Pain
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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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Clinical Trial Controlled Clinical Trial
Peripheral alpha-adrenoreceptors are involved in the development of capsaicin induced ongoing and stimulus evoked pain in humans.
While the sympathetic nervous system seems to be involved in some pain states, the mechanisms linking the sensory and sympathetic nervous system are unclear. In this study the possible involvement of peripheral alpha-adrenoreceptors in the development of capsaicin induced ongoing pain and mechanical hypersensitivity was examined in humans. Intradermal capsaicin injections in the volar aspect of the arm gave rise to ongoing burning pain and dysesthesia as well as mechanical hypersensitivity. ⋯ The area in which pain could be evoked on the phentolamine injected side was restricted to the area of flare and was significantly smaller than on the saline injected side. Mechanical stimulation gave rise to aftersensation and radiation of pain on the saline injected side in all subjects but only in one case on the phentolamine injected side. Peripheral alpha-adrenoreceptors thus seem to be involved in functional changes of primary afferents which contribute to ongoing pain and mechanical stimulus evoked pain.
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The presence of bone metastases predicts the presence of pain and is the most common cause of cancer-related pain. Although bone metastases do not involve vital organs, they may determine deleterious effects in patients with prolonged survival. Bone fractures, hypercalcaemia, neurologic deficits and reduced activity associated with bone metastases result in an overall compromise in the patient's quality of life. ⋯ Invasive techniques are rarely indicated, but may provide analgesia in the treatment of pain resistant to the other modalities. Neural blockade should never be used as the sole modality for malignant bone pain, but should be considered as a helpful in specific pain situations. Careful appraisal and the application of a correct approach should enable the patient with bone metastases to obtain an acceptable pain relief despite the advanced nature of their malignant disease.
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The effects of mexiletine, desipramine and fluoxetine in rat models involving central sensitization.
Drugs that are clinically effective (mexiletine and desipramine) or ineffective (fluoxetine) in the treatment of human neuropathic pain were evaluated for efficacy in rat models involving central sensitization (i.e., formalin model and the L5/L6 spinal nerve ligation model of neuropathic pain) using tests that differ in stimulus modality: noxious chemical stimulus (formalin model) as well as noxious (pin prick) and innocuous mechanical stimuli (application of von Frey filaments). Mexiletine (10-100 mg/kg, s.c.) significantly (P < 0.05) attenuated hyperalgesia in formalin-treated (60 mg/kg and 100 mg/kg) and neuropathic rats (100 mg/kg) as well as tactile allodynia in neuropathic rats (100 mg/kg). Desipramine (1-100 mg/kg, s.c.), on the other hand, reduced hyperalgesia significantly (P < 0.05) in formalin-treated (3, 10, 30 and 100 mg/kg) and neuropathic rats (10 mg/kg and 100 mg/kg), but did not reduce tactile allodynia in the neuropathic rats. ⋯ Thus, drugs which are effective in reducing human neuropathic pain consistently attenuated hyperalgesia in formalin-treated or neuropathic rats. Desipramine also distinguished mechanical hyperalgesia from tactile allodynia in rats rendered neuropathic by spinal nerve ligation. These data are consistent with the hypothesis that the neuronal mechanisms underlying these two manifestations of neuropathic pain are different.