Dataset Information

Initial evaluation of nighttime restlessness in a naturally occurring canine model of osteoarthritis pain.

ABSTRACT: Chronic pain due to osteoarthritis (OA) can lead to significant disruption of sleep and increased restlessness. Our objective was to assess whether naturally occurring canine OA is associated with nighttime restlessness and so has potential as a model of OA-associated sleep disturbance. The study was designed as a two-part prospective masked, placebo-controlled study using client-owned dogs (Part A n = 60; Part B n = 19). Inclusion criteria consisted of OA-associated joint pain and mobility impairment. The primary outcome measure for both parts was nighttime accelerometry. In Part B, quality of sleep was assessed using a clinical metrology instrument (Sleep and Night Time Restlessness Evaluation Score, SNoRE). Part A included dogs receiving two weeks of non-steroidal anti-inflammatory drug (NSAID) preceded with two weeks of no treatment. Part B was a crossover study, with NSAID/placebo administered for two weeks followed by a washout period of one week and another two weeks of NSAID/placebo. Repeated measures analysis of variance was used to assess differences between baseline and treatment. There were no significant changes in accelerometry-measured nighttime activity as a result of NSAID administration. SNoRE measures indicated significant improvements in aspects of the quality of nighttime sleep that did not involve obvious movement. These results reflect the few similar studies in human OA patients. Although accelerometry does not appear to be useful, this model has potential to model the human pain-related nighttime sleep disturbance, and other outcome measures should be explored in this model.

SUBMITTER: Knazovicky D

PROVIDER: S-EPMC4340376 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Congenital stationary night blindness (CSNB) is a non-progressive, clinically and genetically heterogeneous disease of impaired night vision. We report a naturally-occurring, stationary, autosomal recessive phenotype in beagle dogs with normal daylight vision but absent night vision. Affected dogs had normal retinas on clinical examination, but showed no detectable rod responses. They had "negative-type" mixed rod and cone responses in full-field ERGs. Their photopic long-flash ERGs had normal OFF-responses associated with severely reduced ON-responses. The phenotype is similar to the Schubert-Bornschein form of complete CSNB in humans. Homozygosity mapping ruled out most known CSNB candidates as well as CACNA2D4 and GNB3. Three remaining genes were excluded based on sequencing the open reading frame and intron-exon boundaries (RHO, NYX), causal to a different form of CSNB (RHO) or X-chromosome (NYX, CACNA1F) location. Among the genes expressed in the photoreceptors and their synaptic terminals, and mGluR6 cascade and modulators, reduced expression of GNAT1, CACNA2D4 and NYX was observed by qRT-PCR in both carrier (n = 2) and affected (n = 2) retinas whereas CACNA1F was down-regulated only in the affecteds. Retinal morphology revealed normal cellular layers and structure, and electron microscopy showed normal rod spherules and synaptic ribbons. No difference from normal was observed by immunohistochemistry (IHC) for antibodies labeling rods, cones and their presynaptic terminals. None of the retinas showed any sign of stress. Selected proteins of mGluR6 cascade and its modulators were examined by IHC and showed that PKC? weakly labeled the rod bipolar somata in the affected, but intensely labeled axonal terminals that appeared thickened and irregular. Dendritic terminals of ON-bipolar cells showed increased Go? labeling. Both PKC? and Go? labeled the more prominent bipolar dendrites that extended into the OPL in affected but not normal retinas. Interestingly, RGS11 showed no labeling in the affected retina. Our results indicate involvement of a yet unknown gene in this canine model of complete CSNB.

Project description:Gliogenesis under pathophysiological conditions is of particular clinical relevance since it may provide evidence for regeneration promoting cells recruitable for therapeutic purposes. There is evidence that neurotrophin receptor p75 (p75NTR)-expressing cells emerge in the lesioned CNS. However, the phenotype and identity of these cells, and signals triggering their in situ generation under normal conditions and certain pathological situations has remained enigmatic. In the present study, we used a spontaneous, idiopathic and inflammatory CNS condition in dogs with prominent lympho-histiocytic infiltration as a model to study the phenotype of Schwann cells and their relation to Schwann cell remyelination within the CNS. Furthermore, the phenotype of p75NTR-expressing cells within the injured CNS was compared to their counter-part in control sciatic nerve and after peripheral nerve injury. In addition, organotypic slice cultures were used to further elucidate the origin of p75NTR-positive cells. In cerebral and cerebellar white and grey matter lesions as well as in the brain stem, p75NTR-positive cells co-expressed the transcription factor Sox2, but not GAP-43, GFAP, Egr2/Krox20, periaxin and PDGFR-α. Interestingly, and contrary to the findings in control sciatic nerves, p75NTR-expressing cells only co-localized with Sox2 in degenerative neuropathy, thus suggesting that such cells might represent dedifferentiated Schwann cells both in the injured CNS and PNS. Moreover, effective Schwann cell remyelination represented by periaxin- and P0-positive mature myelinating Schwann cells, was strikingly associated with the presence of p75NTR/Sox2-expressing Schwann cells. Intriguingly, the emergence of dedifferentiated Schwann cells was not affected by astrocytes, and a macrophage-dominated inflammatory response provided an adequate environment for Schwann cells plasticity within the injured CNS. Furthermore, axonal damage was reduced in brain stem areas with p75NTR/Sox2-positive cells. This study provides novel insights into the involvement of Schwann cells in CNS remyelination under natural occurring CNS inflammation. Targeting p75NTR/Sox2-expressing Schwann cells to enhance their differentiation into competent remyelinating cells appears to be a promising therapeutic approach for inflammatory/demyelinating CNS diseases.

Dataset Information

Initial evaluation of nighttime restlessness in a naturally occurring canine model of osteoarthritis pain.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets