Iryna A. Khasabova

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Tumors in bone are associated with pain in humans. Data generated in a murine model of bone cancer pain suggest that a disturbance of local endocannabinoid signaling contributes to the pain. When tumors formed after injection of osteolytic fibrosarcoma cells into the calcaneus bone of mice, cutaneous mechanical hyperalgesia was associated with a decrease in(More)
Inhibition of primary afferent neurons contributes to the antihyperalgesic effects of opioid and CB1 receptor agonists. Two bioassays were used to compare the effects of the CB1 receptor agonist CP 55,940 and morphine on dissociated adult rat DRG neurons. Both agonists inhibited the increase in free intracellular Ca2+ concentration evoked by depolarization;(More)
In an experimental model of cancer pain, the hyperalgesia that occurs with osteolytic tumor growth is associated with the sensitization of nociceptors. We examined functional and molecular changes in small-diameter dorsal root ganglion (DRG) neurons to determine cellular mechanisms underlying this sensitization. The occurrence of a Ca2+ transient in(More)
Metastatic and primary bone cancers are usually accompanied by severe pain that is difficult to manage. In light of the adverse side effects of opioids, manipulation of the endocannabinoid system may provide an effective alternative for the treatment of cancer pain. The present study determined that a local, peripheral increase in the endocannabinoid(More)
CB1 receptors have been localized to primary afferent neurons, but little is known about the direct effect of cannabinoids on these neurons. The depolarization-evoked increase in the concentration of free intracellular calcium ([Ca(2+)](i)), measured by microfluorimetry, was used as a bioassay for the effect of cannabinoids on isolated, adult rat primary(More)
Painful peripheral neuropathy is a dose-limiting complication of chemotherapy. Cisplatin produces a cumulative toxic effect on peripheral nerves, and 30-40% of cancer patients receiving this agent experience pain. By modeling cisplatin-induced hyperalgesia in mice with daily injections of cisplatin (1 mg/kg, i.p.) for 7 d, we investigated the(More)
Opioids do not effectively manage pain in many patients with advanced cancer. Because anandamide (AEA) activation of cannabinoid type-1 receptors (CB1R) on nociceptors reduces nociception, manipulation of AEA metabolism in the periphery may be an effective alternative or adjuvant therapy in the management of cancer pain. AEA is hydrolyzed by the(More)
The amplitude of the depolarization-evoked Ca2+ transient is larger in dorsal root ganglion (DRG) neurons from tumor-bearing mice compared with that of neurons from naive mice, and the change is mimicked by coculturing DRG neurons with the fibrosarcoma cells used to generate the tumors (Khasabova et al., 2007). The effect of palmitoylethanolamide (PEA), a(More)
Opioids are known to control the activity of P2X receptors in the sensory neurons of rats. These receptors are important in persistent pain signaling. However, there are extremely severe pain states, such as those associated with metastatic diseases, that are refractory to opioid treatment. We have tested the possibility that cancer cells affect the(More)
Painful neuropathy frequently develops as a consequence of commonly used chemotherapy agents for cancer treatment and is often a dose-limiting side effect. Currently available analgesic treatments are often ineffective on pain induced by neurotoxicity. Although peripheral administration of cannabinoids, endocannabinoids, and inhibitors of endocannabinoid(More)