Potentiating TRPA1 by Sea Anemone Peptide Ms 9a-1 Reduces Pain and Inflammation in a Model of Osteoarthritis

Progressive articular surface degradation during arthritis causes ongoing pain and hyperalgesia that lead to the development of functional disability. TRPA1 channel significantly contributes to the activation of sensory neurons that initiate neurogenic inflammation and mediates pain signal transduct...

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Main Authors: Ekaterina E. Maleeva, Yulia A. Palikova, Viktor A. Palikov, Vitaly A. Kazakov, Maria A. Simonova, Yulia A. Logashina, Nadezhda V. Tarasova, Igor A. Dyachenko, Yaroslav A. Andreev
Format: Article
Language:English
Published: MDPI AG 2023-11-01
Series:Marine Drugs
Subjects:
Online Access:https://www.mdpi.com/1660-3397/21/12/617
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author Ekaterina E. Maleeva
Yulia A. Palikova
Viktor A. Palikov
Vitaly A. Kazakov
Maria A. Simonova
Yulia A. Logashina
Nadezhda V. Tarasova
Igor A. Dyachenko
Yaroslav A. Andreev
author_facet Ekaterina E. Maleeva
Yulia A. Palikova
Viktor A. Palikov
Vitaly A. Kazakov
Maria A. Simonova
Yulia A. Logashina
Nadezhda V. Tarasova
Igor A. Dyachenko
Yaroslav A. Andreev
author_sort Ekaterina E. Maleeva
collection DOAJ
description Progressive articular surface degradation during arthritis causes ongoing pain and hyperalgesia that lead to the development of functional disability. TRPA1 channel significantly contributes to the activation of sensory neurons that initiate neurogenic inflammation and mediates pain signal transduction to the central nervous system. Peptide Ms 9a-1 from the sea anemone <i>Metridium senile</i> is a positive allosteric modulator of TRPA1 and shows significant anti-inflammatory and analgesic activity in different models of pain. We used a model of monosodium iodoacetate (MIA)-induced osteoarthritis to evaluate the anti-inflammatory properties of Ms 9a-1 in comparison with APHC3 (a polypeptide modulator of TRPV1 channel) and non-steroidal anti-inflammatory drugs (NSAIDs) such as meloxicam and ibuprofen. Administration of Ms 9a-1 (0.1 mg/kg, subcutaneously) significantly reversed joint swelling, disability, thermal and mechanical hypersensitivity, and grip strength impairment. The effect of Ms 9a-1 was equal to or better than that of reference drugs. Post-treatment histological analysis revealed that long-term administration of Ms9a-1 could reduce inflammatory changes in joints and prevent the progression of cartilage and bone destruction at the same level as meloxicam. Peptide Ms 9a-1 showed significant analgesic and anti-inflammatory effects in the model of MIA-induced OA, and therefore positive allosteric modulators could be considered for the alleviation of OA symptoms.
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spelling doaj.art-65433f1abbfc4c76b1af2e225c2ddff22023-12-22T14:22:20ZengMDPI AGMarine Drugs1660-33972023-11-01211261710.3390/md21120617Potentiating TRPA1 by Sea Anemone Peptide Ms 9a-1 Reduces Pain and Inflammation in a Model of OsteoarthritisEkaterina E. Maleeva0Yulia A. Palikova1Viktor A. Palikov2Vitaly A. Kazakov3Maria A. Simonova4Yulia A. Logashina5Nadezhda V. Tarasova6Igor A. Dyachenko7Yaroslav A. Andreev8Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997 Moscow, RussiaBranch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Prospekt Nauki, 6, 142290 Pushchino, RussiaBranch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Prospekt Nauki, 6, 142290 Pushchino, RussiaBranch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Prospekt Nauki, 6, 142290 Pushchino, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997 Moscow, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997 Moscow, RussiaInstitute of Molecular Medicine, Sechenov First Moscow State Medical University, Trubetskaya Str. 8, Bld. 2, 119991 Moscow, RussiaBranch of the Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Prospekt Nauki, 6, 142290 Pushchino, RussiaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, 117997 Moscow, RussiaProgressive articular surface degradation during arthritis causes ongoing pain and hyperalgesia that lead to the development of functional disability. TRPA1 channel significantly contributes to the activation of sensory neurons that initiate neurogenic inflammation and mediates pain signal transduction to the central nervous system. Peptide Ms 9a-1 from the sea anemone <i>Metridium senile</i> is a positive allosteric modulator of TRPA1 and shows significant anti-inflammatory and analgesic activity in different models of pain. We used a model of monosodium iodoacetate (MIA)-induced osteoarthritis to evaluate the anti-inflammatory properties of Ms 9a-1 in comparison with APHC3 (a polypeptide modulator of TRPV1 channel) and non-steroidal anti-inflammatory drugs (NSAIDs) such as meloxicam and ibuprofen. Administration of Ms 9a-1 (0.1 mg/kg, subcutaneously) significantly reversed joint swelling, disability, thermal and mechanical hypersensitivity, and grip strength impairment. The effect of Ms 9a-1 was equal to or better than that of reference drugs. Post-treatment histological analysis revealed that long-term administration of Ms9a-1 could reduce inflammatory changes in joints and prevent the progression of cartilage and bone destruction at the same level as meloxicam. Peptide Ms 9a-1 showed significant analgesic and anti-inflammatory effects in the model of MIA-induced OA, and therefore positive allosteric modulators could be considered for the alleviation of OA symptoms.https://www.mdpi.com/1660-3397/21/12/617arthritisTRPA1TRPV1peptideMs9a-1inflammation
spellingShingle Ekaterina E. Maleeva
Yulia A. Palikova
Viktor A. Palikov
Vitaly A. Kazakov
Maria A. Simonova
Yulia A. Logashina
Nadezhda V. Tarasova
Igor A. Dyachenko
Yaroslav A. Andreev
Potentiating TRPA1 by Sea Anemone Peptide Ms 9a-1 Reduces Pain and Inflammation in a Model of Osteoarthritis
Marine Drugs
arthritis
TRPA1
TRPV1
peptide
Ms9a-1
inflammation
title Potentiating TRPA1 by Sea Anemone Peptide Ms 9a-1 Reduces Pain and Inflammation in a Model of Osteoarthritis
title_full Potentiating TRPA1 by Sea Anemone Peptide Ms 9a-1 Reduces Pain and Inflammation in a Model of Osteoarthritis
title_fullStr Potentiating TRPA1 by Sea Anemone Peptide Ms 9a-1 Reduces Pain and Inflammation in a Model of Osteoarthritis
title_full_unstemmed Potentiating TRPA1 by Sea Anemone Peptide Ms 9a-1 Reduces Pain and Inflammation in a Model of Osteoarthritis
title_short Potentiating TRPA1 by Sea Anemone Peptide Ms 9a-1 Reduces Pain and Inflammation in a Model of Osteoarthritis
title_sort potentiating trpa1 by sea anemone peptide ms 9a 1 reduces pain and inflammation in a model of osteoarthritis
topic arthritis
TRPA1
TRPV1
peptide
Ms9a-1
inflammation
url https://www.mdpi.com/1660-3397/21/12/617
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