Anja Armbruster, Elena Neumann, Valentin Kötter, Henning Hermanns, Robert Werdehausen, Volker Eulenburg
Abstract
Background: Chronic pain conditions are difficult to treat and the therapeutic outcome is frequently unsatisfactory. Changes in excitation/inhibition balance within the dorsal horn contribute to the establishment and persistence of chronic pain. Thus, facilitation of inhibitory neurotransmission is a promising approach to treat chronic pain pharmacologically. Glycine transporter 1 (GlyT1) plays an important role in regulating extracellular glycine concentrations. Aim of the present study therefore was to investigate whether the specific GlyT1 inhibitor bitopertin (RG1678; RO4917838) might constitute a novel treatment for chronic pain by facilitating glycinergic inhibition. Methods: Mechanical allodynia and thermal hyperalgesia were induced by chronic constriction injury of the sciatic nerve or carrageenan injections into the plantar surface of the hind paw in rodents. The effect of acute and long-term bitopertin application on the reaction threshold to mechanical and thermal stimuli was determined. General activity was determined in open field experiments. The glycine concentration in cerebrospinal fluid and blood was measured by HPLC. Results: Systemic application of bitopertin in chronic pain conditions lead to a significant increase of the reaction thresholds to mechanical and thermal stimuli in a time and dose-dependent manner. Long-term application of bitopertin effectuated stable beneficial effects over 4 weeks. Bitopertin did not alter reaction thresholds to stimuli in control animals and had no effect on general locomotor activity and anxiety but lead to an increased glycine concentration in cerebrospinal fluid. Conclusion: These findings suggest that inhibition of the GlyT1 by bitopertin represents a promising new approach for the treatment of chronic pain.
Pharmacology, Toxicology and Pharmaceutical Science
5
14%
Medicine and Dentistry
4
11%
Chemistry
3
9%
Biochemistry, Genetics and Molecular Biology
2
6%
Other
2
6%
Unknown
13
37%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 2. 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 17 September 2022.
All research outputs
#16,074,797
of 24,457,696 outputs
Outputs from Frontiers in Molecular Neuroscience
#1,861
of 3,195 outputs
Outputs of similar age
#266,987
of 452,628 outputs
Outputs of similar age from Frontiers in Molecular Neuroscience
#65
of 118 outputs
Altmetric has tracked 24,457,696 research outputs across all sources so far. This one is in the 32nd percentile – i.e., 32% of other outputs scored the same or lower than it.
So far Altmetric has tracked 3,195 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.1. This one is in the 36th percentile – i.e., 36% 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 452,628 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 38th percentile – i.e., 38% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 118 others from the same source and published within six weeks on either side of this one. This one is in the 37th percentile – i.e., 37% of its contemporaries scored the same or lower than it.
