General pain - page 3 Scientific Publications

Latest publication 01/01/2025

AAV-mediated overexpression of Prdm12 in knee-innervating afferents reduces infl

Inflammatory joint pain features in numerous musculoskeletal disorders that affect millions globally. The Prdm12 gene encodes a conserved zinc...

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    [title] => AAV-mediated overexpression of Prdm12 in knee-innervating afferents reduces infl
    [paragraph] => AAV-mediated overexpression of Prdm12 in knee-innervating afferents reduces inflammatory joint pain and neuronal hyperexcitability in mice
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Authors
Maya Dannawi, Luke A Pattison, Alex Cloake, Eric Bellefroid, Ewan St. John Smith


Lab

Journal
bioRxiv

Abstract

Inflammatory joint pain features in numerous musculoskeletal disorders that affect millions globally. The Prdm12 gene encodes a conserved zinc finger transcriptional regulator expressed selectively in the nervous system. In humans, PRDM12 mutations can cause congenital insensitivity to pain (CIP) or midface toddler excoriation syndrome (MiTES). Prdm12 is prominently expressed in developing somatosensory ganglia, where it plays a crucial role in nociceptive neuron development, its expression being maintained in mature C-LTMRs (C-low threshold mechanoreceptors) and nociceptive neurons. Despite enhanced understanding of Prdm129s role in neuronal excitability and pain behavior, the impact of Prdm12 overexpression in mature nociceptive neurons has not been explored. Here, we conducted intravenous injection of AAV-PHP.S viral vectors encoding Prdm12-GFP (Prdm12-AAV) or GFP alone (Control-AAV), observing no overt changes in mouse behavior. When examining the properties of Prdm12 overexpressing sensory neurons in vitro, we observed an increase in rheobase alongside decreased neuronal responses to capsaicin and ATP, indicating a downregulation of TRPV1 and P2X ion channels activity, respectively. We next conducted intraarticular administration of viral constructs in female mice to determine how Prdm12 overexpression in knee-innervating sensory neurons alters their excitability and influences inflammatory joint pain induced by intraarticular administration of complete Freund9s adjuvant (CFA). Prdm12 overexpression in knee-innervating neurons decreased inflammation-induced changes in digging and weight bearing, prevented inflammation-induced neuronal hyperexcitability, and decreased macroscopic voltage-gated ion channel conductance. Our findings illustrate that Prdm12 overexpression strongly modulates neuronal excitability in adult animals, highlighting its importance in pain perception and its potential as an analgesic target.

Keywords/Topics
Prdm12; Pain; Behavior; Electrophysiology; Transcription regulation; Gene Therapy

BIOSEB Instruments Used:
Dynamic Weight Bearing 2.0 (BIO-DWB-DUAL)

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The advanced version of our Dynamic Weight Bearing Test for rodents (rats and mice) allows for faster paw identification, based on a video solution taking advantage of the most advanced algorithms of morphologic analysis, weight distribution and postural changes in dynamic conditions. An efficient and advanced alternative to traditional incapacitance tests (i.e. the paw pressure test or the force plate test) for assessing pain sensitivity in your research on analgesia, hyperalgesia and nociception involving rats and mice, including work on osteoarthritis, bone cancer, analgesic substances, Parkinson disease, allodynia...

Instrument for ratsInstrument for mice

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