Subject(s)
Fibromyalgia , Pain Management , Transcutaneous Electric Nerve Stimulation , Humans , Fibromyalgia/therapy , PainABSTRACT
AIMS: Melatonin has been reported to attenuate opioid tolerance. In this study, we explored the possible mechanism of melatonin in diminishing morphine tolerance. MAIN METHODS: Two intrathecal (i.t.) catheters were implanted in male Wistar rats for drug delivery. One was linked to a mini-osmotic pump for morphine or saline infusion. On the seventh day, 50µg of melatonin or vehicle was injected through the other catheter instantly after discontinuation of morphine or saline infusion; 3h later, 15µg of morphine or saline was injected. The antinociceptive response was then measured using the tail-flick test every 30min for 120min. KEY FINDINGS: The results showed that chronic morphine infusion elicited antinociceptive tolerance and upregulated heat shock protein 27 (HSP27) expression in the dorsal horn of the rat spinal cord. Melatonin pretreatment partially restored morphine's antinociceptive effect in morphine-tolerant rats and reversed morphine-induced HSP27 upregulation. In addition, chronic morphine infusion induced microglial cell activation and was reversed by melatonin treatment. SIGNIFICANCE: The present study provides evidence that melatonin, acting via inhibiting morphine-induced neuroinflammation, can be useful as a therapeutic adjuvant for patients under long-term opioid treatment for pain relief.
Subject(s)
Analgesics, Opioid/pharmacology , Drug Tolerance , HSP27 Heat-Shock Proteins/agonists , HSP27 Heat-Shock Proteins/biosynthesis , Melatonin/pharmacology , Microglia/drug effects , Morphine/pharmacology , Animals , Gene Expression Regulation/drug effects , Injections, Spinal , Macrophage Activation/drug effects , Male , Pain Measurement/drug effects , Rats , Rats, Wistar , Up-Regulation/drug effectsABSTRACT
We had previously demonstrated that excitatory amino acid glutamate plays a role in the progression and severity of knee osteoarthritis (OA), and early hyaluronic acid injection attenuates the OA progression by attenuation of knee joint glutamate level, which was also related to the cystine/glutamate antiporter system X (system XC-) expression. System XC- uptakes cystine into chondrocytes for glutathione (GSH) synthesis, but the role of system XC- in OA is rarely addressed. Sulfasalazine (SSZ) is a system XC- inhibitor; SSZ was applied intra-articularly to study the function of system XC- in the development of OA in rats subjected to anterior cruciate ligament transection and medial meniscectomy (ACLT + MMx). Moerover, the system XC- activator N-acetylcysteine (NAC) was also applied to verify the role of system XC-. The intra-articular injection of SSZ significantly attenuated knee swelling and cartilage destruction in the knees of ACLT + MMx rats and this effect was blocked by NAC. The results showed that inhibition of system XC- function can attenuate ACLT + MMx-induced cartilage destruction. In the present study, system XC- inhibitor SSZ was shown to reduce glutamate content in synovial fluid and GSH in chondrocytes. It was also showed SSZ could attenuate ACLT + MMx-induced cartilage destruction, and treatment of NAC reversed the protective effect of SSZ.
Subject(s)
Antiporters/antagonists & inhibitors , Antirheumatic Agents/therapeutic use , Knee Injuries/complications , Osteoarthritis, Knee/prevention & control , Sulfasalazine/therapeutic use , Animals , Anterior Cruciate Ligament Injuries , Antiporters/metabolism , Antirheumatic Agents/pharmacology , Cells, Cultured , Chondrocytes/drug effects , Drug Evaluation, Preclinical , Knee Injuries/metabolism , Male , Osteoarthritis, Knee/etiology , Rats, Wistar , Sulfasalazine/pharmacology , Tibial Meniscus InjuriesABSTRACT
Hedyotis diffusa Willd. (Rubiaceae) is an important folk herb used to prevent and cure hepatitis and liver cancer in Taiwan. For differentiation of H. diffusa from counterfeits, macroscopic and microscopic characters of H. diffusa, H. corymbosa and H. tenelliflora were examined in this study. According to Trypan blue exclusion assay and Western blot analysis, H. diffusa had a significant inhibition of cell growth and induction of cell apoptosis in COLO 205 (colon cancer), Hep 3B (hepatocellular carcinoma) and H460 (lung cancer) cell lines. This study also used high-performance liquid chromatography (HPLC) to determine the quality control of H. diffusa. The HPLC data showed that ursolic and oleanolic acid are the components of the H. diffusa, consisting of approximately 4.66-4.80% and 1.86-1.96%, respectively. Our study also demonstrated that ursolic acid has significant anti-tumor activity in COLO 205, Hep 3B and H460 cancer cells.