Neuroscience
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Ankyrin-repeat transient receptor potential 1 (TRPA1) is a member of the transient receptor potential (TRP) channel family and it is found in sensory neurons. In the present study, we found that TRPA1 receptor activation with allyl isothiocyanate or cinnamaldehyde caused dose-dependent spontaneous nociception when injected into the mouse hind paw. Very similar results were obtained when stimulating transient receptor potential vanilloid 1 (TRPV1) receptors with capsaicin. ⋯ The selective NK(1) receptor antagonist N(2)-[(4R)-4-hydroxy-1-(1-methyl-1H-indol-3-yl) carbony-1-L-prolyl]-N-methyl-N-phenylmethyl-3-2-(2-naphtyl)-L-alaninamide (10 nmol/paw) reduced either capsaicin- or allyl isothiocyanate-induced nociception. Collectively, the present findings demonstrate that the TRPA1 agonist allyl isothiocyanate produces a consistent nociceptive response when injected into the mouse paw, an effect that seems to be mediated via activation of TRPA1 receptor and dependent on the capsaicin-sensitive fibers, release of histamine by mast cells and participation of tachykinins. Thus, the TRPA1 receptor has an apparently relevant role in nociceptive processes and the selective TRPA1 antagonist might possess a potential antinociceptive property.
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After recovery from acute muscle pain even minor subsequent muscle use can initiate recurrence of the same mechanical hyperalgesia months or years after the initial injury. We have recently developed a model of this chronic latent hyperalgesia in the rat. In this study, we have examined the possibility that interleukin-6 (IL-6), an inflammatory mediator produced during acute muscle inflammation, can mediate the production of this chronic latent hyperalgesic state in which subsequent exposure to inflammatory mediators produces a markedly prolonged mechanical hyperalgesia. ⋯ This ability of IL-6 to produce chronic latent hyperalgesia was prevented by intrathecal administration of antisense for gp130. Furthermore, gp130 antisense also prevented chronic latent hyperalgesia produced by i.m. injection of the inflammogen, carrageenan. These results identify a role for IL-6 in acute inflammatory muscle pain and as a potential target against which therapies might be directed to treat chronic muscle pain.
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Injuries to the cauda equina/conus medullaris portion of the spinal cord can result in motor, sensory, and autonomic dysfunction, and neuropathic pain. In rats, unilateral avulsion of the motor efferents from the lumbosacral spinal cord results in at-level allodynia, along with a corresponding glial and inflammatory response in the dorsal horn of the spinal cord segments immediately rostral to the lesion. Here, we investigated the fate of intramedullary primary sensory projections following a motor efferent lesion. ⋯ These results show for the first time that a lesion restricted to motor roots can induce the degeneration of intramedullary sensory afferents. Importantly, reimplantation of the lesioned motor roots ameliorated sensory axon degeneration. These data further support the therapeutic potential for reimplantation of avulsed ventral roots following trauma to the cauda equina/conus medullaris.
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Mutations in leucine-rich repeat kinase 2 (LRRK2) constitute the most common known cause of Parkinson's disease (PD), accounting for both familial and sporadic forms of the disease. We analyzed the tempo-spatial activity of leucine-rich repeat kinase 1 (LRRK1) and LRRK2 at the cellular level in human and rat tissues including development and aging. Lrrk2 mRNA is expressed in adult rat striatum, hippocampus, cerebral cortex, sensory and sympathetic ganglia, lung, spleen and kidney. ⋯ Transcription of both genes is also seen in the young human thymus and LRRK2 is active in tubular parts of the adult human kidney. Our findings suggest that the two paralogous genes have partly complementary expression patterns in the brain, as well as in certain peripheral organs including lymphatic tissues. While the strong presence of Lrrk2 message in striatum is intriguing in relation to PD, the many other neuronal and non-neuronal sites of Lrrk2 activity also needs to be taken into account in deciphering possible pathogenic pathways.
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Deep brain stimulation (DBS) was applied in the internal segment of the globus pallidus (GPi) to treat dystonia in 10 patients. One year after surgery the Burke-Fahn-Marsden movement scores were significantly lower than preoperative values (P=0.01). Two years after surgery the mean decrease reached 65% (P=0.001) with no motor symptoms worsening. ⋯ We conclude that DBS in the GPi is a reliable surgical technique for dystonia. GPi cells discharge with distinct electrophysiological characteristics that may explain some of the symptoms in dystonia. EMG recording in the operating room helps to determine which DBS contacts produce the best benefit.