Annals of neurology
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Annals of neurology · Dec 2008
Comparative StudyMultiple sodium channel isoforms and mitogen-activated protein kinases are present in painful human neuromas.
Although axons within neuromas have been shown to produce inappropriate spontaneous ectopic discharges, the molecular basis for pain in patients with neuromas is still not fully understood. Because sodium channels are known to play critical roles in neuronal electrogenesis and hyperexcitability, we examined the expression of all the neuronal voltage-gated sodium channels (Nav1.1, Nav1.2, Nav1.3, Nav1.6, Nav1.7, Nav1.8, and Nav1.9) within human painful neuromas. We also examined the expression of two mitogen-activated protein (MAP) kinases, activated p38 and extracellular signal-regulated kinases 1 and 2 (ERK1/2), which are known to contribute to chronic pain, within these human neuromas. ⋯ These results demonstrate that multiple sodium channel isoforms (Nav1.3, Nav1.7, and Nav1.8), as well as activated p38 and ERK1/2 MAP kinases, are expressed in painful human neuromas, indicating that these molecules merit study as possible therapeutic targets for the treatment of pain associated with traumatic neuromas.
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Annals of neurology · Dec 2008
Comparative StudyThe common inhalation anesthetic isoflurane induces caspase activation and increases amyloid beta-protein level in vivo.
An estimated 200 million patients worldwide have surgery each year. Anesthesia and surgery have been reported to facilitate emergence of Alzheimer's disease. The commonly used inhalation anesthetic isoflurane has previously been reported to induce apoptosis, and to increase levels and aggregation of Alzheimer's disease-associated amyloid beta-protein (Abeta) in cultured cells. However, the in vivo relevance has not been addressed. ⋯ Given that transient insults to brain may lead to long-term brain damage, these findings suggest that isoflurane may promote Alzheimer's disease neuropathogenesis and, as such, have implications for use of isoflurane in humans, pending human study confirmation.