Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151825 (bone pain)
 3,118 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Similar to mu opioid receptors, kappa and delta opioid receptors reside in the periphery, the dorsal root ganglion, the spinal cord, and in supraspinal regions associated with pain modulation. Both delta and kappa opioid agonists have been shown to activate pain inhibitory pathways in the central nervous system. Yet, currently there are only a few pharmacologic agents that target kappa receptors, and none that target delta receptors. Spurred by the need for an efficacious analgesic without the unwanted side effects associated with the typical clinical profile of mu opioid agonists, new research has provided insight into why the development of effective kappa and delta opioid receptor agonists has remained elusive thus far, and importantly, how these obstacles may be overcome. For example, for delta opioid agonists to be effective, a state of inflammation may be required as this induces delta opioid receptors to migrate to the surface of neuronal cells and thereby become accessible to delta opioid agonists. Studies have shown that delta opioid agonists can provide relief of inflammatory pain and malignant bone pain. Meanwhile, peripherally restricted kappa opioid agonists have been developed to target kappa opioid receptors located on visceral and somatic afferent nerves for relief of inflammatory, visceral, and neuropathic chronic pain. The recently shown efficacy of these analgesics combined with a possible lower abuse potential and side effect burden than mu opioid receptor agonists makes delta and peripherally restricted kappa opioid receptor agonists promising targets for treating pain.
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PMID:Delta and kappa opioid receptors as suitable drug targets for pain. 2002 60

Over the past few years, significant progress has been made in cancer therapy. Indeed, the lifespan of cancer patients has significantly increased. Although patients live longer, cancer-related pain remains a daily problem affecting their quality of life, especially when metastases reach the bone. In patients coping with cancer-induced bone pain, morphine and NSAIDs, often used in combination with other medications, are the most commonly used drugs to alleviate pain. However, these drugs have dose-limiting side effects. Morphine and other routinely used opioids are mu opioid receptor (MOPR) agonists. The MOPR is responsible for most opioid-related adverse effects. In the present study, we revealed potent analgesic effects of an intrathecally-administered selective delta opioid receptor (DOPR) agonist, deltorphin II, in a recently developed rat bone cancer model. Indeed, we found that deltorphin II dose-dependently reversed mechanical allodynia 14 days post-surgery in this cancer pain model, which is based on the implantation of mammary MRMT-1 cells in the femur. This effect was DOPR-mediated as it was completely blocked by naltrindole, a selective DOPR antagonist. Using the complete Freund's adjuvant model of inflammatory pain, we further demonstrated that deltorphin II was equipotent at alleviating inflammatory and cancer pain (i.e. similar ED50 values). Altogether, the present results show, for the first time, that activation of spinal DOPRs causes significant analgesia at doses sufficient to reduce inflammatory pain in a rat bone cancer pain model. Our results further suggest that DOPR represents a potential target for the development of novel analgesic therapies to be used in the treatment of cancer-related pain.
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PMID:Spinal activation of delta opioid receptors alleviates cancer-related bone pain. 2145 44