The potential anti-inflammatory and anti-nociceptive effects of rat hemopressin (PVNFKFLSH) in experimental arthritis

Autor: Soraia K.P. Costa, Elizabeth S. Fernandes, Emer S. Ferro, Anderson Romério Azevedo Cerqueira, Marcelo Nicolas Muscará, Livia L Camargo, L. M. Yshii, André Almeida Schenka, Mayara C. F. Gewehr, Alexandre Denadai-Souza, Carla Lima, Simone A. Teixeira
Rok vydání: 2020
Předmět:
musculoskeletal diseases
0301 basic medicine
Male
medicine.medical_specialty
Knee Joint
Inflammatory arthritis
medicine.medical_treatment
Anti-Inflammatory Agents
Arthritis
Administration
Oral
Substance P
Calcitonin gene-related peptide
Injections
Intra-Articular
Nociceptive Pain
Arthritis
Rheumatoid
Rats
Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
Hemoglobins
0302 clinical medicine
Internal medicine
medicine
Leukocytes
Animals
Edema
INTERLEUCINA 6
Saline
Gait
Pharmacology
Inflammation
Behavior
Animal
business.industry
medicine.disease
Arthritis
Experimental
Hemopressin
Peptide Fragments
030104 developmental biology
Endocrinology
Nociception
chemistry
Rheumatoid arthritis
Cytokines
business
030217 neurology & neurosurgery
Receptors
Calcitonin Gene-Related Peptide
Zdroj: Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual)
Universidade de São Paulo (USP)
instacron:USP
ISSN: 1879-0712
Popis: Inflammatory arthritis, such as rheumatoid arthritis (RA), stands out as one of the main sources of pain and impairment to the quality of life. The use of hemopressin (PVNFKFLSH; Hp), an inverse agonist of type 1 cannabinoid receptor, has proven to be effective in producing analgesia in pain models, but its effect on neuro-inflammatory aspects of RA is limited. In this study, antigen-induced arthritis (AIA) was evoked by the intraarticular (i.art.) injection of methylated bovine serum albumin (mBSA) in male Sprague Dawley rats. Phosphate buffered saline (PBS)-injected ipsilateral knee joints or AIA contralateral were used as control. Nociceptive and inflammatory parameters such as knee joint oedema and leukocyte influx and histopathological changes were carried out in addition to the local measurement of interleukins (IL) IL-6, IL-1β, tumor necrosis factor-α and the immunoreactivity of the neuropeptides substance P (SP) and calcitonin gene related peptide (CGRP) in the spinal cord (lumbar L3-5 segments) of AIA rats. For 4 days, AIA rats were treated daily with a single administration of saline, Hp injected (10 or 20 μg/day, i.art.), Hp given orally (20 μg/Kg, p.o.) or indomethacin (Indo; 5 mg/Kg, i.p.). In comparison to the PBS control group, the induction of AIA produced a significant and progressive mono-arthritis condition. The degree of AIA severity progressively compromised the normal walking pattern and impaired mobility over the next four days in relation to PBS-injected rats or contralateral knee joints. In AIA rats, the reduction of the distance between footprints and disturbances of gait evidenced signs of nociception. This response worsened at day 4, and a loss of footprint from the ipsilateral hind paw was evident. Daily treatment of the animals with Hp either i.art. (10 and 20 μg/knee) or p.o. (20 μg/Kg) as well as Indo (5 mg/Kg, i.p.) ameliorated the impaired mobility in a time-dependent manner (P 0.05). In parallel, the AIA-injected ipsilateral knee joints reach a peak of swelling 24 h after AIA induction, which persisted over the next four days in relation to PBS-injected rats or contralateral knee joints. There was a significant but not dose-dependent inhibitory effect produced by all dosages and routes of Hp treatments on AIA-induced knee joint swelling (P 0.05). In addition, the increased synovial levels of MPO activity, total leukocytes number and IL-6, but not IL-1β, were significantly reduced by the lower i.art. dose of Hp. In conclusion, these results successfully demonstrate that Hp may represent a novel therapeutic strategy to treat RA, an effect which is unrelated to the proinflammatory actions of the neuropeptides CGRP and SP.
Databáze: OpenAIRE
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