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1.
Exp Neurol ; 328: 113241, 2020 06.
Article in English | MEDLINE | ID: mdl-32045597

ABSTRACT

Central neuropathic pain is the main symptom caused by spinal cord lesion in relapsing-remitting multiple sclerosis (RRMS), but its management is still not effective. The transient receptor potential ankyrin 1 (TRPA1) is a pain detecting ion channel involved in neuropathic pain development. Thus, the aim of our study was to evaluate the role of TRPA1 in central neuropathic nociception induced by relapsing-remitting experimental autoimmune encephalomyelitis (RR-EAE) mouse model. In this model, we observed the development of similar clinical conditions of RRMS in C57BL/6 female mice through RR-EAE using MOG35-55 antigen and Quil A adjuvant. At the thirty-fifth day post-induction, C57BL/6 female mice demonstrated alteration in the RR-EAE score without motor impairment, mechanical and cold allodynia. Also, significative changes in demyelinating (Mog and olig-1) and neuroinflammatory (Iba1, Gfap and Tnfa) markers were observed, but this model did not alter Trpa1 RNA expression levels in the spinal cord. The hydrogen peroxide and 4-hydroxynonenal levels (TRPA1 agonists) were increased in RR-EAE induced mice, as well as the NADPH oxidase activity. The intragastric treatment of RR-EAE induced mice with TRPA1 antagonists (HC-030031 and A-967079) and antioxidant (α-lipoic acid and apocynin) caused an antiallodynic effect. Moreover, the intrathecal administration of TRPA1 antisense oligonucleotide, HC-030031, α-lipoic acid, and apocynin transiently attenuated mechanical and cold allodynia. Thus, TRPA1 plays a key role in the induction of neuropathic pain in this model of RR-EAE and can be a possible target for investigating the development of pain in RRMS patients.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental/metabolism , Hyperalgesia/metabolism , Neuralgia/metabolism , Nociception/physiology , TRPA1 Cation Channel/metabolism , Animals , Encephalomyelitis, Autoimmune, Experimental/complications , Female , Hyperalgesia/etiology , Mice , Mice, Inbred C57BL , Neuralgia/etiology
2.
Cell Mol Neurobiol ; 39(5): 605-617, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30850915

ABSTRACT

Severe and poorly treated pain often accompanies breast cancer. Thus, novel mechanisms involved in breast cancer-induced pain should be investigated. Then, it is necessary to characterize animal models that are reliable with the symptoms and progression of the disease as observed in humans. Explaining cancer-induced nociception in a murine model of breast carcinoma was the aim of this study. 4T1 (104) lineage cells were inoculated in the right fourth mammary fat pad of female BALB/c mice; after this, mechanical and cold allodynia, or mouse grimace scale (MGS) were observed for 30 days. To determine the presence of bone metastasis, we performed the metastatic clonogenic test and measure calcium serum levels. At 20 days after tumor induction, the antinociceptive effect of analgesics used to relieve pain in cancer patients (acetaminophen, naproxen, codeine or morphine) or a cannabinoid agonist (WIN 55,212-2) was tested. Mice inoculated with 4T1 cells developed mechanical and cold allodynia and increased MGS. Bone metastasis was confirmed using the clonogenic assay, and hypercalcemia was observed 20 days after cells inoculation. All analgesic drugs reduced the mechanical and cold allodynia, while the MGS was decreased only by the administration of naproxen, codeine, or morphine. Also, WIN 55,212-2 improved all nociceptive measures. This pain model could be a reliable form to observe the mechanisms of breast cancer-induced pain or to observe the efficacy of novel analgesic compounds.


Subject(s)
Mammary Neoplasms, Animal/pathology , Nociception , Acetaminophen/pharmacology , Acetaminophen/therapeutic use , Analgesics/pharmacology , Analgesics/therapeutic use , Animals , Benzoxazines/pharmacology , Benzoxazines/therapeutic use , Bone Neoplasms/blood , Bone Neoplasms/secondary , Calcium/blood , Cannabinoids/agonists , Cell Line, Tumor , Codeine/pharmacology , Codeine/therapeutic use , Disease Models, Animal , Female , Hyperalgesia/drug therapy , Hyperalgesia/etiology , Locomotion , Mammary Neoplasms, Animal/blood , Mammary Neoplasms, Animal/complications , Mammary Neoplasms, Animal/physiopathology , Mice, Inbred BALB C , Morphine/pharmacology , Morphine/therapeutic use , Morpholines/pharmacology , Morpholines/therapeutic use , Naphthalenes/pharmacology , Naphthalenes/therapeutic use , Naproxen/pharmacology , Naproxen/therapeutic use , Pain Measurement
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