Pain
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A 62-year-old man receiving subcutaneous fentanyl for the management of cancer pain developed generalized central excitation after an overdose of 5000 micrograms of fentanyl. The patient developed acute confusion, restlessness, generalized myoclonus, visual hallucinations, and hyperalgesia and tremors upon tactile stimulation of the arms or legs. ⋯ Within an hour the symptoms reappeared and once again, responded immediately after a second injection of 0.2 mg of naloxone. Our findings suggest that fentanyl overdose can occasionally present with general central irritability that responds to naloxone.
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The opioid antagonist, naloxone, produces equivocal effects on the magnitude of nociceptive responses in several animal models of persistent pain, including the formalin test. Hindpaw injection of dilute formalin produces not only inflammation but also phasic (Phase 1) and persistent (Phase 2) behavioral and cardiovascular nociceptive responses in the rat. ⋯ Although the 100 mg/kg per h dose significantly decreased these responses, it also produced muscle rigidity and profound bradycardia. We conclude that endogenous opioids do not significantly modulate the nociceptive processing induced by subcutaneous formalin.
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Randomized Controlled Trial Clinical Trial
Effect of adrenergic receptor activation on post-herpetic neuralgia pain and sensory disturbances.
Patients with acute herpes zoster, and to a lesser extent post-herpetic neuralgia (PHN), have been reported to respond to local anesthetic blockade of the sympathetic nervous system. In animal models of nerve injury, local injection of adrenergic agonists after nerve injury, but not before, excites nociceptors. In some patients with chronic neuropathic pain, local application of norepinephrine evokes pain. ⋯ After injection of the adrenergic agonist into PHN skin, both overall PHN pain and allodynia severity were significantly greater than after saline injection, peaking at 10-15 min post-injection. Even when PHN has been present for years, adrenergic receptor stimulation in PHN skin increases pain, most likely through direct activation of C-nociceptors in the painful skin. Increased allodynia is most likely mediated centrally and driven by the increase in C-nociceptor input.
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This open prospective study evaluated the combination of initial dose titration with patient-controlled analgesia (PCA) and long-term treatment with transdermal fentanyl in 50 cancer patients requiring opioids for severe pain. The delivery rate of the first transdermal therapeutic system (TTS) was calculated from the self-administered intravenous fentanyl dose during the first 24 h. TTS were changed every 48-72 h, and a different patch size was chosen if necessary. ⋯ Other severe side-effects were not observed. Patient compliance and acceptance were excellent. The results suggest that intravenous PCA is useful for initial dose finding, and transdermal fentanyl is effective and safe during long-term treatment of cancer pain.
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Injection of formalin in the rat hindpaw produces two phases of nociceptive behavior. Although it is generally agreed that the first phase results from direct chemical activation of nociceptive primary afferent fibers, the factors that contribute to the second phase are not established. In the present study, we monitored the expression of the c-fos protein to evaluate whether the pattern of activity of dorsal horn neurons differs as a result of ongoing afferent activity during the two phases. ⋯ We did not observe further significant decreases when both remifentanil and lidocaine, or bupivacaine and lidocaine were injected (69.7% and 74.6%, respectively). Our results not only provide strong evidence that activity during the second phase is necessary for maintaining the maximal expression of c-fos in the spinal cord, but also reveal significant regional differences in the central patterns of activity generated during the two phases. These results also confirm our previous reports that c-fos expression is not eliminated when the behavioral manifestation of the noxious stimulus is completely blocked.