Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There are some reports regarding the inhibitory effect of pain on tolerance development to analgesic effect of opioids. The present study was designed to investigate whether the chronic formalin induced pain is able to reverse analgesic tolerance to morphine and to evaluate the expression of G(alpha i/o) and G(beta) subunits of G proteins in the context of chronic pain, development of morphine tolerance and their combination. Morphine tolerance was induced by chronic systemic (intraperitoneally, i.p.) or spinal (intrathecally, i.t.) administration of morphine to male Wistar rats weighing 200-240 g and analgesia was assessed using tail flick test. Chronic pain was induced by 4 daily intraplantar injections of 50 microl of 5% formalin. Lumbar spinal tissues were assayed for the expression of G(alpha i/o) and G(beta) proteins using "semiquantitative PCR" normalized to beta-actin gene expression. Results showed that chronic formalin induced pain could reduce and reverse the development of tolerance in rats that had received chronic (i.p. or i.t.) administration of morphine. Chronic administration of morphine did not change G(alpha i/o) gene expression, while chronic pain significantly increased its expression. The expression of G(beta), however, was increased after the chronic administration of morphine, but did not change after the induction of chronic pain. None of these increases were observed when morphine and formalin were administered at the same time. Due to synchronous development of morphine tolerance and changes in expression of G(beta), it may be concluded that the development of tolerance to analgesic effect of morphine is partially mediated by increase in G(beta) gene expression. The increase in G(alpha i/o) genes expression produced by chronic pain may facilitate the opioid signaling pathway and compensate for morphine-induced tolerance.
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PMID:Changes in G proteins genes expression in rat lumbar spinal cord support the inhibitory effect of chronic pain on the development of tolerance to morphine analgesia. 1605 16

It is previously reported that the HPA axis plays role in the inhibitory effect of pain on tolerance development to analgesic effect of opioids. The present study was designed to investigate whether the chronic co-administration of dexamethasone as a glucocorticoid is also able to prevent or reverse analgesic tolerance to morphine and to compare the expression of G(alphai/o) and G(beta) subunits of G proteins in the context of chronic dexamethasone, development of morphine tolerance and their combination. Analgesic tolerance to morphine was induced by chronic intraperitoneally (i.p.) administration of morphine 20 mg/kg to male Wistar rats weighing 200-240 g within 4 consecutive days and analgesia was assessed using tail-flick test. Chronic dexamethasone was applied using 4 daily i.p. injections. Lumbar spinal tissues were assayed for the expression of G(alphai/o) and G(beta) proteins using "semiquantitative PCR" normalized to beta-actin gene expression. Results showed that chronic administration of dexamethasone could reduce and reverse the development of tolerance in rats that received chronic i.p. injections of morphine. Chronic administration of dexamethasone significantly increased the expression of G(alphai/o), while chronic administration of morphine did not change its expression. The expression of G(beta), however, was increased after the chronic administration of morphine, but did not change after the administration of chronic dexamethasone. None of these increases were observed when morphine and dexamethasone were co-administered. We conclude that the development of tolerance to analgesic effect of morphine could be prevented and reversed by dexamethasone co-administration. The increase in G(alphai/o) genes expression produced by chronic dexamethasone may facilitate the opioid signaling pathway and compensate for morphine-induced tolerance.
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PMID:Dexamethasone mimics the inhibitory effect of chronic pain on the development of tolerance to morphine analgesia and compensates for morphine induced changes in G proteins gene expression. 1682 64

There are some reports indicating that adrenalectomy significantly potentiates morphine-induced analgesia. Since G-protein subunits have an important role in morphine effects at the cellular level and the exact mechanism(s) of adrenalectomy-induced morphine sensitization has not yet been clarified, the present study was designed to determine the changes in the levels of Galphai/o, Galphas, Gbeta mRNA involved in this phenomenon. All experiments were carried out on male Wistar rats. The tail-flick test was used to assess the nociceptive threshold and corticosterone levels were measured by radioimmunoassay as a marker of HPA function. The dorsal half of the lumbar spinal cord was assayed for the expression of G-protein subunits using semiquantitative PCR normalized to beta-actin gene expression. Results showed that morphine not only in 3 mg/kg, but also in a sub-effective dose (2 mg/kg) could affect the nociceptive threshold and induce an analgesic response in adrenalectomized (ADX) rats while 2 mg/kg morphine did not demonstrate analgesic properties in sham-operated animals. These effects were reversed with corticosterone replacement. Morphine increased plasma corticosterone concentration in a dose-dependent manner in sham-operated rats. Following adrenalectomy a significant increase in the mRNA levels of Galphai/o (79%) and Gbeta (96%) was observed in the dorsal portion of the lumbar spinal cord. In contrast, no significant changes were observed in the mRNA level of Galphas. In conclusion, our results demonstrate that the levels of the cellular components involved in morphine analgesia significantly increase in ADX animals. This may be at least partly responsible for adrenalectomy-induced morphine sensitization.
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PMID:Post-adrenalectomy changes in the gene expression of specific G-protein subunits involved in morphine sensitization. 1823 77