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At least 343 records · Page 19Linked to original sources
PubMed2001

Morphine and alternative opioids in cancer pain: the EAPC recommendations.

An expert working group of the European Association for Palliative Care has revised and updated its guidelines on the use of morphine in the management of cancer pain. The revised recommendations presented here give guidance on the use of morphine and the alternative strong opioid analgesics which have been introduced in many parts of the world in recent years. Practical strategies for dealing with difficult situations are described presenting a consensus view where supporting evidence is lacking. The strength of the evidence on which each recommendation is based is indicated.

Administration, Oral↗
PubMed2001

The use of thromboembolic deterrent stockings and a sequential compression device to prevent spinal hypotension during caesarean section.

Hypotension is a common side effect of spinal anaesthesia for caesarean section. We have performed a randomised, controlled study to determine the efficacy of a sequential compression device (SCD) (Kendall) in combination with thromboembolic deterrent (TED) stockings (Kendall) to reduce the incidence of hypotension in this setting. Within 20 min of spinal injection, there was no statistically significant difference in the incidence of hypotension (defined as less than 100 mmHg and less than 80% of baseline blood pressure) (TED/SCD group 65%, control 80%, P = 0.12). However, there was a trend for those receiving TED/SCD prophylaxis to require less ephedrine to maintain normotension than the control group (median TED/SCD 3 mg, control 6 mg, P = 0.08). The administration of ephedrine deviated from protocol on a total of 46 occasions (2.3% of recordings). To try to reduce the influence of this, we reinspected our data using time to first episode of hypotension with a Kaplan-Meier survival analysis. This showed that the instantaneous risk (hazard) of developing hypotension was 1.8 (95% CI: 1.1-2.9) times higher in controls than those receiving TED/SCD prophylaxis (P = 0.02). Despite demonstrating some benefit of TED/SCD prophylaxis to prevent hypotension, we do not consider that the magnitude of this benefit warrants their routine use.

Clinical Trial↗
PubMed1997

Covalent antithrombin-heparin complexes with high anticoagulant activity. Intravenous, subcutaneous, and intratracheal administration.

Although heparin has been used clinically for prophylaxis and treatment of thrombosis, it has suffered from problems such as short duration within compartments in vivo that require long term anticoagulation. A covalent antithrombin-heparin complex has been produced with high anticoagulant activity and a long half-life relative to heparin. The product had high anti-factor Xa and antithrombin activities compared with noncovalent mixtures of antithrombin and heparin (861 and 753 units/mg versus 209 and 198 units/mg, respectively). Reaction with thrombin was rapid with bimolecular and second order rate constants of 1.3 x 10(9) M-1 s-1 and 3.1 x 10(9) M-1 s-1, respectively. The intravenous half-life of the complex in rabbits was 2.6 h as compared with 0.32 h for similar loads of heparin. Subcutaneous injection of antithrombin-heparin resulted in plasma levels (peaking at 24-30 h) that were still detectable 96 h post-injection. Given the increased lifetime in these vascular and intravascular spaces, use of the covalent complex in the lung was investigated. Activity of antithrombin-heparin instilled into rabbit lungs remained for 48 h with no detection of any complex systemically. Thus, this highly active agent has features required for pulmonary sequestration as a possible treatment for thrombotic diseases such as respiratory distress syndrome.

Animals↗
PubMed2000

Contralateral but not systemic administration of bupivacaine reduces acute inflammation in the rat hindpaw.

The effects of contralateral treatment with local anesthetics following acute hindpaw inflammation were investigated in rats. Inflammation was induced by unilateral injection of either 50 or 100 microl of 1% carrageenan into the right paw. Contralateral injection of either bupivacaine or saline was given immediately before the carrageenan. Hindpaw edema and withdrawal responses to thermal and mechanical stimulation were evaluated after 3, 6 and 24h. The results showed that the pro-inflammatory effects of carrageenan were strongest at 6 h after the injection of 100 microl carrageenan with bilaterally decreased withdrawal latencies and ipsilateral edema formation. Contralateral treatment with bupivacaine (1.25, 2.5 or 5 mg/ml) dose-dependently reduced nociceptive behavior for 3-24h. The edema was also reduced at 6h. No effects on pain-related behavior were observed following systemic administration of bupivacaine. Sciatic nerve ligation on the contralateral side or intrathecal administration of saline significantly reduced the effects of bupivacaine when respectively compared with sham-operation and subcutaneous saline injection. Contralateral treatment with bupivacaine into the knee joint induced the same anti-nociceptive effect as administered into the paw. Our findings indicate that contralateral administration of bupivacaine induces long-lasting anti-nociceptive effects and may serve as a new or complementary treatment approach in acute inflammatory pain conditions.

Anesthetics, Local↗
PubMed1984

Evaluation of routes of administration of interferon in cancer: a review and a proposal.

Interferons are endowed with antiviral and antitumoral activities; the latter particularly has attracted attention, even though it remains uncertain whether it is preferentially due to a direct antiproliferative effect or to enhancement of host-mediated immune responses. Unfortunately, interferons administered in pharmacological doses produce considerable toxicity that is dose-related and that may require cessation of therapy. The administration of interferon has been carried out mostly by intravenous and intramuscular routes. High serum interferon titers have been expected to correlate with therapeutic efficacy. However, there is no such correlation, and certainly interferon levels in the interstitial fluid of target or effector cells would be more critical and informative. Moreover, because they are rapidly filtered by the kidneys, high serum titers are accompanied by considerable renal loss. Thus, several factors, one of which may be the unsuitability of administration routes, may explain the modest therapeutic efficacy of interferon so far observed in cancer. It must be emphasized that interferons and other biological response modifiers are pharmacodynamically unique substances able to elicit unpredictable responses; effects of these drugs depend on the nutritional and metabolic status and immune responsiveness of the host rather than simply on their plasma levels. After reviewing possible routes of administration, a new one, the lymphatic route, appears of interest. The basic strategy is to shift most of the interferon into the lymph pool minimizing direct absorption into the blood. In this way, the lymph/plasma ratio of interferon concentration will resemble that observed during the physiological response and will be greater than 1. Most of the injected interferon will then interact with the lymphoid system, even though eventually it will slowly drain into the blood pool. If the therapeutic index can be shown to be improved in patients, facilitated lymphatic absorption could become a preferential route for the administration of biological response modifiers.

Administration, Oral↗
PubMed2001

Intrathecal sufentanil and morphine for post-thoracotomy pain relief.

In this double-blind randomized study we compared a group of 15 patients undergoing thoracotomy who received a spinal injection of sufentanil 20 microg combined with morphine (200 microg) after induction of general anaesthesia with a control group of the same size. Post-operative pain was rated on a visual analogue scale (VAS) and a verbal rating scale at rest and with a VAS on coughing. In the recovery room, patients received titrated i.v. morphine until the VAS score was <30, and were followed by patient-controlled analgesia (PCA) for 72 h. The intrathecal sufentanil and morphine group had a lower intra-operative requirement for i.v. sufentanil and needed less i.v. morphine for titration in the recovery room. I.v. PCA morphine consumption and pain scores were lower in the active group than in the control group during the first 24 h. There were no differences after this time. Spirometric data (peak expiratory flow, forced vital capacity and forced expiratory volume in 1 s) were similar in the two groups. We conclude that the combination of intrathecal sufentanil and morphine produces analgesia of rapid onset and with a duration of 24 h.

Adult↗
PubMed1989

A study of the analgesic interaction between intrathecal morphine and subcutaneous nalbuphine in the rat.

Nalbuphine reverses opioid-induced respiratory depression, but the effect on analgesia is unclear. The analgesic interaction between subcutaneous (sc) nalbuphine and intrathecal morphine in conscious, male, Sprague-Dawley rats implanted with chronic intrathecal catheters was investigated. Nalbuphine (10 mg/kg) injected 30 min after intrathecal morphine (4 micrograms) significantly antagonized the effect of morphine in the tail flick test. The antagonism was rapid in onset and persisted beyond the experimental period of 240 min. The magnitude and the duration of the effect were comparable to that observed with sc naloxone (1 mg/kg). In contrast to the results in the tail flick test, nalbuphine enhanced the effect of intrathecal morphine in the noninflamed paw pressure test. Nalbuphine (10 mg/kg) alone had no effect on the time course of tail flick latency but significantly increased paw pressure threshold during the 15-90 min interval after sc injection. Nalbuphine (0.5 mg/kg, sc) alone had no antinociceptive effect in either pain test and did not antagonize the antinociceptive effect of intrathecal morphine (4 micrograms) in the tail flick test. However, sc nalbuphine (0.5 mg/kg), injected 30 min after intrathecal morphine (1.5 micrograms), significantly enhanced the effect of morphine in the paw pressure test compared with intrathecal morphine + sc saline-treated rats. The results indicate a complex analgesic interaction between intrathecal morphine and sc nalbuphine. The net analgesic effect during the interaction was determined by the following: 1) the doses of morphine and nalbuphine; 2) the time after nalbuphine administration; and 3) the nature of the nociceptive stimulus. At lower doses, sc nalbuphine appeared to potentiate the effect of intrathecal morphine in the noninflamed paw pressure test.

Analgesics↗
PubMed1996

Ketamine attenuates and reverses morphine tolerance in rodents.

BACKGROUND: The development of tolerance complicates the use of morphine to manage persistent pain. N-methyl-D-aspartate receptor antagonists can attenuate or reverse morphine tolerance. The authors studied ketamine's ability to modulate morphine tolerance. METHOD: Tolerance was produced in mice given morphine subcutaneously and was assessed by a cumulative dose-response analysis using the tail-flick test. The ability of ketamine at 0.3, 3, or 10 mg/kg given subcutaneously before and after morphine to attenuate the development of tolerance was assessed. The ability of 10 mg/kg ketamine to reverse tolerance produced by the subcutaneous implantation of morphine pellets to mice was also assessed. Rats were made tolerant to intraspinal morphine and the effects of the coadministration of 12 micrograms intraspinal ketamine were assessed. RESULTS: Morphine given subcutaneously produced a fivefold increase in the median effective (ED50) dose of morphine, which was dose-dependently attenuated by subcutaneously administered ketamine. A tenfold increase in the morphine ED50 produced by morphine pellets was completely reversed by ketamine given subcutaneously. Intraspinal morphine produced a 46-fold increase in its ED50, which was almost completely attenuated by the coadministration of intraspinal ketamine. CONCLUSIONS: Systemically administered ketamine attenuates and reverses systemically induced morphine tolerance in mice, and intraspinal ketamine attenuates tolerance produced by intraspinal morphine in rats.

Analgesia↗
PubMed1997

Effect of systemic and intrathecal morphine in a rat model of postoperative pain.

BACKGROUND: To learn more about persistent pain after an incision, a rat model for postoperative pain has been developed. To further evaluate this model, the authors examined the effect of intrathecal (IT) and subcutaneous (SC) morphine, effective for postoperative pain relief in patients, on pain behaviors immediately after surgery and 1 day after surgery. METHODS: Rats were anesthetized with halothane, and a 1-cm incision was made in the plantar aspect of the foot and closed. After recovery, the rats were placed on an elevated plastic mesh floor, and withdrawal threshold was determined using calibrated von Frey filaments (15-522 mN) applied from beneath the test cage to an area adjacent to the wound at the heel. Pain behaviors also were assessed using the response frequency to a nonpunctate mechanical stimulus and a cumulative pain score. RESULTS: Mechanical hyperalgesia and nonevoked pain behaviors were present on the day of surgery and 1 day after surgery. Administration of either SC (0.3-3.0 mg/kg) or IT (0.16-5.0 micrograms) morphine reversibly increased the withdrawal threshold. The response frequency to the nonpunctate stimulus and the nonevoked pain scores also were decreased by 3 mg/kg of SC or 5 micrograms of IT morphine. Naloxone (1 mg/kg) reversed morphine-produced hypoalgesia. CONCLUSION: This is the first study to demonstrate that mechanical hyperalgesia to a nonpunctate stimulus occurs after a surgical incision in the rat. This rat model of postoperative has several similarities to postoperative patients: mechanical hyperalgesia to punctate and nonpunctate stimuli, nonevoked pain, and pain behaviors inhibited by SC and IT morphine. This model also may be useful for predicting analgesia by investigational agents for postoperative pain.

Analgesics, Opioid↗
PubMed2002

Interleukin-2 gene has superior antinociceptive effects when delivered intrathecally.

The antinociceptive effect of interleukin-2 gene on rat carrageenan-induced pain was explored using different delivery methods. Intrathecal (i.t.) or plantar s.c. delivery of plasmid harbouring the interleukin-2 gene produced a marked antinociceptive effect, which was maintained up to 6 days; the administration of recombinant human interleukin-2 only had a transitory effect. The antinociceptive effect lasted longer and was more potent when the interleukin-2 gene was administered i.t. than when delivered s.c. The effect of the interleukin-2 gene was related to its protein expression, was dose dependent, and could be potentiated by liposome. The results suggest that the interleukin-2 gene has a good prospect for clinical use.

Afferent Pathways↗
PubMed1988

The pain of discography.

Lumbar discography is a commonly employed diagnostic tool, but important questions about it remain unresolved. Why is an abnormal discogram painful in one patient and not in another? This study was performed to investigate the changes in Substance P (SP) and Vasoactive-Intestinal Peptide (VIP), found in the dorsal root ganglion, following discography in normal and abnormal canine lumber intervertebral discs. The data from this study suggest that dorsal root ganglion SP and VIP are indirectly affected by manipulations of the intervertebral disc. It may be that various neurochemical changes within the intervertebral disc are expressed by sensitized (injured) annular nociceptors, and in part modulated by the dorsal root ganglion. Therefore, the concomitant pain sometimes associated with an abnormal discogram image may in part be related to the chemical environment within the intervertebral disc and the sensitized state of its annular nociceptors.

Animals↗
PubMed1991

Clinical pharmacokinetics of morphine.

Morphine (M) is recommended by the World Health Organization as the treatment of choice for moderate-to-severe cancer pain. Development of sensitive radioimmunoassays (RIA) and high-performance liquid chromatography in the past 20 years has allowed study of the pharmacokinetics of M, which remain incompletely understood. Data derived by RIA must be interpreted with caution due to cross-reactivity with anti-sera by metabolites, impairing assay specificity. The pharmacokinetics of M have been determined for various clinical situations, but there is large interpatient variability for most parameters. M is readily absorbed from all routes of administration, except transdermal, and it can be injected spinally. Peak plasma levels are achieved within 15-20 min of intramuscular and subcutaneous administration, and within 30-90 min after oral. Peak levels after oral administration are much lower than after parenteral routes, since oral M undergoes extensive first-pass metabolism in the liver. With repeated administration, the oral-parenteral relative potency ratio is 1:3 M can be administered epidurally or intrathecally and has also been given intracerebroventricularly. Epidural M enters the subarachnoid space, but is also absorbed into the systemic circulation. Only 5% of a dose crosses the dura. M administered in the lumbar region is quickly redistributed in the cerebrospinal fluid in a rostral direction, explaining the high incidence of systemic side effects following spinal administration. After absorption, M is rapidly and widely distributed and crosses the blood-brain barrier. With therapeutic doses, plasma protein binding is only 20-35%, and the volume of distribution is 1-6 L/kg. The primary site of M metabolism is the liver, and the dose should be reduced in patients with liver disease. Glucuronidation is the main metabolic pathway, but the principal metabolite, morphine-3-glucuronide (M3G), is inactive. Morphine-6-glucuronide (M6G) is produced in smaller amounts than M3G, but is pharmacologically active and many times more potent than M. The ratio of M6G to M in plasma, after a dose of M, is approximately 10:1, and the ratio does not change with increasing doses or prolonged treatment. Normorphine (NM) is also active, and is formed to a greater extent after oral administration; it is not, however, usually found in plasma. NM may be neurotoxic. M and its metabolites are excreted by the kidney, but urinary free M accounts for less than 10% of an administered dose. In patients with renal insufficiency, the metabolites accumulate, though M itself is still excreted.(ABSTRACT TRUNCATED AT 400 WORDS)

Biotransformation↗
PubMed2005

Incision of the intervertebral disc induces disintegration and increases permeability of the dorsal root ganglion capsule.

STUDY DESIGN: The origin and the barrier properties of the characteristic reaction at the surface of the dorsal root ganglion (DRG) exposed to the nucleus pulposus was studied using Alcian-Blue staining, van Gieson staining, and the application of Evans Blue Albumin (EBA) complex in rats. OBJECTIVE: To study the origin and the barrier properties of the capsule, including the characteristic reaction, at the surface of the DRG exposed to the nucleus pulposus. SUMMARY OF BACKGROUND DATA: Local application of nucleus pulposus may induce a characteristic reaction at the surface of the DRG. This reaction histologically resembles an acute inflammatory reaction. However, it is not evident if this is a swelling of the DRG capsule, if it is located between the capsule and neurons of the DRG, or if it is only an attached nucleus pulposus. METHODS: Nucleus pulposus from the discs was obtained. The nucleus pulposus was smeared on glass slides. Alcian-Blue with hematoxylin and eosin staining was performed for each smear. Herniation of the nucleus pulposus was made in the L4-L5 disc in rats. The L4 DRGs were resected 3, 24, and 72 hours after surgery, and sectioned. The sections were processed for Alcian-Blue staining, van Gieson staining, and EBA complex infiltration. The sections were observed using light or fluorescent microscopy. RESULTS: Smear of nucleus pulposus was stained bright blue indicating mucins. A characteristic reaction, "inflammatory crescent," was confirmed at the surface of the DRG exposed to the nucleus pulposus. No mucins were observed in the crescent using Alcian-Blue. The results of van Gieson staining showed that the reaction started both inside and outside the elastic fiber layer, the DRG capsule, within 3 hours. The EBA complex was capable of infiltrating into the DRG capsule 24 hours after disc incision. CONCLUSIONS: The disintegrated capsule showed an increased permeability even for a large molecule as albumin, which indicates a possible entrance route for various substances induced by locally applied nucleus pulposus.

Animals↗
PubMed2006

Nonspondylolytic etiologies of lumbar pain in the young athlete.

Approximately 50% of adolescent athletes with persistent lumbar pain can be diagnosed with spondylolysis or spondylolisthesis. The remaining 50% will have suffered injury of the vertebral body, intervertebral disc, ring apophysis, pelvis, articular processes, spinous processes, interspinous ligament, or other soft tissues of the lumbar spine. The adolescent spine is prone to these injuries as a consequence of the growth spurt and skeletal immaturity. Accurate diagnosis is mandatory in order to achieve successful treatment. History, physical examination, imaging modalities, and precision spinal injections can be employed to accurately diagnose the source of the symptoms. Appropriate treatment measures can then be prescribed to optimally treat the adolescent spine injury.

Adolescent↗
PubMed2004

Comparison of transthecal digital block and traditional digital block for anesthesia of the finger.

A randomized, double-blind study was performed in 50 patients to compare the transthecal and traditional subcutaneous infiltration techniques of digital block anesthesia regarding the onset of time to achieve anesthesia and pain during the infiltration. All the patients had sustained injury involving two or four fingers of the hand. Each patient served as his or her own control, having one finger infiltrated with the transthecal technique and the other with the subcutaneous infiltration technique. Time to loss of pinprick sensation and pain (at the time of the infiltration and 24 hours postoperatively) were assessed using a visual analogue scale and verbal response score. A total of 104 blocks (52 transthecal and 52 subcutaneous infiltration) were performed. All of these blocks were successful. Mean time to achieve anesthesia with the transthecal block was 165 seconds, compared with 100 seconds for the subcutaneous infiltration block. The mean analogue pain score was higher for transthecal blocks than for subcutaneous infiltration blocks (3.2 +/- 0.19 versus 1.6 +/- 0.14). Twenty-four hours postoperatively, 24 patients who had the transthecal block experienced pain at the injection site of the digit. However, none of the patients who received the subcutaneous infiltration block complained of pain at the digit. The technique of anesthesia preferred by patients for their finger was the subcutaneous infiltration block, because it causes less pain. Our results confirm the efficacy of the transthecal block for achieving anesthesia of the finger; however, because it is a more painful procedure, it is not recommended.

Adolescent↗