Search results for "dorsal root ganglion"
showing 10 items of 19 documents
Sensory neuropathy in progressive motor neuronopathy(pmn)mice is associated with defects in microtubule polymerization and axonal transport
2016
Motor neuron diseases such as amyotrophic lateral sclerosis (ALS) are now recognized as multi-system disorders also involving various non-motor neuronal cell types. The precise extent and mechanistic basis of non-motor neuron damage in human ALS and ALS animal models remain however unclear. To address this, we here studied progressive motor neuronopathy (pmn) mice carrying a missense loss-of-function mutation in tubulin binding cofactor E (TBCE). These mice manifest a particularly aggressive form of motor axon dying back and display a microtubule loss, similar to that induced by human ALS-linked TUBA4A mutations. Using whole nerve confocal imaging of pmn × thy1.2-YFP16 fluorescent reporter …
Inward currents in primary nociceptive neurons of the rat and pain sensations in humans elicited by infrared diode laser pulses
2002
Radiant heat is often used to study nociception in vivo. We now used infrared radiation generated by a diode laser stimulator (wavelength 980 nm) to investigate transduction mechanisms for noxious heat stimuli in acutely dissociated dorsal root ganglion (DRG) neurons of rats in vitro. The laser stimulator offered the unique opportunity to test whether the same stimuli also elicit pain sensations in humans. A specific heat-induced current (I(heat)) was elicited in six of 13 small DRG neurons (diameteror =30 microm) tested in the whole-cell configuration of the patch-clamp mode. Current responses in the seven heat-insensitive neurons were within the range explainable by the temperature depend…
Co-expression of the voltage-gated potassium channel Kv1.4 with transient receptor potential channels (TRPV1 and TRPV2) and the cannabinoid receptor …
2006
Potassium channels contribute to basic neuronal excitability and modulation. Here, we examined expression patterns of the voltage-gated potassium channel Kv1.4, the nociceptive transduction channels TRPV1 and TRPV2 as well as the putative anti-nociceptive cannabinoid receptor CB1 by immunofluorescence double-labelings in sections of rat dorsal root ganglia (DRGs). Kv1.4, TRPV1 and CB1 were each detected in about one third of neurons (35.7+/-0.5%, 29.4+/-1.1% and 36.4+/-0.5%, respectively, mean diameter 19.1+/-0.3 microm). TRPV2 was present in 4.4+/-0.4% of all neurons that were significantly larger in diameter (27.4+/-0.7 microm; P < 0.001). Antibody double-labeling revealed that the majori…
Histone post-translational modifications as potential therapeutic targets for pain management
2021
Effective pharmacological management of pain associated with tissue pathology is an unmet medical need. Transcriptional modifications in nociceptive pathways are pivotal for the development and the maintenance of pain associated with tissue damage. Accumulating evidence has shown the importance of the epigenetic control of transcription in nociceptive pathways via histone post-translational modifications (PTMs). Hence, histone PTMs could be targets for novel effective analgesics. Here, we discuss the current understanding of histone PTMs in the modulation of gene expression affecting nociception and pain phenotypes following tissue injury. We also provide a critical view of the translationa…
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…
DNA Methylation and Non-Coding RNAs during Tissue-Injury Associated Pain.
2022
While about half of the population experience persistent pain associated with tissue damages during their lifetime, current symptom-based approaches often fail to reduce such pain to a satisfactory level. To provide better patient care, mechanism-based analgesic approaches must be developed, which necessitates a comprehensive understanding of the nociceptive mechanism leading to tissue injury-associated persistent pain. Epigenetic events leading the altered transcription in the nervous system are pivotal in the maintenance of pain in tissue injury. However, the mechanisms through which those events contribute to the persistence of pain are not fully understood. This review provides a summar…
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…
Differential localization of neuronal nitric oxide synthase immunoreactivity and NADPH-diaphorase activity in the cat spinal cord.
1994
The distributions of neuronal nitric oxide synthase immunoreactivity (NOS-IR) and NADPH-diaphorase (NADPH-d) activity were compared in the cat spinal cord. NOS-IR in neurons around the central canal, in superficial laminae (I and II) of the dorsal horn, in the dorsal commissure, and in fibers in the superficial dorsal horn was observed at all levels of the spinal cord. In these regions, NOS-IR paralleled NADPH-d activity. The sympathetic autonomic nucleus in the rostral lumbar and thoracic segments exhibited prominent NOS-IR and NADPH-d activity, whereas the parasympathetic nucleus in the sacral segments did not exhibit NOS-IR or NADPH-d activity. Within the region of the sympathetic autono…
Acetylsalicylic acid reduces heat responses in rat nociceptive primary sensory neurons – evidence for a new mechanism of action
2002
Acetylsalicylic acid (ASA) is thought to exert its peripheral analgesic effects via inhibition of cyclooxygenase. We now studied the effects of ASA on heat responses in primary nociceptive neurons by whole-cell patch-clamp and calcium microfluorimetry experiments. Heat-evoked inward currents in acutely dissociated rat dorsal root ganglion neurons were significantly reduced by ASA in a dose-dependent and reversible manner (IC(50) 375 nM, Hill slope -2.2, maximum effect 55%). Heat-evoked calcium transients (measured with FURA-2) were reversibly reduced by 53+/-14% (P0.05) by co-application of 1 microM ASA. The low IC(50) value, the rapid occurrence, and the reversibility of the observed effec…
Generalised sensory system abnormalities in amyotrophic lateral sclerosis: a European multicentre study.
2007
International audience; BACKGROUND: Amyotrophic lateral sclerosis (ALS) is defined as a disease of the motor neurones, although several studies indicate involvement of the sensory nervous system. AIM: To evaluate the sensory nerve conduction studies (NCS) in 88 patients with ALS as part of a European multicentre study. METHODS: Seven European clinical neurophysiologists examined consecutive series of ALS patients. The examinations were peer reviewed, and the diagnosis of ALS was confirmed clinically. RESULTS: 20 (22.7%) patients with ALS had sensory NCS abnormalities in at least one nerve. Of those, 11 (12.5% of all patients) obtained an additional peer review diagnosis of electrophysiologi…