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)

The medical methods of terminating early pregnancy, i.e., prostaglandins, progesterone synthesis inhibitors and progesterone receptor antagonists are reviewed and compared to vacuum aspiration from the research literature. All of these methods have decreasing effectiveness up to the 9th week, when rates of incomplete abortions increase to about 40%. 1 PGF analogue and 3 PGE analogues are available and feasible for clinical use as early abortifacients. Gastrointestinal side effects are universal with the PGF, but only 20-40% with the PGE analogues. Epostane is a progesterone synthesis inhibitor, blocking 3beta-OH-steroid dehydrogenase. RU-486 and ZK 98734 are progesterone receptor antagonists. These drugs cause progesterone withdrawal over a few days, causing detachment of the trophoblast, impaired beta-hCG production, increased sensitivity of the myometrium to PGs and possibly ripening of the cervix. A single 800 mg dose of RU-486 induced complete abortion in 85% of women up to 10 days after the missed period. For routine clinical use RU-486 is taken for 3 days and sulprostone or gemeprost (PG analogs) are given intramuscularly or vaginally, with results comparable to vacuum aspiration. Bleeding lasts longer with the combined medical treatment, averages 62-81 ml, but may be severe enough to require transfusion in 0.15%. About 40% of women had nausea and vomiting. Progesterone and hCG levels declined rapidly after 3 days, and prolactin levels rose. With PGs, cortisol levels rise and the pregnancy hormones fall more rapidly. The antiprogestins decrease glucocorticoid activity but not enough to affect the feedback system. While no psychological studies have been reported comparing the combined medical abortion treatment with vacuum aspiration, prostaglandin treatment was preferred over aspiration. Home treatment with PGs, however, reduced proportion of women needing morphine analgesia from 40 to 5% compared to hospitalization.
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PMID:Medical methods to terminate early pregnancy. 222 1

Ethanol is well known to enhance the potencies of a range of anesthetics. However, its effects on steroid anesthesia have not been reported. Because ethanol often is added to the delivery vehicle to increase steroid solubility, it is important to evaluate its contribution to steroid anesthesia. Intravenous injection of ethanol and anesthetic steroid(s) produced marked analgesia and a marked increase in the number of mice exhibiting the loss of righting response (LRR). Ethanol alone at these low doses was merely sedative, and steroid alone was hypnotic without any analgesic benefit. The nocifensive response to tail clamp was used as a measure of analgesia. Progesterone or the anesthetic steroid, 3 alpha-hydroxy-5 alpha- pregnan-20-one (3 alpha) alone reduced, but did not abolish the nocifensive response. Progesterone (80 mg/kg) or 3 alpha (3 mg/kg) administered together with ethanol (1.1 g/kg) abolished the nocifensive response (analgesia) and resulted in LRR within 10 s. The onset of both effects was rapid, and the duration was greater than 8 min. With 3 alpha alone, the reduced nocifensive behavior fully returned before the mouse regained the righting response. Thus, the evaluation of the nocifensive response is not precluded by LRR. The rapid onset of LRR and analgesia suggest that 3 alpha and progesterone, not their metabolites, are responsible for the observed activities.
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PMID:Analgesia with anesthetic steroids and ethanol. 831 42

To assess the possible relationship between an increase in progesterone concentration in cerebrospinal fluid (CSF) and enhancement of spread of spinal anaesthesia, we have measured CSF progesterone concentrations in 134 patients undergoing spinal anaesthesia with hyperbaric amethocaine 8 mg. Patients were allocated to one of five groups according to the gestational period: non-pregnant group (n = 13), first trimester group (8-12 weeks, n = 16), second trimester group (13-24 weeks, n = 18), third trimester group (25-36 weeks, n = 38) and term group (37-41 weeks, n = 49). Progesterone concentration in CSF was higher in the third trimester and term groups than in the non-pregnant, first trimester and second trimester groups. Maximum cephalad spread of analgesia was higher in the second trimester, third trimester and term groups than in the non-pregnant and first trimester groups. Although an increase in CSF progesterone concentration in the second trimester group was similar in magnitude to that observed in the first trimester group, enhanced spread of spinal anaesthesia, comparable in magnitude with that observed in the term group, occurred in the second trimester group. There was no significant correlation between CSF progesterone concentration and spread of spinal anaesthesia in any of the groups. These data suggest that not only a minimum level of progesterone in CSF but also a certain duration of exposure to elevated CSF progesterone concentrations may be necessary for enhancement of spread of spinal anaesthesia, and that values of CSF progesterone concentration do not correlate directly with enhancement of spread of spinal anaesthesia.
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PMID:Cerebrospinal fluid progesterone in pregnant women. 888 43

The efficacy of 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-Androstanediol; 3 alpha-Diol) and 4-pregnen-3,20-dione (progesterone; P) in promoting analgesia was investigated. Ovariectomized rats received daily injections of 3 alpha-Diol (0.6, 3.0, 6.0 and 7.5 mg/kg) or vehicle and twice daily injections of estradiol-17 beta (E2: 1 microgram) for 2 days. Progesterone (0.5, 1.0, 2.0 and 4.0 mg/kg) or its vehicle was given on the third day and nociceptive testing using the radiant heat tailflick method was carried out 4 h later. In Expt. 1, P and 3 alpha-Diol both produced analgesia and had biphasic dose-response effects when administered singly. 3 alpha-Diol (3.0 mg/kg) elevated tailflick latencies in E2-primed animals above those following vehicle, 6.0 or 7.5 mg/kg 3 alpha-Diol; 6.0 and 7.5 mg/kg produced elevations that were greater than vehicle but less than 3.0 mg/kg. Progesterone (0.5 and 1.0 mg/kg) also elevated tailflick latencies above vehicle controls, while 2.0 and 4.0 mg/kg produced intermediate effects. In Expt. 2, 3 alpha-Diol (3 alpha-Diol:BSA) and P (P:BSA) conjugated to bovine serum albumin (BSA) were applied to the medial basal hypothalamus (MBH) and preoptic area (POA) to ascertain whether the steroids' analgesic actions were mediated by membrane actions in these sites. Free P and P:BSA both increased tailflick latencies when applied to the MBH, while 3 alpha-Diol and 3 alpha-Diol:BSA elevated latencies when applied to the POA, suggesting the steroids' effects occur in part at the neuronal membrane. In Expt. 3, free P or P:BSA applied to the MBH did not increase tailflick latencies if systemic P was given concurrently. Similarly, free 3 alpha-Diol and 3 alpha-Diol:BSA implants into the POA failed to increase tailflick latencies if s.c. 3 alpha-Diol was co-administered. These data indicate that P and 3 alpha-Diol at moderate doses have analgesic effects in part via membrane actions within the MBH and POA, respectively.
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PMID:Analgesic effects of the neurosteroid 3 alpha-androstanediol. 886 50

Intracerebral microdialysis was used to measure changes in the extracellular level of substance P (SP) released from the periaqueductal gray (PAG) and the preoptic anterior hypothalamus (POAH) of freely moving Sprague-Dawley rats after noxious cold stimulation. Artificial cerebrospinal fluid was perfused into the dialysis probe in the PAG or POAH and samples were collected every 30 min for 4 hr. SP-like immunoreactivity in the samples was measured by radioimmunoassay. In the PAG, SP base-line release was 0.43 +/- 0.08 fmol/fraction. SP release was increased to 1.3 +/- 0.4 fmol/fraction during the first collection period after noxious cold. Pretreatment with the selective mu opioid receptor agonist PL017 (0.8-3.4 nmol) or the kappa opioid receptor agonist dynorphin A1-17 (4.6-9.2 nmol), administered into the PAG by microinjection, produced dose-related inhibition of the cold-evoked SP release. Naloxone (10 mg/kg s.c.) administration 10 min before these opioid agonists reduced the inhibition of SP release. In the POAH, SP base-line release was 0.45 +/- 0.06 fmol/fraction and noxious cold did not cause any significant change in SP release. Microdialysis of SP (271 fmol-271 pmol/microl/min, for 30 min) into the PAG, but not the POAH, induced dose-related analgesia (35-68% MPA) in the cold-water tail-flick test. However, microdialysis of SP into the POAH or PAG failed to induce any significant change in body temperature. These data suggest that 1) SP released from the PAG acts as a neuromodulator to transmit nociceptive information; 2) opioid receptor agonists can suppress this information by inhibiting SP release; 3) SP evoked by noxious cold may have a role in triggering the antinociceptive function of the PAG; and 4) SP does not appear to act as a neuromodulator for thermoregulatory responses in the POAH.
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PMID:Substance P release in the rat periaqueductal gray and preoptic anterior hypothalamus after noxious cold stimulation: effect of selective mu and kappa opioid agonists. 926 75

There is a qualitative sex difference in the neurochemical mediation of stress-induced and kappa-opioid analgesia; these phenomena are dependent on N-methyl-d-aspartic acid (NMDA) receptors in males but not females. Progesterone modulation of this sex difference was examined in mice. Analgesia against thermal nociception was produced by forced cold water swim or by systemic administration of the kappa-opioid agonist, U50,488. As seen previously, the NMDA receptor antagonist MK-801 blocked both forms of analgesia in male but not female mice. Also as in previous studies, this sex difference was found to be dependent on ovarian hormones such that ovariectomy induced female mice to "switch" to the male-like, NMDAergic system. We now demonstrate that a single injection of progesterone (50 microg), systemically administered 30 min before analgesia assessment, is sufficient to restore female-specific mediation of analgesia (i.e., insensitivity to MK-801 blockade) in ovariectomized female mice. The rapidity of this neurochemical "switching" action of progesterone suggests mediation via cell surface receptors or the action of neuroactive steroid metabolites of progesterone.
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PMID:Acute progesterone can recruit sex-specific neurochemical mechanisms mediating swim stress-induced and kappa-opioid analgesia in mice. 1546 33