The Effects of NPY1 Receptor Antagonism on Intervertebral Disc and Bone Changes in Ovariectomized Rats

Study Design: Basic science. Objective: To compare the effects of a neuropeptide Y1 receptor antagonist (NPY-1RA) to estrogen on maintaining vertebral bone microarchitecture and disc height in a rat model of menopause. Methods: This study was an institutional animal care approved randomized control study with 104 ovariectomized rats and 32 intact control animals. Comparison of disc height, trabecular bone, body weights, circulating levels of NPY and estrogen, and distribution of Y1 receptors in the intervertebral disc in an established rodent osteoporotic model were made at baseline and after 2, 4, and 8 weeks after receiving either an implant containing estrogen or an antagonist to the neuropeptide Y1 receptor. Data was compared statistically using One-way analysis of variance. Results: Circulating levels of estrogen increased and NPY decreased following estrogen replacement, with values comparable to ovary-intact animals. NPY-1RA-treated animals had low estrogen and high NPY circulating levels and were similar to ovariectomized control rats. Both NPY-1RA and estrogen administration were able reduce, menopause associated weight gain. NPY-1RA appeared to restore bone formation and maintain disc height, while estrogen replacement prevented further bone loss. Conclusion: NPY-1RA in osteoporotic rats activates osteoblast production of bone and decreased marrow and body fat more effectively than estrogen replacement when delivered in similar concentrations. Annulus cells had NPY receptors, which may play a role in disc nutrition, extracellular matrix production, and pain signaling cascades.

Multiphasic Finite Element Analysis of Physical Signals and Solute Transport in the Human Intervertebral Disc

A 3D finite element model for charged hydrated soft tissue containing charged/uncharged solutes was developed based on the multi-phasic mechano-electrochemical mixture theory [1–2]. This model was applied to analyze the mechanical, chemical and electrical signals within the human intervertebral disc under mechanical loading. The effects of tissue composition and material property on the physical signals and the transport of fluid, ions and nutrients were investigated. This study is important for understanding disc biomechanics, disc nutrition and disc mechanobiology.

Influence of Fixed Charge Density Magnitude and Distribution on the Intervertebral Disc: Applications of a Poroelastic and Chemical Electric (PEACE) Model

A 3-dimensional formulation for a poroelastic and chemical electric (PEACE) model is presented and applied to an intervertebral disc slice in a 1-dimensional validation problem and a 2-dimensional plane stress problem. The model was used to investigate the influence of fixed charge density magnitude and distribution on this slice of disc material. Results indicated that the mechanical, chemical, and electrical behaviors were all strongly influenced by the amount as well as the distribution of fixed charges in the matrix. Without any other changes in material properties, alterations in the fixed charge density (proteoglycan content) from a healthy to a degenerated distribution will cause an increase in solid matrix stresses and can affect whether the tissue imbibes or exudes fluid under different loading conditions. Disc tissue with a degenerated fixed charge density distribution exhibited greater solid matrix stresses and decreased streaming potential, all of which have implications for disc nutrition, disc biomechanics, and tissue remodeling. It was also seen that application of an electrical potential across the disc can induce fluid transport.

Pathophysiology of lumbar disc degeneration: a review of the literature

Lumbar disc degeneration occurs because of a variety of factors and results in a multitude of conditions. Alterations in the vertebral endplate cause loss of disc nutrition and disc degeneration. Aging, apoptosis, abnormalities in collagen, vascular ingrowth, loads placed on the disc, and abnormal proteoglycan all contribute to disc degeneration. Some forms of disc degeneration lead to loss of height of the motion segment with concomitant changes in biomechanics of the segment. Disc herniation with radiculopathy and chronic discogenic pain are the result of this degenerative process.