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Positive Allosteric Modulation of TRPV1 as a Novel Analgesic Mechanism

Overview of attention for article published in Molecular Pain, January 2012
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • Among the highest-scoring outputs from this source (#23 of 519)
  • High Attention Score compared to outputs of the same age (89th percentile)
  • High Attention Score compared to outputs of the same age and source (91st percentile)

Mentioned by

blogs
1 blog
twitter
1 tweeter
patent
1 patent

Citations

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23 Dimensions

Readers on

mendeley
62 Mendeley
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Title
Positive Allosteric Modulation of TRPV1 as a Novel Analgesic Mechanism
Published in
Molecular Pain, January 2012
DOI 10.1186/1744-8069-8-70
Pubmed ID
Authors

Evan E Lebovitz, Jason M Keller, Hal Kominsky, Krisztian Kaszas, Dragan Maric, Michael J Iadarola

Abstract

The prevalence of long-term opiate use in treating chronic non-cancer pain is increasing, and prescription opioid abuse and dependence are a major public health concern. To explore alternatives to opioid-based analgesia, the present study investigates a novel allosteric pharmacological approach operating through the cation channel TRPV1. This channel is highly expressed in subpopulations of primary afferent unmyelinated C- and lightly-myelinated Aδ-fibers that detect low and high rates of noxious heating, respectively, and it is also activated by vanilloid agonists and low pH. Sufficient doses of exogenous vanilloid agonists, such as capsaicin or resiniferatoxin, can inactivate/deactivate primary afferent endings due to calcium overload, and we hypothesized that positive allosteric modulation of agonist-activated TRPV1 could produce a selective, temporary inactivation of nociceptive nerve terminals in vivo. We previously identified MRS1477, a 1,4-dihydropyridine that potentiates vanilloid and pH activation of TRPV1 in vitro, but displays no detectable intrinsic agonist activity of its own. To study the in vivo effects of MRS1477, we injected the hind paws of rats with a non-deactivating dose of capsaicin, MRS1477, or the combination. An infrared diode laser was used to stimulate TRPV1-expressing nerve terminals and the latency and intensity of paw withdrawal responses were recorded. qRT-PCR and immunohistochemistry were performed on dorsal root ganglia to examine changes in gene expression and the cellular specificity of such changes following treatment. Withdrawal responses of the capsaicin-only or MRS1477-only treated paws were not significantly different from the untreated, contralateral paws. However, rats treated with the combination of capsaicin and MRS1477 exhibited increased withdrawal latency and decreased response intensity consistent with agonist potentiation and inactivation or lesion of TRPV1-containing nerve terminals. The loss of nerve endings was manifested by an increase in levels of axotomy markers assessed by qRT-PCR and colocalization of ATF3 in TRPV1+ cells visualized via immunohistochemistry. The present observations suggest a novel, non-narcotic, selective, long-lasting TRPV1-based approach for analgesia that may be effective in acute, persistent, or chronic pain disorders.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 62 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 1 2%
Germany 1 2%
Unknown 60 97%

Demographic breakdown

Readers by professional status Count As %
Student > Master 12 19%
Researcher 8 13%
Student > Bachelor 8 13%
Student > Doctoral Student 6 10%
Other 5 8%
Other 12 19%
Unknown 11 18%
Readers by discipline Count As %
Agricultural and Biological Sciences 14 23%
Medicine and Dentistry 12 19%
Biochemistry, Genetics and Molecular Biology 7 11%
Psychology 4 6%
Neuroscience 4 6%
Other 10 16%
Unknown 11 18%

Attention Score in Context

This research output has an Altmetric Attention Score of 11. 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 20 February 2019.
All research outputs
#1,668,006
of 14,839,307 outputs
Outputs from Molecular Pain
#23
of 519 outputs
Outputs of similar age
#14,382
of 132,551 outputs
Outputs of similar age from Molecular Pain
#4
of 45 outputs
Altmetric has tracked 14,839,307 research outputs across all sources so far. Compared to these this one has done well and is in the 88th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 519 research outputs from this source. They receive a mean Attention Score of 3.5. This one has done particularly well, scoring higher than 95% of its peers.
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 132,551 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 89% of its contemporaries.
We're also able to compare this research output to 45 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 91% of its contemporaries.