Related Experiment Video

Updated: Jul 13, 2025

Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
11:48

Detection of Alternative Splicing During Epithelial-Mesenchymal Transition

Published on: October 9, 2014

13.0K

CWC22-Mediated Alternative Splicing of Spp1 Regulates Nociception in Inflammatory Pain

Yu Song1, Zhi-Yong Wang2, Jun Luo3

  • 1Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu Province 221004, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu Province 221004, China; Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province 221002, China.

Neuroscience
|October 14, 2023
PubMed

Insights

This study reveals that elevated CWC22 in the spinal cord drives inflammatory pain by altering Spp1 V4 splicing. Reducing CWC22 alleviates pain, suggesting it as a therapeutic target for chronic pain conditions.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Alternative splicing is implicated in pain mechanisms, but the specific factors and pathways involved are not fully understood.
  • Inflammatory pain models are crucial for investigating the molecular underpinnings of pain sensitization.

Purpose of the Study:

  • To elucidate the role and mechanism of splicing factor CWC22 in the development of inflammatory pain.
  • To identify specific splicing events regulated by CWC22 that contribute to nociception.

Main Methods:

  • Induction of inflammatory pain in mice using complete Freund's adjuvant (CFA).
  • Utilized lentivirus-mediated gene knockdown and overexpression of CWC22 in the spinal cord.
  • Performed behavioral tests for thermal hyperalgesia and mechanical allodynia.
  • Employed transcriptomic and genomic analyses to identify CWC22 targets.

Main Results:

  • CWC22 mRNA and protein levels were significantly increased in the spinal dorsal horn following CFA injection.
  • Knockdown of spinal CWC22 attenuated CFA-induced pain behaviors, while its upregulation induced pain in naive mice.
  • Transcriptome analysis identified Spp1 as a CWC22-regulated gene, with Spp1 variant 4 (Spp1 V4) specifically linked to nociceptive regulation.

Conclusions:

  • Spinal CWC22 plays a critical role in mediating inflammatory pain through the regulation of Spp1 V4 alternative splicing.
  • Targeting CWC22 or its downstream splicing events presents a potential therapeutic strategy for managing persistent inflammatory pain.
Keywords:
CWC22Spp1Spp1 V4alternative splicinginflammatory painnociception

More Related Videos

In Vivo SiRNA Transfection and Gene Knockdown in Spinal Cord via Rapid Noninvasive Lumbar Intrathecal Injections in Mice05:24

In Vivo SiRNA Transfection and Gene Knockdown in Spinal Cord via Rapid Noninvasive Lumbar Intrathecal Injections in Mice

Published on: March 22, 2014

46.7K
The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice07:09

The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice

Published on: July 16, 2014

48.2K

Related Concept Videos

Alternative RNA Splicing02:18

Alternative RNA Splicing

Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
21.2K
Nociception01:44

Nociception

Nociception—the ability to feel pain—is essential for an organism’s survival and overall well-being. Noxious stimuli such as piercing pain from a sharp object, heat from an open flame, or contact with corrosive chemicals are first detected by sensory receptors, called nociceptors, located on nerve endings. Nociceptors express ion channels that convert noxious stimuli into electrical signals. When these signals reach the brain via sensory neurons, they are perceived as pain.
27.9K
RNA Splicing01:32

RNA Splicing

Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
56.4K
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
7.3K
Major Somatic Sensory Pathways01:28

Major Somatic Sensory Pathways

Sensory impulses related to touch, pressure, vibration, and proprioception from various body parts, such as the limbs, trunk, neck, and posterior head, travel to the cerebral cortex through the posterior column-medial lemniscus pathway. The pathway’s name derives from the two white-matter tracts that convey the impulses: the spinal cord's posterior column and the brainstem's medial lemniscus. First-order sensory neurons extend their axons into the spinal cord, forming the...
997
Pain01:20

Pain

Pain serves as a critical warning signal that alerts the body to potential or actual harm. When mechanical pressure on the skin is intense, such as from a sharp pinch, the sensation transitions from touch to pain. Similarly, extreme temperatures, like a hot pot handle, convert the sensation of heat into pain. Pain can also result from overstimulation of other senses, such as blinding light, loud noise, or the intense heat from habañero peppers. This ability to sense pain is essential for...
487