The structure in the back that seems mainly responsible for low back pain production is the intervertebral disc. An intervertebral disc is arranged between two adjacent vertebrae. The intervertebral disc is typically flexible and allows for motion between the adjacent vertebrae. It is formed by a ring of connective tissue that mainly comprises collagen, and a semi-liquid center comprising e.g. collagen and proteoglycans. The ring is called annulus fibrosus and the center is called nucleus pulposus.
Already at the age of 20-30 years, the intervertebral disc of a human starts to undergo ageing, a process often called disc degeneration. During the ageing process the intervertebral disc may leak or herniate and produce symptoms like low back pain and sciatica. The ageing of the intervertebral disc usually ends at the age of 60-80 years. At this stage, the intervertebral disc has been transformed to solid and dense connective tissue. When this occurs, the intervertebral disc will typically not produce symptoms anymore since it is less likely to leak or herniate. The ageing of the intervertebral disc further implies a reduction in disc height and a reduction of mobility of the spine.
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The composition for use in the treatment of intervertebral disc-related pain may be formulated such that it may be administered in a therapeutically effective amount by a local injection to an intervertebral disc.
The concept of the present invention is to reduce the intervertebral disc-related pain by accelerating the ageing of an intervertebral disc thereby rendering the intervertebral disc stiffer, e.g. by transformation of the intervertebral disc into solid and dense connective tissue. The transformation of an intervertebral disc into solid and dense connective tissue makes it more stable, and consequently, the intervertebral disc obtains a reduced range of motion. An intervertebral disc transformed into solid and dense connective tissue will neither allow any fluid component to leak out from the disc space, e.g. onto the outer surface of the annulus fibrosus, nor allow nerves to grow into the intervertebral disc.
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The lactic acid may interfere negatively with the function of the cells of the intervertebral disc, in particular the cells that produce the proteoglycans necessary for preventing the disc from ageing.
Ageing of an intervertebral disc is initiated by a reduced supply of nutrients and oxygen via diffusion from the blood vessels in the adjacent vertebrae and from surrounding structures. This will gradually induce an accumulation of metabolic waste products in the intervertebral disc, such as in the nucleus pulposus. One kind of metabolic waste product that may be present is lactic acid.
Lactic acid may contribute to several mechanisms that will render cellular death in the intervertebral discs, such as intracellular fat accumulation, mitochondrial swelling, chromatin clumping, and liberation of excitotoxic glutamate.
Lactic acid may liberate PGE2 causing inflammation and production of connective tissue. Further, lactic acid may stimulate liberation of TGF-beta, which in turn stimulates fibroblasts to produce collagen.
Lactic acid may also contribute to disseminated intravascular coagulation and consumption coagulopathy, which increases the tendency of red blood cells to aggregate, forming “blood sludge” and makes red blood cells more rigid, in turn, increasing the viscosity of the blood and impairing circulation in the small vessels.
Thus, an increase in the concentration of lactic acid in an intervertebral disc by administration of a composition comprising lactic acid into the disc space of the intervertebral disc would therefore accelerate the ageing of the disc and induce transformation of the nucleus pulposus into connective tissue.
Ageing of the intervertebral disc, including transformation of the nucleus pulposus into connective tissue, renders the intervertebral disc stiffer, and by administering a composition comprising lactic acid the ageing may be accelerated in a controllable way. Typically, the concentration of lactic acid may be increased in an intervertebral disc, more specifically in the disc space, in order to accelerate the ageing.
The inventor has found that a composition comprising lactic acid and having a pH below 4 induces a marked transformation of the intervertebral disc, thus making it stiffer. The marked transformation has been interpreted as an accelerated ageing of the intervertebral disc by transformation of the nucleus pulposus to connective tissue. Consequently, the inventor expects improvements for a patient with regard to intervertebral disc-related pain if a composition comprising lactic acid and having a pH below 4, is administered into the nucleus pulposus of the intervertebral disc resulting in an increased concentration of lactic acid inside the disc space.