The Journal of pharmacology and experimental therapeutics
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J. Pharmacol. Exp. Ther. · May 1999
Enhancement mu opioid antinociception by oral delta9-tetrahydrocannabinol: dose-response analysis and receptor identification.
The antinociceptive effects of various mu opioids given p.o. alone and in combination with Delta-9-tetrahydrocannabinol (Delta9-THC) were evaluated using the tail-flick test. Morphine preceded by Delta9-THC treatment (20 mg/kg) was significantly more potent than morphine alone, with an ED50 shift from 28.8 to 13.1 mg/kg. Codeine showed the greatest shift in ED50 value when administered after Delta9-THC (139.9 to 5.9 mg/kg). ⋯ We find that many mu opioids are enhanced by an inactive dose of Delta9-THC p.o. The exact nature of this enhancement is unknown. We show evidence of involvement of mu and possibly delta opioid receptors as a portion of this signaling pathway that leads to a decrease in pain perception.
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J. Pharmacol. Exp. Ther. · May 1999
Randomized Controlled Trial Clinical TrialProlonged analgesic effect of ketamine, an N-methyl-D-aspartate receptor inhibitor, in patients with chronic pain.
We examined the role of N-methyl-D-aspartate (NMDA) receptors in chronic (pathological) pain in humans by using the NMDA receptor antagonist ketamine as a probe. Thirty patients with neuropathic pain in the trigeminal area were given an i.m. injection of ketamine 0.4 mg/kg combined with midazolam 0.05 mg/kg. Pethidine 1.0 mg/kg served as a control. ⋯ These findings indicate that NMDA receptors are involved in the perception and maintenance of pathological pain in some patients. In others, pain appears to be mediated by NMDA receptor-independent mechanisms. We suggest that NMDA receptor-independent transmission in central pain pathways may contribute to the reduced efficiency of analgesic drugs often seen in chronic pain states.
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J. Pharmacol. Exp. Ther. · May 1999
Comparative StudyCerebrospinal fluid bioavailability and pharmacokinetics of bupivacaine and lidocaine after intrathecal and epidural administrations in rabbits using microdialysis.
The aim of this work was to study the cerebrospinal fluid (CSF) bioavailability and pharmacokinetics of bupivacaine (BUP) and lidocaine (LID) administered separately in rabbits using microdialysis with retrodialysis calibration. Microdialysis probe and catheters were inserted under control of the view in the intrathecal or epidural spaces. The epidural disposition of BUP and LID after epidural administration of low (0.69 microM) and high (6.9 microM) doses was studied. ⋯ After intrathecal administration, the plasma concentrations were below the limit of quantitation. Although the absorption rate of BUP appeared higher than that of LID, the mean CSF bioavailability of epidural BUP and LID was 5.5 and 17.7%, respectively. The unexpectedly higher CSF bioavailability of LID, the less lipophilic drug, may result from the difference in the processes competing for drug epidural removal.
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J. Pharmacol. Exp. Ther. · May 1999
Comparative StudySensitivity to the discriminative stimulus and antinociceptive effects of mu opioids: role of strain of rat, stimulus intensity, and intrinsic efficacy at the mu opioid receptor.
Effects of low (butorphanol, nalbuphine)-, intermediate (buprenorphine)-, and high (morphine, levorphanol)-efficacy mu opioids were examined in F344, Sprague-Dawley (SD), Long-Evans (LE), and Lewis rats using a tail withdrawal and a drug discrimination procedure. In the tail withdrawal procedure using low (50 degrees C), intermediate (52 degrees C), and high (56 degrees C) water temperatures, morphine and levorphanol produced maximal effects in each of the strains and were most potent in F344 and least potent in Lewis. Similar differences across strains were obtained with buprenorphine, and at the high intensity, maximal effects were not obtained in Lewis. ⋯ The magnitude of these differences increased with higher stimulus intensities and when tested with lower efficacy opioids. In rats trained to discriminate morphine (3.0 or 5.6 mg/kg) from water, there were no consistent differences across rat strains to the effects of these mu opioids. Possible reasons for differences between the results obtained in the tail withdrawal and drug discrimination procedures are discussed.
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J. Pharmacol. Exp. Ther. · May 1999
Spinal blockade of opioid receptors prevents the analgesia produced by TENS in arthritic rats.
Transcutaneous electrical nerve stimulation (TENS) is commonly used for relief of pain. The literature on the clinical application of TENS is extensive. However, surprisingly few reports have addressed the neurophysiological basis for the actions of TENS. ⋯ Spinal blockade of delta opioid receptors dose-dependently prevented the antihyperalgesia produced by high-frequency TENS. In contrast, blockade of kappa opioid receptors had no effect on the antihyperalgesia produced by either low- or high-frequency TENS. Thus, low-frequency TENS produces antihyperalgesia through mu opioid receptors and high-frequency TENS produces antihyperalgesia through delta opioid receptors in the spinal cord.