1, degenerative changes of the lumbar disc Degenerative changes of the lumbar disc are an important cause of lumbar disc herniation. Degenerative changes of the spine in the population are extremely uneven, and part of the lumbar disc degeneration starts in youth, and the incidence of lumbar disc herniation is high in this part of the population. It is generally accepted that lumbar disc degeneration is caused by dynamic loading of the lumbar discs. Adams et al. performed kinematic loading tests on the cadaveric spine, simulating slow walking and found a 13–36% reduction in hydrostatic pressure in the nucleus pulposus. The ability of the disc to act as a hydrostatic “cushion” depends on the water content in the nucleus pulposus. The nucleus pulposus is like a sealed hydrodynamic system, where the fluid pressure increases when the volume increases and decreases when the volume pressure decreases. A pressure equal to body weight can drain 10 – 15% of the water from a cadaveric disc in 4h. MRI shows a 20% decrease in lumbar disc volume (water content) in humans after a day of activity. The loss of water from the nucleus pulposus reduces the pressure, and the pressure on the disc is transferred to the annulus fibrosus. The highly concentrated pressure can cause structural disruption of the annulus fibrosus leading to fissure formation. Other biological studies have shown that the distribution of disc elasticity coefficients is uniformly symmetrical in normal subjects, whereas the degenerated disc annulus fibrosus has the lowest elasticity coefficient in the posterior part, where lumbar disc herniation often occurs in clinical practice, which may be related to the pathogenesis of lumbar disc herniation. The internal mechanics of the disc depend on the loading history and the applied load, which influences the degenerative disc degeneration. The exact mechanism by which normal or degenerated discs produce their effects. Such studies may use certain drugs to treat and prevent degeneration of lumbar discs. 2. Lumbar disc herniation causes non-bacterial inflammation and immune response. Lumbar disc herniation is often secondary to a nonbacterial inflammatory response. Mccarron’s injection of homogeneous nucleus pulposus samples into the canine epidural cavity with saline as a control revealed a severe inflammatory response under the microscope. considerable phospholipase A2 activity was found in lumbar disc extracts. This enzyme is the rate-limiting enzyme for prostaglandins and interleukins produced by cells at the site of inflammation. It can be hypothesized that once this enzyme is released from the confines of the disc they can contact the nerve roots and cause inflammation secondary to inflammatory mediators via action on phospholipids in the nerve cell membrane producing nerves or via enzyme production, acting on injurious receptors within the annulus fibrosus or epidural space to produce clinical symptoms. Further studies found that free herniated lumbar discs had higher prostaglandin levels than herniated lumbar discs, with the lowest prostaglandin levels in bulging herniated lumbar discs. Prostaglandin levels were higher in positive straight leg raise tests than in negative herniated lumbar discs. Prostaglandins are one of the most potent naturally occurring inflammatory mediators, and they are critical in the regulation of cellular function factors. Prostaglandins modulate the inflammatory effects produced by herniated lumbar discs, especially in the discharge symptoms produced by straight leg raising. Moreover, an intact fibrous annulus provides isolation and protection against inflammatory irritation produced by herniated lumbar discs. Evidence of vascular endogenesis, granulation and fibrous tissue proliferation in surgically removed lumbar discs has been established, and there is data that the nucleus pulposus protrudes into the spinal canal through a normal inflammatory response to a repair process. If the contents of the nucleus pulposus are considered “foreign”, this can cause a chronic inflammatory response. Inflammation and neovascularization of the herniated material can cause phagocytosis and resorption processes. Doita’s ex vivo cell culture and biological examination of surgically removed herniated discs revealed endogenous granulation tissue with angiogenesis at the edges of fibrocartilage fragments. Anti-interleukin–I, intracellular adhesion molecule–I, lymphocyte-associated functional antigen, and basal fibroblast growth factor were expressed on monocytes infiltrating into the herniated disc, causing neointima formation and inflammation. The lumbar intervertebral disc is the largest avascular unit in adults. The presence of neovascularization and inflammatory cells in herniated lumbar discs suggests that mechanization is not a major process in the development of herniated lumbar discs, producing mainly resorptive processes during the healing phase. This may be one explanation affecting the finding of spontaneous disappearance or reduction of herniated lumbar discs in the spinal canal and the reduction of symptoms without surgical treatment. Studies have shown that both humoral and cellular immune status are abnormal in patients with lumbar disc herniation. Zhang Qiang et al. measured cerebrospinal fluid and serum immunoglobulins in patients with lumbar disc herniation and normal controls by radioimmunoassay. The results showed that the cerebrospinal fluid and serum immunoglobulins increased gradually as the pathological changes of lumbar disc herniation increased. The bulging type only caused an increase in cerebrospinal fluid immunoglobulins, while the ruptured and free types caused significant increases in both cerebrospinal fluid and serum. The mechanical compression of the nerve roots by the protruding disc and the autoimmune inflammatory changes can lead to the destruction of the blood-brain barrier and the increase of capillary permeability in the nerve roots, and the infiltration of plasma proteins into the cerebrospinal fluid; collagen type I and II and glycoprotein in the disc tissue are potential autoantigens, which can stimulate the body to produce late hypersensitivity T lymphocyte and cytotoxic T cell-mediated cellular immune reaction, leading to early degeneration of the intervertebral disc, which in turn generates an immune response under the continuous action of T and B lymphocytes and disc antigens, manifested by elevated blood cell immunoglobulins; demyelinating degenerative material caused by nerve root damage and disc antigenic material entering the cerebrospinal fluid can stimulate the production of immunoglobulins by immunoreactive cells of the central nervous system. Therefore, it is believed that immune inflammatory changes of nerve roots are an important cause of sciatica, and surgical treatment of lumbar disc herniation can not only release mechanical compression of nerve roots, but also interrupt the immune response caused by intervertebral disc tissue. 3, mechanical compression formed by lumbar disc herniation In 1934, Mixter and Barr pointed out that lumbar disc tissue herniated into the spinal canal to compress and stimulate the nerve roots causing sciatica. This concept has been widely accepted over the decades and has formed the neuroanatomical basis of lumbar disc herniation. When a posterior lateral disc herniation can invade the posterior root ganglion. smith found that the spinal nerve roots could move 2–5 mm within the intervertebral foramen during straight leg raising. this normal movement may be limited if there is restriction or entrapment of the nerve. Irritation and inflammation of the nerve root will occur as the nerve attempts to elongate and stretch away from its course of motion. With slow compression of the nerve comes venous injury first, then capillary and finally arterial injury. Mechanical compression of the spinal nerve causes sensitive changes in somatic evoked potentials, and the duration of compression is significantly correlated with decreased amplitude and increased latency. An anatomical study of the human cauda equina by Cohen et al. found, and confirmed by MRI, that within the cauda equina the nerve roots are arranged in a very ordered, symmetrical laminar pattern. The most posterior nerve component within the cauda equina dural sac at the level of L5S1 is the S5 nerve root, and further forward are S4, S3, S2, and S1. After these components are pushed further at L4–5, the L5 nerve root enters anterolaterally. In any case the motor fiber component is in the anterior middle and the larger fuller sensory component is in the posterior lateral side. The two are always positioned adjacent to each other and form a small angle. This position occurs strictly in the posterior root ganglion. For one nerve root or cauda equina it does not occur uniformly in the posterior root ganglion. Uneven compression of one nerve root or cauda equina may cause asymmetric compression of the sensory or motor component of one or more adjacent nerve root components. This adds to the complexity of clinical symptoms and may lead to differences in clinical presentation between affected patients, as well as changes in clinical symptoms in the same patient at different times. In conclusion, current studies suggest that mechanical compression of the herniated lumbar disc and chemical irritation from the herniated lumbar disc material are the causes of sciatica.