Abstract
Osteoarthritis and its associated comorbidities are important clinical problems that have a negative impact on the quality of life, and its treatment remains unresolved. We investigated whether the systemic administration of slow-releasing hydrogen sulfide (H2S) donors, allyl isothiocyanate (A-ITC) and phenyl isothiocyanate (P-ITC), alleviates chronic osteoarthritis pain and the associated emotional disorders. In C57BL/6 female mice with osteoarthritis pain induced by the intra-articular injection of monosodium iodoacetate, we evaluated the effects of repeated administration of A-ITC and P-ITC on the (i) mechanical allodynia and grip strength deficits; (ii) emotional conducts; and (iii) glial activity and expression of inducible nitric oxide synthase (NOS2), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and antioxidant enzymes (heme oxygenase 1, NAD(P)H:quinone oxidoreductase-1, glutathione S-transferase mu 1 and alpha 1) in the hippocampus. The administration of A-ITC and P-ITC inhibited the mechanical allodynia, the grip strength deficits, and the depressive-like behaviors accompanying osteoarthritis. Both treatments inhibited microglial activation, normalized the upregulation of NOS2 and PI3K/p-Akt, and maintained high levels of antioxidant/detoxificant enzymes in the hippocampus. Data suggest that treatment with low doses of slow-releasing H2S donors might be an interesting strategy for the treatment of nociception, functional disability, and emotional disorders associated with osteoarthritis pain.
Highlights
Osteoarthritis is one of the most prevalent diseases affecting more than 100 million people worldwide
In other groups of animals, we investigated the effects of the intraperitoneal daily administration of 4.4 μmol/kg allyl isothiocyanate (A-ITC) or vehicle from day 25 to day 29 after monosodium iodoacetate (MIA) or SS injection and the effects of the intraperitoneal daily administration of 13.3 μmol/kg phenyl isothiocyanate (P-ITC) or vehicle from day 19 to day 29 after MIA or SS injection on the mechanical allodynia and the grip strength deficits induced by MIA (n = six animals per group)
Our results further demonstrated that the repeated administration of A-ITC and P-ITC reduced the grip strength deficits induced by MIA
Summary
Osteoarthritis is one of the most prevalent diseases affecting more than 100 million people worldwide. Osteoarthritis is a chronic degenerative joint disorder characterized by the destruction of articular cartilage causing subchondral bone alterations, inflammation, and intense pain [1]. Chronic osteoarthritis pain, which is characterized by persistent pain with inflammatory and neuropathic components, causes a physical inability to perform daily tasks, difficulty walking, etc. The treatment of chronic osteoarthritis pain remains a challenge. It is important to note that while some treatments may relieve pain, few are able to reduce the emotional disorders associated with chronic osteoarthritis pain. An investigation of new strategies that effectively relieve chronic osteoarthritis pain and the associated comorbidities, such as anxiety and depression, is essential
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