Articles: hyperalgesia.
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Cold hyperalgesia is a common side effect of oxaliplatin treatment; still, the pathophysiological and molecular mechanisms as well as the contribution of different primary afferent fiber systems are unclear. Therefore, patients with oxaliplatin-induced acute neuropathy with (n = 6) and without (n = 7) cold hyperalgesia were tested by applying a preferential blockade of peripheral myelinated A-fiber afferents in combination with quantitative sensory testing. Additionally, an interview-based questionnaire assessed the severity of symptoms and the impact on daily activities. ⋯ This suggests that oxaliplatin-induced cold hyperalgesia is mediated by A-fibers and that a deficit in A-fiber function might prevent the development of cold hyperalgesia. The work supports findings in rodents and in human sural nerve biopsies indicating that oxaliplatin interferes with axonal ion conductance in intact A-fibers by sensitizing potassium and/or sodium channels. Drugs that act on these molecular targets might be of potential value to treat oxaliplatin-induced cold hyperalgesia.
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Chronic stress produces maladaptive pain responses, manifested as alterations in pain processing and exacerbation of chronic pain conditions including irritable bowel syndrome. Female predominance, especially during reproductive years, strongly suggests a role of gonadal hormones. However, gonadal hormone modulation of stress-induced pain hypersensitivity is not well understood. ⋯ In addition, the presence of estradiol during stress increased spinal brain-derived neurotrophic factor (BDNF) expression independent of sex. In contrast, testosterone blocked the stress-induced increase in BDNF expression in female rats. These data suggest that estradiol facilitates and testosterone attenuates SIVH by modulating spinal excitatory and inhibitory glutamatergic receptor expression.
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Quantitative sensory testing after macroreplantation: evidence for a specific somatosensory profile.
A comprehensive functional recovery is one of the criteria for successful replantation of an amputated limb. Functionality of a replanted limb is strongly dependent on its regained sensibility. In previous studies concerning the sensibility of replanted limbs, only a few somatosensory submodalities were examined in small samples. ⋯ This distinct profile of impaired somatosensation shares some features of the somatosensory profile of neuropathic pain syndromes. Patients' limbs that were replanted many years before the present quantitative sensory testing showed more sensory deficits than patients with more recent replantations. This knowledge might be helpful in the development of more specific and more successful rehabilitation programs with replanted patients and improves the behavioral function of the replanted limb.
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Sickle cell disease (SCD) is a chronic inflammatory disorder accompanied by chronic pain. In addition to ongoing pain and hyperalgesia, vaso-occlusive crises-induced pain can be chronic or episodic. Because analgesics typically used to treat pain are not very effective in SCD, opioids, including morphine, are a primary treatment for managing pain in SCD but are associated with many serious side effects, including constipation, tolerance, addiction, and respiratory depression. ⋯ Our results show that intraperitoneal administration of MCC22 produced exceptionally potent dose-dependent antihyperalgesia as compared to morphine, dramatically decreased evoked responses of nociceptive dorsal horn neurons, and decreased expression of proinflammatory cytokines in the spinal cord. Moreover, tolerance did not develop to its analgesic effects after repeated administration. In view of the extraordinary potency of MCC22 without tolerance, MCC22 and similar compounds may vastly improve the management of pain associated with SCD.
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This study utilizes a model of long-term spinal cord stimulation (SCS) in experimental painful diabetic polyneuropathy (PDPN) to investigate the behavioral response during and after four weeks of SCS (12 hours/day). Second, we investigated the effect of long-term SCS on peripheral cutaneous blood perfusion in experimental PDPN. ⋯ We demonstrated that long-term SCS results in decreased baseline mechanical hypersensitivity and results in increased peripheral blood perfusion during stimulation in a rat model of PDPN. Together, these findings indicate that long-term SCS results in modulation of the physiological circuitry related to the nociceptive system in addition to symptomatic treatment of painful symptoms.