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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Cation chloride co-transporters are important determinants for the efficacy of inhibitory neurotransmission in the spinal cord and alterations in their expression levels contribute to allodynia and hyperalgesia associated with neuropathy. However, it remains unknown whether these co-transporters contribute to chronic inflammatory pain. We investigated the expression of potassium-chloride co-transporter 2 (KCC2) and sodium-potassium-chloride co-transporter 1 (NKCC1) in the rat spinal cord after peripheral inflammation induced by complete Freund's adjuvant (CFA) injection. ⋯ Moreover, intrathecal injection of KCC2 antisense oligodeoxynucleotides into naïve rats reduced KCC2 expression in the spinal cord, leading to behavioral hypersensitivity similar to the hyperalgesia induced by peripheral inflammation. Taken together, these results indicate that peripheral inflammation induces downregulation of KCC2 in the dorsal horn of the spinal cord, which may in turn facilitate the development and/or maintenance of chronic inflammatory pain. The data also support the notion that disinhibition in the spinal cord is a general feature of inflammatory and neuropathic pain conditions, and suggest new therapeutic intervention.
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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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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.
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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.