Neuroscience letters
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Neuroscience letters · Oct 2012
Dexmedetomidine decreases hyperalgesia in neuropathic pain by increasing acetylcholine in the spinal cord.
The activation of α2-adrenoceptors has attracted attention as a therapeutic target for neuropathic pain, which remains a clinical challenge. In the present study, we examined the interaction between α2-adrenergic and cholinergic signaling in a rat model of neuropathic pain induced by spinal nerve ligation (SNL). Intrathecal administration of dexmedetomidine, which is a selective α2-adrenoceptor agonist (0.1-1.0 μg), dose-dependently suppressed hyperalgesia in SNL rats but did not alter paw withdrawal thresholds in normal rats. ⋯ The combination of an ineffective dose of intrathecal dexmedetomidine with intraperitoneal donepezil, which is a cholinesterase inhibitor, decreased neuropathic hypersensitivity. These results suggest that plasticity of the spinal noradrenergic-cholinergic axis only occurs in neuropathic pain states. Thus, drug combinations that strengthen the noradrenergic-cholinergic interaction may provide therapeutic benefit in neuropathic pain.
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Neuroscience letters · Oct 2012
Cell degeneration is not a primary causer for Connexin26 (GJB2) deficiency associated hearing loss.
Connexin26 (Cx26, GJB2) mutations can induce congenital deafness and are responsible for ∼50% of nonsyndromic hearing loss in children. Mouse models show that Cx26 deficiency induces cochlear development disorder, hair cell loss, and spiral ganglion (SG) neuron degeneration. Hair cell loss and cell degeneration have been considered as a primary causer responsible for Cx26 deficiency associated hearing loss. ⋯ Functional tests show that hair cells in Cx26 KO mice functioned normally; outer hair cells retained electromotility. These data suggest that cell degeneration is not a primary causer of Cx26 deficiency associated hearing loss. Some mechanisms other than cell degeneration, such as cochlear development disorders, may play an essential role in this common hereditary deafness.
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Neuroscience letters · Oct 2012
P2X3 receptor mediates ectopic mechanical allodynia with inflamed lower lip in mice.
Ectopic pain in other orofacial regions develops with local inflammation in separated orofacial structures. However, the basis for the spreading of pain to adjacent orofacial areas after local inflammation is still unknown. In the present study, we determined if the P2X(3) receptor (P2X(3)R) was associated with altered mechanical sensitivity of the whisker pad skin following complete Freund's adjuvant (CFA) injection into the lower lip. ⋯ CGRP protein expression in TG ipsilateral to CFA injection was also significantly greater than that of the saline-injected mice. The present findings suggest that induced CGRP by local inflammation in the lower lip increases P2X(3)R in TG neurons, the increased P2X(3)Rs are involved in the sensitization of primary afferent neurons in the whisker pad skin. This P2X(3)R overexpression may underlie ectopic mechanical allodynia in the whisker pad skin after CFA injection into the lower lip.
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Neuroscience letters · Oct 2012
ReviewCellular and molecular approaches to motor neuron therapy in amyotrophic lateral sclerosis and spinal muscular atrophy.
Amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) are progressive fatal neurodegenerative diseases. They differ in their disease development but have in common a loss of motor neuron as they progress. Research is ongoing to further understand the origin of these diseases but this common thread of motor neuron loss has provided a target for the development of therapies for both ALS and SMA. It is the linked fields of gene and cell therapy that are providing some of the most interesting therapeutic possibilities.