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 a few reports in the literature that cytokines can induce analgesia (5, 6, 18). The present study sought to characterize the analgesic effects of intracerebroventricularly (icv) administered interleukin-1 (IL-1) and interferon-alpha (IFN-alpha) in rats. In the cold-water tail-flick test (CWT), latency to tail withdrawal from a -3 degrees C liquid was timed; in the hot-plate test (HP), latency to a rear paw lick or a jump from a 55 degrees C surface was measured. In some experiments, core body temperature was also monitored with a rectal thermistor. In the CWT, human recombinant (hr) IFN-alpha induced a small, statistically significant effect at just one dose (15,000 U icv), but no dose of hr-IL-1 alpha (250-1000 U icv) or hr-IL-1 beta (125-2000 U icv) induced a significant effect at any time point. On the other hand, dose-related increases in body temperature were observed after icv injection of both IL-1 alpha and IL-1 beta. The largest hyperthermic effect was a 1.7 (+/- 0.15) degrees C rise 120 min after administration of 1000 U IL-1 beta. In a second analgesic assay, the HP, IL-1 beta was ineffective as well. Since IL-1 alone did not induce analgesia, we tested its capacity to potentiate morphine analgesia. Morphine (5.0 and 10 micrograms, icv) induced analgesia in the CWT (32.7 and 61.8% maximum analgesia, respectively); however, there was no significant effect of IL-1 beta on morphine-induced analgesia. In summary, we failed to find an analgesic effect of IL-1, alone or in combination with morphine, at doses which clearly had a physiological effect; this is in contrast to the reports cited above.
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PMID:Pyrogenic doses of intracerebroventricular interleukin-1 did not induce analgesia in the rat hot-plate or cold-water tail-flick tests. 823 28

Forty-one ovarian cancer patients with less than 2 cm residual disease after systemic cisplatin-based chemotherapy received 4 courses of an ip regimen including cisplatin (75 mg/m2), mitoxantrone (20 mg/m2), and interferon-alpha 2b (30 mil IU/m2). The most important side effects were abdominal pain and fatigue. Overall 15/41 patients (37%) required narcotic analgesia for severe abdominal pain. In 1 case laparotomy was necessary due to bowel obstruction. Grade 3-4 myelotoxicity was observed in 18/41 patients (28 courses). No treatment-related death occurred. Pathological complete response (pCR) was achieved in 23/37 (62%) evaluable patients. Four-year disease-free survival was 50%, and no relapse occurred after 32 months. The estimated 4-year progression-free survival (PFS) and overall survival were 35 and 60%, respectively. Patients who achieved pCR showed significantly better survival than the others (P < 0.000). At multivariate Cox's analysis pCR achievement was the most important predictor of PFS (P < 0.005) and survival (P < 0.02). Age (< or = 60 vs > 60) and CA-125 serum levels at entry (normal vs increased) also showed independent predictive value. On the basis of multivariate analysis results we created a risk model for survival and PFS based on age and CA-125 at entry. We identified three subgroups of patients with significantly different outcomes. With this new ip combination long-term disease-free survival is achieved in a significant part of ovarian cancer patients with small tumor burden. A longer follow-up is needed to see whether it can cure some of these patients, and further comparisons with other ip or systemic regimens are needed to draw definitive conclusions about its role in these patients.
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PMID:Intraperitoneal (ip) cisplatin-mitoxantrone-interferon-alpha 2b in ovarian cancer patients with minimal residual disease. 834 66

Recent studies have revealed that the brain produces interferon-alpha (IFN-alpha) in response to noninflammatory as well as inflammatory stress and that it might have a role in normal physiology. When administered intracerebrally, IFN-alpha causes diverse effects including fever, anorexia, analgesia and changes in the central neuronal activities. These responses are inhibited by the opioid receptor antagonist naloxone. This is consistent with the reports suggesting that recombinant human (rh) IFN-alpha binds to opioid receptors in rodent brain membrane. We revealed that rhIFN-alpha altered the activity of thermosensitive neurons in the medial preoptic area (MPO) and glucose-responsive neurons in the ventromedial hypothalamus in an opioid-receptor-dependent way. As a stress which produces opioid-dependent analgesia is known to suppress the cytotoxicity of splenic natural killer cells, we investigated whether the administration of beta-endorphin and rhIFN-alpha may induce a similar immunosuppression. We found that central, but not peripheral, injection of both compounds inhibited natural killer (NK) cytotoxicity. Further studies revealed that rhIFN-alpha decreased the activity of MPO neurons via opioid receptors and the altered activity of MPO neurons in turn resulted in the activation of corticotropin-releasing factor neurons, thereby suppressing NK cytotoxicity predominantly through activation of the splenic sympathetic nerve and beta-receptor mechanisms in splenocytes. Thus, IFN-alpha may alter the brain activity to exert a feedback effect on the immune system. Further detailed whole-cell clamping analyses on neuronal mechanisms in rat brain tissue slices showed that the inhibitory effect of rhIFN-alpha on N-methyl-D-aspartate-induced membrane current responses of MPO neurons was mediated not only by opioid receptors but also by the local production of reactive oxygen intermediates, nitric oxide and prostanoids, possibly due to neuron-glial cell interaction.
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PMID:Neuroimmunomodulatory actions of hypothalamic interferon-alpha. 973 Jun 83