naloxone and Osteoarthritis--Knee

Exercise is commonly recommended for patients with osteoarthritis (OA) pain. However, whether exercise is beneficial in ameliorating ongoing pain that is persistent, resistant to nonsteroidal antiinflammatory drugs (NSAIDs), and associated with advanced OA is unknown.. Rats treated with intraarticular (IA) monosodium iodoacetate (MIA) or saline underwent treadmill exercise or remained sedentary starting 10 days postinjection. Tactile sensory thresholds and weight bearing were assessed, followed by radiography at weekly intervals. After 4 weeks of exercise, ongoing pain was assessed using conditioned place preference (CPP) to IA or rostral ventromedial medulla (RVM)-administered lidocaine. The possible role of endogenous opioids in exercise-induced pain relief was examined by systemic administration of naloxone. Knee joints were collected for micro-computed tomography (micro-CT) analysis to examine pathologic changes to subchondral bone and metaphysis of the tibia.. Treadmill exercise for 4 weeks reversed MIA-induced tactile hypersensitivity and weight asymmetry. Both IA and RVM lidocaine D35, administered post-MIA, induced CPP in sedentary but not exercised MIA-treated rats, indicating that exercise blocks MIA-induced ongoing pain. Naloxone reestablished weight asymmetry in MIA-treated rats undergoing exercise and induced conditioned place aversion, indicating that exercise-induced pain relief is dependent on endogenous opioids. Exercise did not alter radiographic evidence of OA. However, micro-CT analysis indicated that exercise did not block lateral subchondral bone loss or trabecular bone loss in the metaphysis, but did block MIA-induced medial bone loss.. These findings support the conclusion that exercise induces pain relief in advanced, NSAID-resistant OA, likely through increased endogenous opioid signaling. In addition, treadmill exercise blocked MIA-induced bone loss in this model, indicating a potential bone-stabilizing effect of exercise on the OA joint.

Topics: Anesthetics, Local; Animals; Arthralgia; Arthritis, Experimental; Behavior, Animal; Disease Models, Animal; Enzyme Inhibitors; Hyperalgesia; Injections, Intra-Articular; Iodoacetic Acid; Knee Joint; Lidocaine; Male; Medulla Oblongata; Naloxone; Narcotic Antagonists; Osteoarthritis, Knee; Physical Conditioning, Animal; Rats; Rats, Sprague-Dawley; Tibia; Weight-Bearing; X-Ray Microtomography

Topics: Aged, 80 and over; Analgesics, Opioid; Drug Combinations; Fentanyl; Humans; Male; Naloxone; Nocturnal Myoclonus Syndrome; Osteoarthritis, Knee; Restless Legs Syndrome; Self Medication; Substance Withdrawal Syndrome; Tilidine

Over the past twenty years, neuroscience has changed our understanding of placebo analgesia. Often perceived by researchers as a response bias adding noise to the assessment of efficacy, in the patients' view, it is associated with charlatanism. The origin of the word, qualifying a patient's response to "please" the doctor, did not help its rightful appreciation. However, today the placebo analgesia is considered as a psychobiological phenomenon. Thanks to pharmacological manipulations and the development of functional brain imaging, the neural circuitry involved in this effect as well as the role of endorphins and dopamine have been identified. This article describes our current knowledge about this fascinating phenomenon: a psychological modulation can lead to a biological effect.

Topics: Aged; Analgesia; Chronic Disease; Dopamine; Endorphins; Female; Humans; Naloxone; Narcotic Antagonists; Neurosciences; Osteoarthritis, Knee; Pain; Placebo Effect; Placebos; Prefrontal Cortex; Treatment Outcome

Topics: Analgesia; Female; Humans; Naloxone; Narcotic Antagonists; Neurosciences; Osteoarthritis, Knee; Pain; Placebo Effect; Placebos; Prefrontal Cortex