Pain
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An animal model showing mechanical allodynia following systemic bolus injection of a human/mouse chimeric monoclonal antibody to the GD2 ganglioside (ch14.18) has been established (e.g. pain behavior generated by a light tactile stimulus). This is of clinical relevance since ch14.18 is a promising experimental treatment for pediatric neuroblastoma. The present study examined the hypothesis that allodynic effects of the anti-GD2 antibody are mediated by actions on cutaneous nerve fibers. ⋯ Mean mechanical threshold for A delta fibers in all three antibody treated groups was significantly reduced compared to the saline control; this was not observed for C-fibers in any group. Intravenous bolus injection (15 mg/kg) and infusion of lidocaine (plasma level 0.3-2.2 micrograms/ml) both reduced anti-GD2 associated BA. These data demonstrate that mechanical-allodynia could be produced by action(s) of the anti-GD2 antibody (direct or indirect) on peripheral nerves and suggest intravenous lidocaine as part of the analgesic regimen accompanying anti-GD2 antibody treatment.
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A previously established relationship for deriving dichotomous from continuous information in randomised controlled trials (RCTs) of analgesics has been tested using an independent data set. Individual patient information from 18 RCTs of parallel-group design in acute postoperative pain (after abdominal, gynaecological and oral surgery) was used to calculate the percentage of the maximum possible pain relief score (%maxTOTPAR) and the proportion of patients with > 50%maxTOTPAR for the different treatments. The relationship between the measures was investigated in 85 treatments with over 3400 patients. ⋯ Reports of RCTs of analgesics frequently describe results of studies in the form of mean derived indices, rather than using discontinuous events, such as number or proportion of patients with 50% pain relief. Because mean data inadequately describe information with a non-normal distribution, combining mean data in systematic reviews may compromise the results. Showing that dichotomous data can reliably be derived from mean data in acute pain studies enables data published as means to be used for quantitative systematic reviews which require data in dichotomous form.
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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.