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)

CSF from a patient with congenital indifference to pain was found to produce analgesia in the rat following intracerebroventricular injections. The analgesic effect was attenuated by pretreatment with naloxone suggesting the involvement of hyperactive endogenous opiate mechanisms in this patient.
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PMID:Intracerebroventricular injection of cerebrospinal fluid (CSF) from a patient with congenital indifference to pain induces analgesia in rats. 621 Feb 10

On the basis of data obtained from subprimates subjected to acute pain stimuli, it has been hypothesized that the suppression of chronic pain in man during stimulation in the periventricular region involves endogenous opioid mechanisms. However, there is at present no direct and unequivocal proof that the pain relief in man is necessarily and entirely dependent upon such mechanisms. There exist several putative substances with opiate-like properties but they are difficult to identify. The assay methods lack specificity and cross-reactions are common. There are only a few studies published on the influence of intracerebral stimulation in man on the CSF-content of opioid substances; the changes observed are inconsistent, and data are only given on patients having satisfactory pain relief. Furthermore, measurements have been made only during the course of a few hours and nothing is reported on the relationship between the changing concentrations of the substance and the level of pain. The observation that Naloxone may reverse the effect of intracerebral stimulation has become the keystone in postulating common mechanisms for stimulation-produced pain relief and morphine analgesia. The fact, that Naloxone is sometime ineffective or has to be used in huge, and unphysiological, doses is generally disregarded. There are a number of substances which may serve as neurotransmittors in pain transmission and pain inhibition but their mode of action in the generation and suppression of chronic pain is entirely unknown. Data collected from various European clinics covering more than 200 patients subjected to intracerebral stimulation show that the outcome of this treatment is highly unpredictable. Intracerebral stimulation as a clinically useful treatment of chronic pain can not be further developed unless hard data on its biochemical background in man are provided.
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PMID:Biochemistry of pain relief with intracerebral stimulation. Few facts and many hypotheses. 625 3

Fifteen patients undergoing thoracotomy were given 0.25 or 0.50 mg morphine intrathecally (L2-L3 or L3-L4) for an analgetic and pharmacokinetic study. Administration of morphine at the end of the operation resulted in a highly variable duration of analgesia ranging from 1-20.5 and 1-40 h for the 0.25 and 0.50 mg groups, respectively. Calculation of cumulative consumption pattern of additional analgesics given im indicated a dose-related analgesia lasting around 12 h. Morphine concentrations in the CSF were high and dose dependent. Thus, at 1 h, CSF concentrations (means +/- SEM) were 4,228 +/- 361 ng/ml and 10,447 +/- 1,538 ng/ml for the 0.25 and 0.50-mg groups, respectively. The plasma concentrations generally were very low, i.e., under 1 ng/ml. For the 0.50 and 0.25 mg groups, the terminal elimination half-life in CSF was 175 +/- 9 min and 196 +/- 13 min, respectively: the volume of CSF distribution was 0.88 +/- 0.16 ml X kg-1 and 1.06 +/- 0.17 ml X kg-1, respectively: and the clearance from CSF was 2.81 +/- 0.41 microliter X kg-1 X min-1 and 3.41 +/- 0.55 microliter X kg-1 X min-1, respectively (means +/- SEM). The study indicates that the significant pharmacokinetic parameter related to the long duration of analgesia after intrathecal morphine administration probably is the high CSF concentrations found, since the rate of elimination from CSF is similar to what is reported for morphine in plasma. Furthermore, modulation of nociceptive input in the thoracic region also may be achieved by lumbar administration, but a slower onset should be anticipated.
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PMID:Pharmacokinetic aspects of intrathecal morphine analgesia. 654 39

Epidural (E.D.) and intrathecal (I.T.) morphine (M) analgesia were studied in patients with pain after thoracotomy. The role of the pharmacokinetic properties of M. for the associated analgesia was also evaluated. M. concentrations in CSF and plasma were assayed using gas chromatography with EC detection. Analgesia was evaluated as the time postoperative until the patients again required analgetics and were given meperidine intramuscularly (I.M.) for thoracic pain. A lumbar site of E.D. and I.T. injection of M. resulted in a variable but in general longlasting postoperative analgesia although delayed after I.T. administration. The mean duration of analgesia after E.D. administration was dose-related (8.6 +/- 2.0 h, 13.0 +/- 3.5 h, and 15.6 +/- 2.6 h; means +/- SEM for the 2, 4 and 6 mg groups, respectively), which was comparable to that achieved after I.T. administration of 0.25 to 0.50 mg M. M. concentrations in plasma after E.D. administration were comparable in variability and magnitude to those found after I.M. administration. The concentrations of M. in plasma were not related to the long duration of analgesia and may only contribute to analgesia shortly after the E.D. administration. The reported time course of analgesia after E.D. injection with a delayed onset corresponded with the appearance of M. in the CSF. Fifteen min after E.D. administration, M. was found in higher concentrations in CSF than in plasma, but peak levels were not seen until 2 h after the injection. Both the high content of M. in CSF as expressed by AUC, as well as peak concentrations in CSF, were related to the longlasting analgesia after E.D. administration. A protracted clearance of M. from the CSF as a cause of longlasting analgesia was not found, M. was eliminated with a similar half-life from CSF and plasma. The high CSF concentrations of M. seen after E.D. administration were the result of a direct uptake across the dura. In contrast, the appearance of M. in CSF after I.M. administration of 10 mg was slower. Maximal concentration of M. in the CSF was reached after 3 h and the peak levels were on average about 100 times less than those found after E.D. injection of 6 mg morphine. CSF and plasma reached pseudoeliquilibrium at a ratio around 0.9 after I.M. administration. This is to be compared with a CSF/plasma concentration ratio around 100 after E.D. administration. A comparison of M. concentrations in the CSF after thoracic and lumbar E.D. injection showed that spinal CSF rapidly yielded comparable concentrations at the lumbar level.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pharmacokinetic aspects of spinal morphine analgesia. 658 39

Effective analgesia resulted from the injection of peridural meperidine in two groups of cancer patients, eight with postoperative pain and eight with intractable pain. Peridural meperidine HCl, 100 mg (n = 8), in 10 ml saline administered to patients following surgery was followed by a median duration of analgesia of 6 hours (range 4-20 hours) over periods ranging from 1-4 days. Peridural meperidine HCl, 30-100 mg (n = 8), in 10 ml saline administered to patients with intractable pain gave a median duration of analgesia of 8 hours (range 4-20 hours) over periods ranging from 1-9 days. There was no obvious tendency towards tolerance. In all patients, the onset of analgesia was within 5 min and was complete within 30 min. This analgesia paralleled the rise in CSF meperidine concentrations following peridural administration. Systemic absorption of peridurally administered meperidine occurred with a half-life of 15-30 min and produced blood concentrations high enough to contribute to analgesia after approximately 20 min in the majority of patients. There was no objective evidence in any neurological change nor sympathetic blockade after peridural meperidine. From this evidence the dorsal horn of the spinal cord may be the major site of action as distinct from the axonal blockade produced by local anesthetics, indicating 'selective' spinal analgesia.
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PMID:Peridural meperidine in humans: analgesic response, pharmacokinetics, and transmission into CSF. 729 5

Studies are described on the effect of plasma tryptophan changes on brain 5HT synthesis in man and rat. Results show that human brain 5HT synthesis is influenced by the supply of tryptophan to the brain. This is indicated by: (a) significant correlations between plasma free tryptophan and CSF 5HIAA concentrations; (b) raised cortical 5HT concentrations after infusing tryptophan. In rat experiments, determinations of brain tryptophan uptake from a bolus of plasma injected into the carotid artery showed: (a) increased uptake when bolus free tryptophan was raised and total tryptophan kept constant; (b) unchanged uptake when bolus free tryptophan was kept constant and total tryptophan decreased. Brain tryptophan uptake from a buffer bolus was decreased by large neutral amino acids. Plasma total tryptophan could be rapidly decreased and free tryptophan increased by briefly disturbing food deprived rats. When free tryptophan concentration rose markedly there was an associated increase of brain tryptophan and 5HT turnover. Studies of shock provoked analgesia in rats and cortical evoked potentials in man both suggest that physiological variations of serotonergic activity are sufficient to influence these measures. This raises the possibility that moderate changes of tryptophan supply to the brain could, in some circumstances, alter serotonergic activity.
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PMID:Influence of plasma tryptophan on brain 5HT synthesis and serotonergic activity. 731 2

The concentration of procaine in the CSF of 10 adult nonpregnant cows was determined after epidural injection of 5% procaine hydrochloride solution. Samples of CSF were removed through a catheter introduced into the subarachnoid space at the lumbosacral intervertebral space and advanced craniad to the same level as the epidural injection site. The position and the location of the catheter and spinal needle were confirmed radiographically. Segmental analgesia was achieved 8 to 20 minutes after completing the procaine hydrochloride injection and extended between spinal cord segments T12 and L3 on one or both sides of the animal. The average duration of analgesia, as determined by response to superficial and deep muscular pinpricks at the L1 dermatome, was 81.3 +/- 22.8 minutes (min-max, 45-127 minutes). The average subarachnoid concentration of procaine 10 minutes after epidural injection was 120.4 +/- 42.9 microgram/ml. The highest average procaine concentration recorded was 160.7 +/- 63.7 microgram/ml at 25.0 +/- 6.7 minutes after injection. Average procaine concentration was 47.8 +/- 13.5 microgram/ml at cessation of analgesia. A similar concentration of procaine was recovered from the subarachnoid space during either unilateral or bilateral analgesia. Procaine was not found in arterial plasma after the epidural administration of procaine hydrochloride. Subarachnoid threshold concentrations of local anesthetic necessary to produce spinal analgesia were reached after repeated epidural injections, but not after a single administration. It is concluded that segmental epidural analgesia is principally due to anesthesia of dura-covered nerve roots within and outside the epidural space and is minimally, if at all, dependent on the production of analgesia of nerves within the subarachnoid space.
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PMID:Appearance of procaine in spinal fluid during segmental epidural analgesia in cows. 733 26

Since there are several endogenous morphine-like substances differing in distribution and probably also in function, it seems necessary to study their roles in acupuncture analgesia separately. Therefore we set up a sensitive and specific radioimmunoassay (RIA) for met- and leu-enkephalin, and employ it in determining the changes of enkephalin contents in the brain regions and CSF during acupuncture. The main results are as follows: (i) Two enkephalins increase markedly in hypothalamus and striatum during acupuncture analgesia. (ii) Prior intraventricular bacitracin enhances the acupuncture analgesia with concomitant increased contents of enkephalins in the brain and CSF. (iii) Cycloheximide, the protein-synthesis inhibitor, reduces the enkephalin-increasing effect of acupuncture, indicating that one of the mechanisms by which acupuncture elevates the enkephalin levels is the acceleration of biosynthesis. (iv) After surgical isolation of rat hypothalamus, the effect of electric acupuncture is attenuated. This indicates that hypothalamus takes part in acupuncture analgesia.
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PMID:Enkephalin involvement in acupuncture analgesia-radioimmunoassay. 745 65

The present study was to investigate the effect of metoclopramide (MCP) on electroacupuncture analgesia (EAA) and its mechanism on a rabbit visceral pain model. The results showed that MCP 8mg/kg i.v. could potentiate EAA and prolong the analgesic duration. The potentiation effect could be attenuated by icv apomorphine (APO) (a mixed D1/D2 agonist). The analgesic duration was shortened by icv SKF38393 (a selective D1 agonist) or LY171555 (a selective D2 agonist). Using HPLC-ECD, we also found that the HVA content in CSF significantly increased at 20 min. after electroacupuncture (EA) or MCP 8mg/kg i.v. (P < 0.05), but the change of HVA content was not significant when EA and MCP 8mg/kg i.v. were used together. All these observations indicate that MCP have effects of potentiating EAA and prolonging analgesic duration. These effects are related to the blockade of the central DA receptor. The activations of D1 or D2 receptor is unfavourable to the expression of EA after effect.
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PMID:[Potentiation of electroacupuncture analgesia on visceral pain by metoclopramide and its mechanism]. 783 58

Simultaneous pharmacokinetic-pharmacodynamic (PK-PD) models of meperidine in goats were established by utilizing the P3 wave of the cerebral evoked potentials as an analgesic measurement. An effect compartment linked to the central compartment was postulated in the models. The hypothetical drug amount in the effect compartment was related to the observed analgesia through the Hill equation. After intramuscular (i.m., n = 16) and intravenous (i.v., n = 13) dosing (5 mg/kg), the elimination rate constants of meperidine in the effect compartment (Ke0) were 0.3744 +/- 0.2546 and 0.1123 +/- 0.0428 min-1, drug concentrations in the effect compartment generating half maximal analgesia (EC(50)) were 0.70 +/- 0.33 and 0.41 +/- 0.26 microgram/ml, the maximal effects (Emax) were 89.63 +/- 15.63 and 85.92 +/- 9.64%, and the Hill coefficients (S) were 2.61 +/- 1.21 and 2.37 +/- 1.15, respectively. Ke0 and EC(50) with i.m. dosing were significantly greater than with i.v. injection. However, administration route had no influence on S, Emax and the total amount of effect (AUE). The predicted peak effect (Emax) of 64.44 +/- 14.64 and 66.02 +/- 11.51% were achieved at 14.7 +/- 7.4 and 8.5 +/- 2.2 min after i.m. and i.v. dosing, respectively. Peak analgesia appeared much later than peak plasma concentration, but simultaneously with peak CSF level both after i.m. and i.v. dosing. An obvious hysteresis was demonstrated between plasma concentration and analgesic effect. This study demonstrates that meperidine analgesia can be predicted using a PK-PD model, but not by PK data alone. Both i.m. and i.v. administration routes were evaluated kinetically and dynamically.
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PMID:Pharmacokinetic-pharmacodynamic modelling of meperidine in goats (II): Modelling. 804 Sep 32


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