Articles: hyperalgesia.
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The mechanisms responsible for the persistence of chemotherapy-induced peripheral neuropathy (CIPN) in a significant proportion of cancer survivors are still unknown. Our previous findings show that CD8 T cells are necessary for the resolution of paclitaxel-induced mechanical allodynia in male mice. In this study, we demonstrate that CD8 T cells are not only essential for resolving cisplatin-induced mechanical allodynia, but also to normalize spontaneous pain, numbness, and the reduction in intraepidermal nerve fiber density in male and female mice. ⋯ Moreover, adoptive transfer of cisplatin-educated CD8 T cells to Rag2 mice prevented CIPN development induced by either cisplatin or paclitaxel, indicating that the activity of the educated CD8 T is not cisplatin specific. In conclusion, resolution of CIPN requires in vivo education of CD8 T cells by exposure to cisplatin. Future studies should examine whether ex vivo CD8 T cell education could be applied as a therapeutic strategy for treating or preventing CIPN in patients.
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Anesthesia and analgesia · Jun 2019
Attenuation of Unevoked Mechanical and Cold Pain Hypersensitivities Associated With Experimental Neuropathy in Mice by Angiotensin II Type-2 Receptor Antagonism.
Recent findings from a phase II clinical trial showed analgesic effects of an angiotensin II type-2 receptor (AT2R) antagonist in postherpetic neuralgia patients. This study aimed to investigate whether AT2R antagonism could provide effective analgesia in voluntary measures of unevoked/ongoing pain-like behaviors in mice with experimental neuropathy. Mice were subjected to spared nerve injury to induce neuropathy and tested in 2 operant behavioral tests to measure ongoing mechanical and cold pain hypersensitivities. Systemic administration of an AT2R antagonist provided effective analgesia in these behavioral measures of mechanical and cold pain in spared nerve injury mice, suggesting its effectiveness in neuropathic pain.
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Review Meta Analysis
Evidence of opioid-induced hyperalgesia in clinical populations after chronic opioid exposure: a systematic review and meta-analysis.
Opioid-induced hyperalgesia (OIH) is well documented in preclinical studies, but findings of clinical studies are less consistent. The objective was to undertake a systematic review and meta-analysis of studies examining evidence for OIH in humans after opioid exposure. ⋯ OIH was evident in patients after chronic opioid exposure, but findings were dependent upon pain modality and assessment measures. Further studies should consider evaluating both pain threshold and pain tolerance across a range of modalities to ensure assessment validity. Significant subgroup findings suggest that potential confounders of pain judgements, such as illicit substance use, affective characteristics, or coping styles, should be rigorously controlled in future studies.
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Reg Anesth Pain Med · Jun 2019
Fentanyl versus remifentanil-based TIVA for pediatric scoliosis repair: does it matter?
Opioid-induced hyperalgesia (OIH) and acute opioid tolerance have been demonstrated extensively in patients undergoing adolescent idiopathic scoliosis (AIS) repair. Remifentanil infusion has been strongly linked to both tolerance and OIH in these patients; however, the impact of using an intraoperative fentanyl infusion has not been well studied. This study aims to determine if patients undergoing operative management of AIS have decreased opioid consumption and pain scores when an intraoperative fentanyl infusion is used as compared with a remifentanil infusion. ⋯ Despite concerns for hyperalgesia and acute tolerance, remifentanil is widely used for intraoperative opioid infusions for surgical correction of AIS. This retrospective study examined a practice change from intraoperative remifentanil to intraoperative fentanyl as a potential approach to avoid OIH. Surprisingly, patients receiving fentanyl intraoperatively showed increased postoperative opioid use and pain scores in the first 24 hours postsurgery compared with the prior cohort receiving remifentanil. Substitution of fentanyl for remifentanil during surgical correction of AIS does not appear to solve the problem of OIH or acute tolerance. Prospective studies are needed to confirm this unexpected result.
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Cutaneous allodynia is a common clinical feature of migraine that has been associated with reduced efficacy of acute migraine treatments and an increased risk of disease progression. ⋯ In a representative sample of US adults with migraine, there were significant associations between allodynia and headache frequency and intensity, anxiety and/or depression, symptom severity, and acute medication overuse.