SIRT1 Facilitates Beclin-1 Nuclear Translocation to Mitigate Nociceptive Hypersensitivity in Rats with Bone Cancer

Qiuli He1, Wenjie Li2, Cuie Deng3

  • 1Department of Anesthesiology and Pain Research Center, Jiaxing University Affiliated Hospital, The First Hospital of Jiaxing, Jiaxing, Zhejiang Province, China.

Pain Physician
|February 2, 2026
PubMed
Abstract

Insights

Sirtuin 1 (SIRT1) activation in rats with bone cancer pain (BCP) may reduce hypersensitivity by promoting autophagy. This study reveals a novel SIRT1 mechanism in BCP pain, offering therapeutic potential.

Area of Science:

  • Neuroscience
  • Oncology
  • Molecular Biology

Background:

  • Bone cancer pain (BCP) etiology is complex, with limited effective treatments.
  • Sirtuin 1 (SIRT1) is implicated in BCP pathogenesis, potentially modulating autophagy and pain sensitization.
  • The precise mechanisms underlying BCP remain incompletely understood.

Purpose of the Study:

  • To investigate the role of SIRT1 in autophagy activation.
  • To determine SIRT1's impact on nociceptive hypersensitivity in a rat BCP model.

Main Methods:

  • A rat model of BCP was established using Walker 256 breast cancer cells injected into the tibia.
  • Mechanical pain sensitivity was assessed using an Electronic von Frey Anesthesiometer.
  • Western blot and immunofluorescence assays analyzed SIRT1, beclin-1, LC3II/LC3I ratio, and P62 expression.

Main Results:

  • BCP rats exhibited reduced SIRT1 and increased beclin-1, LC3II/LC3I ratio, and P62 expression in spinal cord dorsal horns.
  • SIRT1 agonist treatment in BCP rats delayed SIRT1 downregulation, decreased beclin-1 acetylation, and promoted beclin-1 nuclear translocation.
  • SIRT1 activation reduced the LC3II/LC3I ratio and P62 levels, suggesting restored autophagic flux and ameliorated nociceptive hypersensitivity.

Conclusions:

  • SIRT1 activation may alleviate BCP-induced nociceptive hypersensitivity via enhanced autophagy and beclin-1 nuclear translocation.
  • This study identifies a novel SIRT1-mediated mechanism in BCP pain.
  • Findings suggest potential therapeutic strategies targeting SIRT1 for BCP management.

Related Concept Videos

Hypersensitivities01:30

Hypersensitivities

Hypersensitivity, also known as a hypersensitivity reaction or allergic reaction, is a condition where the body's immune system reacts abnormally to a foreign substance. Such substances, that cause hypersensitivity are referred to as an allergen, could be something typically harmless to most people, like pollen or certain foods.
Types of Hypersensitivities
Hypersensitivity reactions are categorized into four types: Type 1, Type 2, Type 3, and Type 4. Each type has a distinct mechanism...
7.5K
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.
33.3K
Restorative Care01:19

Restorative Care

Restorative care is provided once a patient has been discharged from a healthcare facility and requires additional services. The additional services include home care, rehabilitation programs, and extended care. Restorative care centers help the patient regain their previous level of functioning or acquire a new level of functioning due to the incapacitating effects of a disease or a disability. It aims to assist patients in enhancing their quality of life by encouraging independence,...
2.4K
Facilitated Transport01:19

Facilitated Transport

The chemical and physical properties of plasma membranes cause them to be selectively permeable. Since plasma membranes have both hydrophobic and hydrophilic regions, substances need to be able to transverse both regions. The hydrophobic area of membranes repels substances such as charged ions. Therefore, such substances need special membrane proteins to cross a membrane successfully. In  facilitated transport, also known as facilitated diffusion, molecules and ions travel across a...
148.1K
Social Facilitation01:04

Social Facilitation

Not all intergroup interactions lead to negative outcomes. Sometimes, being in a group situation can improve performance. Social facilitation occurs when an individual performs better when an audience is watching than when the individual performs the behavior alone. This typically occurs when people are performing a task for which they are skilled.
36.6K
Nuclear Stability03:18

Nuclear Stability

Protons and neutrons, collectively called nucleons, are packed together tightly in a nucleus. With a radius of about 10−15 meters, a nucleus is quite small compared to the radius of the entire atom, which is about 10−10 meters. Nuclei are extremely dense compared to bulk matter, averaging 1.8 × 1014 grams per cubic centimeter. If the earth’s density were equal to the average nuclear density, the earth’s radius would be only about 200 meters.
To hold positively charged protons together...
23.3K