Search results for " Spinal"
showing 10 items of 188 documents
Effects of Anandamide and Noxious Heat on Intracellular Calcium Concentration in Nociceptive DRG Neurons of Rats
2007
As an endogenous agonist at the cannabinoid receptor CB1 and the capsaicin-receptor TRPV1, anandamide may exert both anti- and pronociceptive actions. Therefore we studied the effects of anandamide and other activators of both receptors on changes in free cytosolic calcium ([Ca2+]i) in acutely dissociated small dorsal root ganglion neurons (diameter: ≤30 μm). Anandamide (10 μM) increased [Ca2+]iin 76% of the neurons. The EC50was 7.41 μM, the Hill slope was 2.15 ± 0.43 (mean ± SE). This increase was blocked by the competitive TRPV1-antagonist capsazepine (10 μM) and in Ca2+-free extracellular solution. Neither exclusion of voltage-gated sodium channels nor additional blockade of voltage-gate…
Coexpression of heat-evoked and capsaicin-evoked inward currents in acutely dissociated rat dorsal root ganglion neurons.
1997
Noxious heat is able to activate heat-sensitive nociceptors in the skin very rapidly, but little is known about the mechanisms by which heat is transduced. We used the whole-cell patch-clamp technique to study the effects of noxious heat and capsaicin on freshly dissociated rat dorsal root ganglion neurons in vitro. Using temperatures between 41 degrees C and 53 degrees C, 8 of 19 small neurons (phior = 30 microm) exhibited a heat-evoked inward current. All heat-sensitive neurons tested were also capsaicin-sensitive. Moreover, the heat response tended to be enhanced after capsaicin (360 +/- 150 pA versus 125 +/- 45 pA, P0.1, n = 7). Two of five heat-insensitive neurons were excited by capsa…
Post-translational modifications in the survival motor neuron protein
2004
Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by a progressive loss of the spinal motoneurons. The SMA-determining gene has been termed survival motor neuron (SMN) and is deleted or mutated in over 98% of patients. The encoded gene product is a protein expressed as different isoforms. In particular, we showed that the rat SMN cDNA produces two isoforms with Mr of 32 and 35 kDa, both localized in nuclear coiled bodies, but the 32 kDa form is also cytoplasmic, whereas the 35 kDa form is also microsomal. To determine the molecular relationship between these two isoforms and potential post-translational modifications, we performed transfection experiments with a …
Inactivation and tachyphylaxis of heat-evoked inward currents in nociceptive primary sensory neurones of rats.
2000
In contrast to other sensory modalities, pain does not decrease when a noxious stimulus is applied at constant intensity (Greene & Hardy, 1962). From this lack of adaptation on the perceptive level it has traditionally been implied that primary nociceptive afferents also do not adapt upon constant stimulation. This is in contrast to the results of recordings from these afferents, which exhibit pronounced adaptation for physical as well as chemical stimuli (Meyer et al. 1994). Peripheral adaptation of nociceptive nerve endings is compensated by central summation (Mendell & Wall, 1965; Price et al. 1977); this slow summation process of small fibre input to the dorsal horn of the spinal cord i…
Active acetylcholine receptors prevent the atrophy of skeletal muscles and favor reinnervation
2020
Denervation of skeletal muscles induces severe muscle atrophy, which is preceded by cellular alterations such as increased plasma membrane permeability, reduced resting membrane potential and accelerated protein catabolism. The factors that induce these changes remain unknown. Conversely, functional recovery following denervation depends on successful reinnervation. Here, we show that activation of nicotinic acetylcholine receptors (nAChRs) by quantal release of acetylcholine (ACh) from motoneurons is sufficient to prevent changes induced by denervation. Using in vitro assays, ACh and non-hydrolysable ACh analogs repressed the expression of connexin43 and connexin45 hemichannels, which prom…
SETD7 mediates spinal microgliosis and neuropathic pain in a rat model of peripheral nerve injury
2019
Abstract Gene transcription regulation is critical for the development of spinal microgliosis and neuropathic pain after peripheral nerve injury. Using a model of chronic constriction injury (CCI) of the sciatic nerve, this study characterized the role of SET domain containing lysine methyltransferase 7 (SETD7) which monomethylates histone H3 lysine 4 (H3K4me1), a marker for active gene transcription. SETD7 protein expression in the spinal dorsal horn ipsilateral to nerve lesion was increased from one day to 14 days after CCI, concomitantly with the expression of inflammatory genes, Ccl2, Il-6 and Il-1β. The CCI-induced SETD7 expression was predominantly localized to microglia, as demonstra…
Improve hip fracture outcome in the elderly patient (iHOPE) : A study protocol for a pragmatic, multicentre randomised controlled trial to test the e…
2018
IntroductionHip fracture surgery is associated with high in-hospital and 30-day mortality rates and serious adverse patient outcomes. Evidence from randomised controlled trials regarding effectiveness of spinal versus general anaesthesia on patient-centred outcomes after hip fracture surgery is sparse.Methods and analysisThe iHOPE study is a pragmatic national, multicentre, randomised controlled, open-label clinical trial with a two-arm parallel group design. In total, 1032 patients with hip fracture (>65 years) will be randomised in an intended 1:1 allocation ratio to receive spinal anaesthesia (n=516) or general anaesthesia (n=516). Outcome assessment will occur in a blinded manner aft…
Mutations in the Matrin 3 gene cause familial amyotrophic lateral sclerosis.
2013
MATR3 is an RNA- and DNA-binding protein that interacts with TDP-43, a disease protein linked to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Using exome sequencing, we identified mutations in MATR3 in ALS kindreds. We also observed MATR3 pathology in ALS-affected spinal cords with and without MATR3 mutations. Our data provide more evidence supporting the role of aberrant RNA processing in motor neuron degeneration. © 2014 Nature America, Inc. All rights reserved.
Inhibition of rapid heat responses in nociceptive primary sensory neurons of rats by vanilloid receptor antagonists.
1999
Recent studies demonstrated that heat-sensitive nociceptive primary sensory neurons respond to the vanilloid receptor (VR) agonist capsaicin, and the first cloned VR is a heat-sensitive ion channel. Therefore we studied to what extent heat-evoked currents in nociceptive dorsal root ganglion (DRG) neurons can be attributed to the activation of native vanilloid receptors. Heat-evoked currents were investigated in 89 neurons acutely dissociated from adult rat DRGs as models for their own terminals using the whole cell patch-clamp technique. Locally applied heated extracellular solution (effective temperature ∼53°C) rapidly activated reversible and reproducible inward currents in 80% (62/80) o…
Spinopelvic changes based on the simplified SRS-Schwab adult spinal deformity classification: relationships with disability and health-related qualit…
2018
Study design Cross-sectional, observational study. Objective To study the occurrence of sagittal malalignment, the adaptability of a simplified sagittal modifiers grading of the Scoliosis Research Society (SRS)-Schwab adult spinal deformity (ASD) classification, and the deformity-specific SRS questionnaire version 30 (SRS-30) in an unselected adult cohort with symptomatic degenerative spinal disorders. Summary of background data The sagittal modifiers of the SRS-Schwab ASD classification correlate with health-related quality of life (HRQoL) measures in patients with ASD. The deformities and disabilities caused by sagittal malalignment in patients with common degenerative spinal disorders of…