Potential Treatment for Back Pain with Senolytics

Senolytic therapy lowers inflammatory indicators in an intervertebral disc cell culture.

Back discomfort is a common problem.

Around 80% of people have experienced back pain at some point in their lives or will do so in the future. People spend a lot of time with a disability because of this [2].

Degeneration of the intervertebral disc frequently causes the pain. The structures in the spine known as intervertebral discs act as cushions between the vertebrae of the spinal column. Although this is a widespread issue, the cellular and molecular mechanisms underlying it are still poorly understood.

Researchers have discovered a connection between inflammation and the discomfort brought on by intervertebral disc degeneration. Senescence-associated secretory phenotype (SASP), a group of chemicals that senescent cells are known to produce in excess, is one of the causes of this inflammation and discomfort.

Some researchers are investigating whether targeting senescent cells can aid in the treatment of low back pain because prior research indicated that the buildup of senescent cells contributes to the initiation and development of intervertebral disc degeneration.

Senolytics, specifically RG-7112 and o-Vanillin, which have been previously characterized as having serotherapeutic activity in degenerated intervertebral disc cells [3, 4], were used by the researchers to target senescent cells in this study. These senolytic substances affect many cellular processes.

The premise of this study is that simultaneous targeting of many cellular pathways and processes will have a more beneficial impact on senescent, degenerative intervertebral disc cells than a single medication. This might also make it possible to provide each treatment at a lower dose, so reducing adverse effects.

The combination of RG-7112 and o-Vanillin treatment

The authors of this study attempted to mimic the natural environment of degenerative intervertebral disc cells in the human body. They obtained cells from people who experience lower back discomfort and degenerating intervertebral discs. These cells were grown in the lab using a 3D culture paradigm, and senescence was induced.

First, they proved that the expression of SASP factors and other senescence-related molecules is decreased when RG-7112 and o-Vanillin are treated independently. They then ran an experiment to see if their effects would add up. They experimented with several mixtures of various concentrations of RG-7112 and o-vanillin and discovered a concentration that performed better than each molecule alone.

Senolytic therapies decreased the amount of senescent cells, as demonstrated by their future investigations. While not hazardous to the healthy, non-senescent cells, the combined RG-7112 and o-Vanillin therapy increased the rate of programmed death of the senescent cells the most. Additionally, the SASP was decreased as a result of this combination.

The expression of the elements involved for disc innervation was another topic of study. Increased levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), markers linked to the sprouting and growth of neurites, which project from the bodies of neurons, were seen in painful, degenerating intervertebral discs. Since healthy intervertebral discs often lack nerve tissue and blood vessels, such innervation is a characteristic of painful and degenerative discs [5].

Researchers examined the effects of RG-7112 and o-Vanillin on those elements and on neurites both together and separately. They discovered that the mixture reduced neurite development, BDNF, and NGF.

Accordingly, the authors propose that the removal of senescent cells by senolytics causes a decrease in NGF and BDNF, which in turn causes a decrease in neurite sprouting and, ultimately, a decrease in back pain.

Senolytic treatments for degenerative disc disease

Overall, when compared to a single therapy, the combination of RG-7112 and o-Vanillin was more effective at reducing senescence and SASP. As a result, there were more senescent cells that experienced programmed cell death as well as more growing non-senescent cells.

But since this study uses lab-grown cells, it is crucial to do more studies using vertebrate animals that are alive and have accessible discs.

There are more senolytics being studied for intervertebral disc degeneration besides RG-7112 and o-Vanillin. Mice have been used to test a dasatinib and quercetin combo. Multiple injections of this mixture into elderly animals revealed decreased SASP in the intervertebral discs [6].

A human clinical trial that targets senescent cells with the goal of enhancing older persons' bone health is currently testing dasatinib, quercetin, and fisetin together. These treatments could possibly aid millions of people with back pain if they are found to be effective.