Neuroscience letters
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Neuroscience letters · Mar 2008
Repeated administration of mirtazapine inhibits development of hyperalgesia/allodynia and activation of NF-kappaB in a rat model of neuropathic pain.
Antidepressants have been widely used to treat neuropathic pain for many years. However, the mechanisms of their analgesic actions are little known and remain controvertible. Recent studies indicate that cytokines in central nervous system (CNS) play a critical role in the pathological states of pain. ⋯ We found that mirtazapine (20 and 30 mg/kg) can markedly attenuate mechanical and thermal hyperalgesia produced by nerve transection, most significantly on the 14th day. The elevated TNFalpha, IL-1beta and NF-kappaB in brain were accordingly reduced, while the expression of increased IL-10 were even stimulated after repeated mirtazapine administration. Our data could conclude that mirtazapine suppressed neuropathic pain partially through inhibiting cerebral proinflammatory cytokines production and NF-kappaB activation in CNS.
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Neuroscience letters · Feb 2008
A transient receptor potential vanilloid 4 contributes to mechanical allodynia following chronic compression of dorsal root ganglion in rats.
The aim of the present study was to investigate the role of transient receptor potential vanilloid 4 (TRPV4) in mediating mechanical allodynia in rodent models of chronic compression of the dorsal root ganglion (CCD). First, the levels of TRPV4 mRNA and protein expression in the dorsal root ganglion (DRG) were assessed using real-time RT-PCR and Western blotting analysis respectively at 7, 14, and 28 days post-CCD. Then, the effects of spinal administration of TRPV4 antisense oligodeoxynucleotide (ODN) and mismatch ODN on CCD-induced mechanical allodynia were evaluated. ⋯ The percentage of DRG neurons responsive to hypotonic solution and 4alpha-PDD and the fluorescence ratio of calcium response were also enhanced significantly in both the CCD group and the mismatch ODN group. These increased responses were significantly inhibited by TRPV4 antisense ODN. In conclusion, TRPV4 plays a crucial role in CCD-induced mechanical allodynia.
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Neuroscience letters · Feb 2008
A novel human foamy virus mediated gene transfer of GAD67 reduces neuropathic pain following spinal cord injury.
Neuropathic pain is a long-lasting clinical problem that is often refractory to medical management. Gene transfer of specific genes for therapeutic benefit offers a novel approach to the treatment of neuropathic pain. In this study, we tested whether the transfer of the glutamic acid decarboxylase (GAD) gene to dorsal root ganglion (DRG) cells would attenuate below-injury level central neuropathic pain after spinal cord injury (SCI) by using a novel human foamy virus (HFV) vector to achieve release of gamma-aminobutyric acid (GABA). ⋯ The antiallodynic effect lasted 6 weeks and was reestablished by reinoculation. We also found that subcutaneous inoculation of rdvGAD67 resulted in enhanced production of GAD and tonical GABA release from transduced DRG neurons. These results suggest that HFV-mediated gene transfer to DRG could be employed to treat below-injury level central neuropathic pain after incomplete SCI.
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Neuroscience letters · Feb 2008
Mitochondrial transcription factor A (TFAM) gene variation in Parkinson's disease.
Mitochondrial function is necessary to supply the energy required for cell metabolism. Mutations/polymorphisms in mitochondrial DNA (mtDNA) have been implicated in Parkinson's disease (PD). The mitochondrial transcription factor A (TFAM) controls the transcription of mtDNA and regulates the mtDNA-copy number, thus being important for maintaining ATP production. ⋯ We found five common polymorphisms, and only one was a missense change (S12T in exon 1). Genotype and allele frequencies did not differ between patients and healthy controls (n=225) for the five polymorphisms. Our work suggests that TFAM-variants did not contribute to the risk of developing PD.
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Neuroscience letters · Feb 2008
Environmental enrichment-mediated functional improvement after experimental traumatic brain injury is contingent on task-specific neurobehavioral experience.
Environmental enrichment (EE) is superior to standard (STD) housing in promoting functional recovery after traumatic brain injury (TBI). However, whether the EE-mediated benefits after TBI are dependent on exposure to enrichment during neurobehavioral training has not been elucidated. To address this issue, isoflurane-anesthetized adult male rats received either a cortical impact or sham injury and were then randomly assigned to early EE, delayed EE, continuous EE or no EE (i.e., STD conditions). ⋯ Beam-walking was facilitated in the TBI groups that received either early or continuous EE versus those receiving delayed or no EE. Cognitive training was enhanced in the TBI groups that received continuous or delayed EE versus the early EE or no EE groups. These data suggest that EE-mediated functional improvement after TBI is contingent on task-specific neurobehavioral experience.