Pain
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Randomized Controlled Trial Comparative Study Clinical Trial
Comparative efficacy of patient-controlled administration of morphine, hydromorphone, or sufentanil for the treatment of oral mucositis pain following bone marrow transplantation.
A total of 119 bone marrow transplant patients suffering from oral mucositis pain were enrolled in a randomized, double-blind, parallel-group trial comparing the efficacy of patient-controlled analgesia with morphine, hydromorphone and sufentanil. Patient ratings of pain and side-effects on visual analog scales were gathered daily from the start of patient-controlled analgesia (PCA) therapy until the discontinuation of opioid treatment either because of resolution of oral mucositis pain, intolerable side-effects, inadequate pain control, or complications related to transplantation. Of the 119 enrolled subjects, 100 met the evaluable criteria of developing oral mucositis and remaining on the study for at least 2 days. ⋯ Morphine consumption reached a plateau by day 5, whereas hydromorphone and sufentanil consumption continued to rise until days 7 and 9, respectively. Sufentanil dose requirement increased by approximately 10-fold compared to morphine and hydromorphone, whose requirements increased only 5-fold, suggesting the possibility of development of acute pharmacological tolerance in some patients with this phenylpiperidine opioid. This study provides support for the recommendation that morphine is the opioid of first choice when patient-controlled analgesia is employed for the treatment of severe oropharyngeal pain in bone marrow transplantation (BMT) patients.
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Anaesthetists, using basic scientific concepts of peripheral opioid activity, try to improve regional anaesthesia and postoperative analgesia by injecting opioids, with or without local anaesthetic, close to nerve trunks or nerve endings. To test the evidence that peripherally applied opioids (all except intra-articular) have an analgesic effect outside the knee joint. Systematic search for published reports of randomised controlled trials in the period 1966-1996 (MEDLINE, EMBASE, Oxford Data Base, reference lists) which compared efficacy of peripheral opioids with placebo, local anaesthetic, or systemic opioids in acute pain. ⋯ Trials of lower quality were more likely to report increased efficacy with opioids. Adverse events related to the route of administration were not reported. These trials provide no evidence for a clinically relevant peripheral analgesic efficacy of opioids in acute pain.
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The significance of preamputation pain for the development of postamputation stump and phantom pain has been discussed over the years and is still a matter of dispute. It has been argued that preamputation pain increases the risk of phantom pain and that phantom pain is a revivification of pain experienced before the amputation. The purpose of this prospective study was to clarify the relation between preamputation pain and phantom pain. ⋯ About 42% of the patients reported that their phantom pain resembled the pain they had experienced at the time of the amputation. However, there was no relation between the patients' own opinion about similarity between preamputation pain and phantom pain and the actual similarity found when comparing pre- and postoperative recordings of pain. Patients significantly overestimated preamputation pain intensity after 6 months.
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The antinociceptive effects of the combination of spinal morphine and gabapentin were evaluated in the tail-flick test in rats. The intrathecal coadministration of a subantinociceptive dose of morphine at 0.2 microgram and gabapentin at 300 micrograms produced significant antinociception. Pretreatment with spinal gabapentin at 300 micrograms shifted the dose-response curve of spinal morphine to the left with a decrease in morphine ED50 value from 1.06 micrograms to 0.34 microgram. ⋯ Furthermore, the concurrent administration of spinal naloxone at 30 micrograms with the combination of morphine and gabapentin blocked antinociception, while the concurrent administration of spinal bicuculline at 0.3 microgram failed to prevent antinociception. These results indicate that the combination of spinal gabapentin and morphine produces an enhancement of antinociception that appears to involve the spinal mu opioid receptors. Furthermore, repeated administration of gabapentin for 3 days did not affect the enhancing effect of gabapentin on the antinociceptive effect of morphine, indicating that tolerance did not develop to gabapentin's ability to enhance morphine antinociception.
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The blockade of spinal glycine receptors with intrathecal (i.t.) strychnine produces segmentally-localized allodynia in the rat; a reversible and highly reproducible effect that is attained without peripheral or central nerve injury. We investigated the effect of i.v. mexiletine, an orally active congener of lidocaine, on strychnine allodynia and compared the dose-response relationship of mexiletine in normal (noxious paw pinch) versus abnormal (i.t. strychnine) nociceptive conditions. In addition, we determined the dose-response effect of i.t. ⋯ AP-7 consistent with a spinal site of action. The data indicate that: (i) robust allodynia can be selectively induced with i.t. strychnine in animals whose somatosensory systems are otherwise normal; (ii) sub-anesthetic doses of i.v. mexiletine inhibit the abnormal responses to low-threshold (A-fiber) afferent input in the strychnine model of allodynia (i.e., in the absence of peripheral or central nerve injury) at doses which affect normal nociception; and (iii) in the presence of i.t. strychnine, low-threshold afferent input activates a spinal NMDA-receptor mediated process normally restricted to noxious afferent input. Systemic mexiletine may have an important spinal site of action in abnormal pain states.