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Antinociceptive effects of lacosamide on spinal neuronal and behavioural measures of pain in a rat model of osteoarthritis

Overview of attention for article published in Arthritis Research & Therapy, December 2014
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Title
Antinociceptive effects of lacosamide on spinal neuronal and behavioural measures of pain in a rat model of osteoarthritis
Published in
Arthritis Research & Therapy, December 2014
DOI 10.1186/s13075-014-0509-x
Pubmed ID
Authors

Wahida Rahman, Anthony H Dickenson

Abstract

IntroductionAlterations in voltage gated sodium channel (VGSC) function have been linked to chronic pain and are good targets for analgesics. Lacosamide (LCM) is a novel anticonvulsant that enhances the slow inactivation state of VGSCs. This conformational state can be induced by repeated neuronal firing and/or under conditions of sustained membrane depolarisation; as is expected for hyperexcitable neurones in pathological conditions such as epilepsy and neuropathy, and probably osteoarthritis (OA). This study, therefore, examined the antinociceptive effect of LCM on spinal neuronal and behavioural measures of pain, in vivo, in a rat OA model.MethodsOA was induced in Sprague Dawley rats by intra-articular injection of 2mg monosodium iodoacetate (MIA). Shams were injected with saline. Behavioural responses to mechanical and cooling stimulation of the ipsilateral hind paw and hind-limb weight bearing were recorded. In vivo electrophysiology was performed in anaesthetised MIA or sham rats, recording the effects of spinal or systemic administration of LCM on the evoked responses of dorsal horn neurones to electrical, mechanical (brush, von Frey (vF) 2-60g) and heat (40-50°C) stimulation of the peripheral receptive field. The effect of systemic LCM on nociceptive behaviours was assessed.ResultsBehavioural hypersensitivity, ipsilateral to knee injury, was seen as a reduced paw withdrawal threshold to mechanical stimulation, an increase in paw withdrawal frequency to cooling stimulation and hind-limb weight bearing asymmetry in MIA rats only. Spinal and systemic administration of LCM produced significant reductions of the electrical Aß- and C-fiber evoked neuronal responses and the mechanical and thermal evoked neuronal responses in the MIA group only. Systemic administration of LCM significantly reversed the behavioural hypersensitive responses to mechanical and cooling stimulation of the ipsilateral hind paw, but hind limb weight bearing asymmetry was not corrected.ConclusionsOur in vivo electrophysiological results show that the inhibitory effects of LCM were MIA dependent. This suggests that if used in OA patients, LCM may allow physiological transmission yet suppress secondary hyperlagesia and allodynia. The inhibitory effect on spinal neuronal firing aligned with analgesic efficacy on nociceptive behaviours and suggests that LCM may still prove worthwhile for OA pain treatment and merits further clinical investigation.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 33 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 33 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 6 18%
Student > Doctoral Student 5 15%
Other 4 12%
Researcher 4 12%
Student > Ph. D. Student 4 12%
Other 5 15%
Unknown 5 15%
Readers by discipline Count As %
Medicine and Dentistry 12 36%
Neuroscience 6 18%
Agricultural and Biological Sciences 4 12%
Engineering 2 6%
Economics, Econometrics and Finance 1 3%
Other 3 9%
Unknown 5 15%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 January 2015.
All research outputs
#3,076,099
of 4,729,227 outputs
Outputs from Arthritis Research & Therapy
#874
of 1,157 outputs
Outputs of similar age
#100,028
of 157,400 outputs
Outputs of similar age from Arthritis Research & Therapy
#41
of 52 outputs
Altmetric has tracked 4,729,227 research outputs across all sources so far. This one is in the 31st percentile – i.e., 31% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,157 research outputs from this source. They receive a mean Attention Score of 4.1. This one is in the 21st percentile – i.e., 21% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 157,400 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 32nd percentile – i.e., 32% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 52 others from the same source and published within six weeks on either side of this one. This one is in the 15th percentile – i.e., 15% of its contemporaries scored the same or lower than it.