Alterations in Anandamide Synthesis and Degradation during Osteoarthritis Progression in an Animal Model

Bryk, Marta; Chwastek, Jakub; Kostrzewa, Magdalena; Mlost, Jakub; Pędracka, Aleksandra; Starowicz, Katarzyna

doi:10.3390/ijms21197381

Cited by 17 publications

(12 citation statements)

References 55 publications

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“…Alternations in AEA have been proven to play role during neuropathic pain development [ 113 ] and OA [ 114 ]. During OA progression, AEA synthesis and degradation enzymes were elevated in the spinal cord, synovial membrane and cartilage several days in animals after OA induction [ 114 ]. AEA and 2-AG levels were augmented in the synovial fluid of dogs with OA [ 115 ].…”

Section: Introductionmentioning

confidence: 99%

Cannabinoid-based therapy as a future for joint degeneration. Focus on the role of CB2 receptor in the arthritis progression and pain: an updated review

Bryk

Starowicz

2021

Pharmacol. Rep

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Graphic abstract Over the last several decades, the percentage of patients suffering from different forms of arthritis has increased due to the ageing population and the increasing risk of civilization diseases, e.g. obesity, which contributes to arthritis development. Osteoarthritis and rheumatoid arthritis are estimated to affect 50–60% of people over 65 years old and cause serious health and economic problems. Currently, therapeutic strategies are limited and focus mainly on pain attenuation and maintaining joint functionality. First-line therapies are nonsteroidal anti-inflammatory drugs; in more advanced stages, stronger analgesics, such as opioids, are required, and in the most severe cases, joint arthroplasty is the only option to ensure joint mobility. Cannabinoids, both endocannabinoids and synthetic cannabinoid receptor (CB) agonists, are novel therapeutic options for the treatment of arthritis-associated pain. CB 1 receptors are mainly located in the nervous system; thus, CB 1 agonists induce many side effects, which limit their therapeutic efficacy. On the other hand, CB 2 receptors are mainly located in the periphery on immune cells, and CB 2 modulators exert analgesic and anti-inflammatory effects in vitro and in vivo. In the current review, novel research on the cannabinoid-mediated analgesic effect on arthritis is presented, with particular emphasis on the role of the CB 2 receptor in arthritis-related pain and the suppression of inflammation.

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Section: Introductionmentioning

confidence: 99%

Cannabinoid-based therapy as a future for joint degeneration. Focus on the role of CB2 receptor in the arthritis progression and pain: an updated review

Bryk

Starowicz

2021

Pharmacol. Rep

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“…The synovial membrane is a more secretory tissue compared to cartilage and is responsible for synovial fluid production, joint lubrication and maintaining homeostasis of the joint (Orr et al, 2017). In turn, cartilage does not play a primary secretory role in the joint and in fact degenerates over the course of the disease, further reducing its reactivity (Bryk et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…In behavioral tests, animals were tested prior to MIA injection (day 0); to apply the 3R principle of animal testing, we determined that no healthy group was necessary. Moreover, according to the 3R principle and based on our previous behavioral research were 1 mg (Mlost et al, 2018b;Mugnaini et al, 2020;Mlost et al, 2021) or 3 mg of MIA (Malek et al, 2015;Pajak et al, 2017;Mlost et al, 2018a;Bryk et al, 2020) were successfully used, we decided to examine only 1 and 3 mg MIA doses in behavioral tests to minimize the number of animals exposed to painful procedures.…”

Section: Animalsmentioning

confidence: 99%

Sodium Monoiodoacetate Dose-Dependent Changes in Matrix Metalloproteinases and Inflammatory Components as Prognostic Factors for the Progression of Osteoarthritis

et al. 2021

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Osteoarthritis (OA) is a degenerative joint disease that primarily affects people over 65 years old. During OA progression irreversible cartilage, synovial membrane and subchondral bone degradation is observed, which results in the development of difficult-to-treat chronic pain. One of the most important factors in OA progression is joint inflammation. Both proinflammatory and anti-inflammatory factors, as well as extracellular matrix degradation enzymes (matrix metalloproteinases (MMPs), play an important role in disease development. One of the most widely used animal OA models involves an intra-articular injection of sodium monoiodoacetate (MIA) directly into the joint capsule, which results in glycolysis inhibition in chondrocytes and cartilage degeneration. This model mimics the degenerative changes observed in OA patients. However, the dose of MIA varies in the literature, ranging from 0.5 to 4.8 mg. The aim of our study was to characterize grading changes after injection of 1, 2 or 3 mg of MIA at the behavioral and molecular levels over a 28-day period. In the behavioral studies, MIA injection at all doses resulted in a gradual increase in tactile allodynia and resulted in abnormal weight bearing during free walking sequences. At several days post-OA induction, cartilage, synovial membrane and synovial fluid samples were collected, and qPCR and Western blot analyses were performed. We observed significant dose- and time-dependent changes in both gene expression and protein secretion levels. Inflammatory factors (CCL2, CXCL1, IL-1β, COMP) increased at the beginning of the experiment, indicating a transient inflammatory state connected to the MIA injection and, in more severe OA, also in the advanced stages of the disease. Overall, the results in the 1 mg MIA group were not consistently clear, indicating that the lowest tested dose may not be sufficient to induce long-lasting OA-like changes at the molecular level. In the 2 mg MIA group, significant alterations in the measured factors were observed. In the 3 mg MIA group, MMP-2, MMP-3, MMP-9, and MMP-13 levels showed very strong upregulation, which may cause overly strong reactions in animals. Therefore, a dose of 2 mg appears optimal, as it induces significant but not excessive OA-like changes in a rat model.

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“…mobilizing a subcellular reservoir near the plasma membrane that potentiate nociceptor activity (Camprubí-Robles et al, 2009). In chronic conditions, an increment in the receptor transcription and translation can also occur that contributes to prevent nociceptor desensitization upon resolution of the triggering sensitizing event (Xing et al, 2019;Bryk et al, 2020). Studies of TRPV1 function in models of neuropathic pain indicate that an increase in its function is coupled to an altered cell expression after peripheral nerve injury (Arribas-Blázquez et al, 2019;Villalba-Riquelme et al, 2022).…”

Section: Trpv1 In Painmentioning

confidence: 99%

TRPV1 in chronic pruritus and pain: Soft modulation as a therapeutic strategy

Fernández-Carvajal

Fernández‐Ballester

Ferrer‐Montiel

2022

Front. Mol. Neurosci.

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Chronic pain and pruritus are highly disabling pathologies that still lack appropriate therapeutic intervention. At cellular level the transduction and transmission of pain and pruritogenic signals are closely intertwined, negatively modulating each other. The molecular and cellular pathways involved are multifactorial and complex, including peripheral and central components. Peripherally, pain and itch are produced by subpopulations of specialized nociceptors that recognize and transduce algesic and pruritogenic signals. Although still under intense investigation, cumulative evidence is pointing to the thermosensory channel TRPV1 as a hub for a large number of pro-algesic and itchy agents. TRPV1 appears metabolically coupled to most neural receptors that recognize algesic and pruritic molecules. Thus, targeting TRPV1 function appears as a valuable and reasonable therapeutic strategy. In support of this tenet, capsaicin, a desensitizing TRPV1 agonist, has been shown to exhibit clinically relevant analgesic, anti-inflammatory, and anti-pruritic activities. However, potent TRPV1 antagonists have been questioned due to an hyperthermic secondary effect that prevented their clinical development. Thus, softer strategies directed to modulate peripheral TRPV1 function appear warranted to alleviate chronic pain and itch. In this regard, soft, deactivatable TRPV1 antagonists for topical or local application appear as an innovative approach for improving the distressing painful and itchy symptoms of patients suffering chronic pain or pruritus. Here, we review the data on these compounds and propose that this strategy could be used to target other peripheral therapeutic targets.

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Alterations in Anandamide Synthesis and Degradation during Osteoarthritis Progression in an Animal Model

Cited by 17 publications

References 55 publications

Cannabinoid-based therapy as a future for joint degeneration. Focus on the role of CB2 receptor in the arthritis progression and pain: an updated review

Cannabinoid-based therapy as a future for joint degeneration. Focus on the role of CB2 receptor in the arthritis progression and pain: an updated review

Sodium Monoiodoacetate Dose-Dependent Changes in Matrix Metalloproteinases and Inflammatory Components as Prognostic Factors for the Progression of Osteoarthritis

TRPV1 in chronic pruritus and pain: Soft modulation as a therapeutic strategy

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