Articles: hyperalgesia.
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Opioids are extensively used as analgesics to control burn pain. However, systemic administration of opioids induces multiple adverse effects that are primarily CNS mediated. Alternately, topical application of low dose of opioids directly at the site of injury could attenuate pain while avoiding CNS-mediated side effects. ⋯ The anti-hyperalgesic effects were then measured (5, 15, 30, 60 and 120min post-drug application) using the Hargreaves' thermal test. All three opioids produced statistically significant increases in paw withdrawal latency (PWL), taken as a measure of anti-hyperalgesia, in comparison to saline-treated group (P<0.05), at both 4 and 7days post injury, with fentanyl showing greatest efficacy. Taken together, a low dose of topical application of opioids can reduce thermal hyperalgesia in a rat hindpaw FTTI model, supporting the development of topical formulations of these drugs for burn pain treatment in the clinic.
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Cisplatin is an effective chemotherapeutic agent indicated in cancer chemotherapy. However, its clinical use is associated with peripheral neuropathy that invariably impairs patient quality of life. Gabapentin (GBP) is an effective analgesic for neuropathic pain conditions but its clinical efficacy in cisplatin-induced neuropathic pain (CINP) is limited, in addition to generating unwanted side-effects. ⋯ In the rotarod paradigm, GBP at all doses markedly impaired motor performance, whilst GPS was devoid of motor incoordination except at the highest dose, when a mild impairment occurred. Salicylaldehyde alone had no effect on CINP or rotarod performance and neither was there any synergism when coadministered with GBP. These findings suggest that both GBP and GPS have beneficial effects in the neuropathic pain model though GPS may be potentially more useful in the management of CINP.
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Cebranopadol is a novel and highly potent analgesic acting via nociceptin/orphanin FQ peptide (NOP) and opioid receptors. Since NOP and opioid receptors are expressed in the central nervous system as well as in the periphery, this study addressed the question of where cebranopadol exerts its effects in animal models of chronic neuropathic pain. Mechanical hypersensitivity in streptozotocin (STZ)-treated diabetic rats, cold allodynia in the chronic constriction injury (CCI) model in rats, and heat hyperalgesia and nociception in STZ-treated diabetic and control mice was determined after intraplantar (i.pl.), intracerebroventricular (i.c.v.), or intrathecal (i.th.) administration. ⋯ After central administration of cebranopadol, antihyperalgesic efficacy is reached at doses that are not yet antinociceptive. This study shows that cebranopadol is effective after peripheral as well as central administration in nociceptive and chronic neuropathic pain. Thus, it may be well-suited for the treatment of chronic pain conditions with a neuropathic component.
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Bromodomain-containing protein 4 binds acetylated promoter histones and promotes transcription; however, the role of bromodomain-containing protein 4 in inflammatory hyperalgesia remains unclear. ⋯ Complete Freund's adjuvant triggers enhanced bromodomain-containing protein 4 expression, ultimately leading to the enhanced excitability of nociceptive neurons and thermal hyperalgesia. This effect is likely mediated by the enhanced expression of voltage-gated sodium channel 1.7.
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Lysophosphatidic acid (LPA) is a bioactive lipid that impacts neurological outcomes after neurotrauma by inhibiting neuroregeneration, promoting inflammation, and contributing to behavioral deficits. Blocking LPA signaling with a novel anti-LPA monoclonal antibody (mAb) is neuroprotective after traumatic brain injury (TBI) if given to injured animals whose blood-brain barrier (BBB) has been compromised. It is hypothesized that the anti-LPA mAb could improve chronic pain initiated by TBI. ⋯ Compared with control rats that received LT3114 but no TBI, TBI rats demonstrated significantly higher concentrations of intranasally administered LT3114 antibody in some tissues. In behavioral studies, a significant attenuation of mechanical allodynia after TBI was observed in the anti-LPA treatment group (P = 0.0079), when compared with vehicle controls within 14 days after TBI. These results suggest that intranasal application of the anti-LPA antibody directly accesses CNS sites involved in TBI-related pain and that this access attenuates pain sequelae to the neurotrauma.