AnalyzeDirect 
Lower back pain is a major problem throughout the world, with the highest prevalence among those aged 40–80 years. Over the coming decades, as the population ages, the global number of individuals with low back pain is likely to increase substantially. Many current treatments involve invasive surgery such as spinal disc fusion. Recent research however may provide a step towards an interesting non-surgical therapy for lower back pain.
One disease that can cause severe back pain is intervertebral disk degeneration (IVD). This disease causes the degeneration of specific cells that make up the vertebrae disc of the spine. These cells are called the nucleus pulpous (NP) cells, and they make up the majority of the disc body. It is theorized that the cause of this degeneration is chronic overloading pressure on the disc in the spine, resulting in the activation of the programmed cell death pathway called apoptosis through the caspase 3 protein. The programmed cell death pathways are a series of protein regulators that cause death of the cell from within. Currently, there is no therapy for IVD to help alleviate the pain and stop NP cell apoptotic degeneration, apart from surgeries such as spinal fusion and artificial disc replacement.
A recent study by researchers at the University of Hokkaido, published in the American Journal of Pathology, examined the caspase 3 pathway induction in two IVD models, a 3-D cell model of chronic compression and a live rabbit model of overloaded compression. This research showed that the cell death pathway is increased in both models that mimic IVD. Their results suggest that the NP cells, after compression, had an upregulated level of caspase 3 as well as other proteins that indicate the cell death pathway was turned on combined with increased NP cell death.
Decreased caspase-3 increases cell survival
The study showed that therapy designed to target and decrease the caspase 3 protein decreased NP cell degeneration and decreased other markers of apoptosis. The researchers used silencing RNA (siRNA) to decrease caspase 3 expression in IVD. siRNAs are designed to target pre-mRNA of a protein, bind to it, and lead to its degradation, thus resulting in less protein made. In the in vitro model of 3-D cell chronic compression, they compared siRNA designed to knockdown caspase 3 protein with scrambled siRNA designed to target nothing. This comparison revealed that the siRNA therapy targeting caspase 3 resulted in decreased NP cell degeneration, while the negative control with scrambled siRNA did not. This proved that the siRNA could manipulate the caspase 3 protein levels. Thus, transferring this therapy into an animal model was deemed worthwhile. In the in vivo rabbit model, one week after overloading the L4 and L5 vertebrae, they injected the anti-caspase 3 siRNA and scrambled siRNA (siRNA control rabbits). Rabbits were examined at 8 and 16 weeks post injection. To verify therapy they took MRI images of the spine. Midsagittal or midaxial MRI images of the treated discs were imaged and evaluated using the Analyze visualization and analysis software suite. This experiment showed that the rabbits with the anti-caspase 3 siRNA injected into their spine had significantly less degeneration of the NP cells than both the control rabbit groups.
This research suggests that after intervertebral disc degeneration has begun, and before invasive surgery is required, the injection of this small anti-caspase 3 siRNA could potentially reverse the damage. What is even more encouraging is that the caspase 3 siRNA did not completely knockdown the caspase 3 protein, which suggests the pathway is still functioning, just turned down near the injection site. Thus, programmed cell death is not completely turned off by this process. For people suffering from IVD, relief could be in the not too distant future and could consist of siRNA therapy injections rather than highly invasive surgery.
Tags: Intervertebral Disk Degeneration, Lower Back Pain, Programmed Cell Death