain-like symptoms using two different models of MS. Methods: Using a myelin antigen, Trpa1+/+ or Trpa1−/− female mice developed relapsing-remitting experimental autoimmune encephalomyelitis (RR-EAE) (Quil A as adjuvant) or progressive experimental autoimmune encephalomyelitis (PMS)-EAE (complete Freund’s adjuvant). The locomotor performance, clinical scores, mechanical/cold allodynia, and neuroinflammatory MS markers were evaluated. Results: Mechanical and cold allodynia detected in RR-EAE, or PMS-EAE Trpa1+/+ mice, were not observed in Trpa1−/− mice. The increased number of cells labeled for ionized calcium-binding adapter molecule 1 (Iba1) or glial fibrillary acidic protein (GFAP), two neuroinflammatory markers in the spinal cord observed in both RR-EAE or PMS-EAE Trpa1+/+ mice, was reduced in Trpa1−/− mice. By Olig2 marker and luxol fast blue staining, prevention of the demyelinating process in Trpa1−/− induced mice was also detected. Conclusions: Present results indicate that the proalgesic role of TRPA1 in EAE mouse models is primarily mediated by its ability to promote spinal neuroinflammation and further strengthen the channel inhibition to treat neuropathic pain in MS.

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Transient receptor potential ankyrin 1 mediates headache-related cephalic allodynia in a mouse model of relapsing–remitting multiple sclerosis

Cited by 3 publications

References 77 publications

Motor Behavioral Deficits in the Cuprizone Model: Validity of the Rotarod Test Paradigm

Motor Behavioral Deficits in the Cuprizone Model: Validity of the Rotarod Test Paradigm

Roles of TRP and PIEZO receptors in autoimmune diseases

Neuropathic-like Nociception and Spinal Cord Neuroinflammation Are Dependent on the TRPA1 Channel in Multiple Sclerosis Models in Mice

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