FLT3 inhibitors for improving pain treatments by opioids

Abstract

Inventors have evaluated the effects of the FLT3 inhibitors on morphine analgesic potency, on tolerance to morphine analgesia and on morphine-induced mechanical pain hypersensitivity. When the FLT3 inhibitor was administered together with morphine, the amount of analgesic effect was higher than that produced by morphine alone. Repeated administration of morphine induced a progressive decrease in morphine-induced analgesia as showed by the decreased percentage of MPE in control animals. Intrathecal pre-treatment with an FLT3 inhibitor reduced the decrease in morphine analgesia. The administration of FLT3 inhibitors completely prevented both the development of morphine-induced pain hypersensitivity and morphine-revealed latent pain sensitization. Accordingly, the invention relates to an FLT3inhibitor for increasing the efficacy of an opioid for its analgesic effect, and hereby reducing the opioid dose while maintaining the opioid efficacy in a subject suffering from pain in need thereof.

Description

technical field [0001] The present invention relates to the treatment of pain. More particularly, the present invention relates to compounds and compositions for improving the efficacy of opioids and preventing and treating their side effects in subjects suffering from pain. Background technique [0002] Despite new advances in the treatment of chronic pain, opioids remain the best treatment for both acute and chronic pain. Prescribing of these drugs has also become common over the past decade, with more than 3% of adults in the US receiving long-term opioid therapy for chronic non-cancer pain (Boudreau et al., 2009). Opioids are the most effective analgesics used to treat moderate to severe pain. Morphine, buprenorphine, fentanyl, oxycodone and methadone are reference agents for patients with acute or chronic pain. In some cases, for example, in terminally ill patients, strong and repeated doses of opioid analgesics are required. However, their use is severely limited b...

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However, their use is severely limited by adverse side effects such as constipation, nausea, vomiting, sedation, and respiratory depression, and the risk of abuse, addiction, and opioid-related fatalities (Kuehn, 2009)

Most importantly, acute or chronic administration of opioids can also produce tolerance to their analgesic effects, which requires increased doses of opioids and exacerbates the side effects described above, and is known as opioid-induced hyperalgesia (OIH) pain hypersensitivity and potential pain sensitization (Rivat et al., 2002, 2007) cannot be overcome by increasing the dose of opioids and leaves patients without adequate Significantly decreased quality of life

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