Throughout this text, a distinction has been made between intervertebral disc disease (IVDD) and intervertebral disc herniation (IVDH). The main reason for this distinction is to differentiate clinical signs (pain and paresis) resulting from compressive lesions affecting the spinal cord and/or nerve roots (or well-innervated paradiscal structures such as the dorsal longitudinal ligament [1]), which are due to actual displacement of the disc, from clinical signs attributable to degenerative change in an intact, nonbulging intervertebral disc (IVD), leading to internal pain generation within this structure. A fair question to ask is whether patients can suffer symptoms of pain merely as a consequence of the degenerative processes that might be occurring in one or more IVDs [2].

A further complication that should be taken into account with regard to the generation of pain of discal origin is that, with the onset of age, the normal sequence of events in the IVD is for the disc cells to synthesize an altered form of aggrecan with smaller chondroitin sulfate (CS) side chains. Aggrecan is the major space-filling disc proteoglycan which conveys important weight-bearing properties to the nucleus pulposus (NP) [3]. Since there are no known mammalian chondroitinases (enzymes which degrade the CS side chains of aggrecan), this selective depolymerization process is the consequence of a change in how the aggrecan is biosynthesized by the disc cells and not due to a degradative event and is interpreted as an aging phenomenon. However, it still diminishes the biomechanical competence of the IVD as a weight-bearing structure. The consequence of this reduction in the hydrodynamic size and number of the CS chains attached to the aggrecan core protein is that the degree of hydration, which aggrecan can entrap in the NP, is reduced, leading to dehydration of this tissue with aging and a reduction in disc height. There may also be a compensatory increase in the synthesis of collagen which may lead to a further reduction in vertebral column flexibility. Axial loading to the vertebral column in these instances can lead to bulging of the annulus fibrosus (AF) since it is now required to take up a greater proportion of the compressive axial load. If annular nerve endings are indeed nociceptive, then this altered annular loading potentially can provide a mechanism for annular pain generation in an otherwise intact but aged IVD. With aging, aggrecan can also undergo proteolytic degradation of its core protein through the action of matrix metalloproteinases, leading to fragmented forms of aggrecan devoid of their G1 N-terminal domains which formerly would have facilitated the interaction of aggrecan with hyaluronan to form massive macromolecular ternary complexes greater than 20 megadaltons in size [3]. In the healthy disc, these arrays are entrapped within the type II collagen network within the NP, and collectively, these provide hydrodynamic and viscoelastic weight-bearing properties to the NP of the composite disc structure. This fragmentation process constitutes part of the degradative events that occur in disc degeneration with normal aging. Traumatic overload of the biomechanically incompetent disc under such circumstances can lead to pathological failure of annular lamellae and extrusion of NP material into the vertebral canal. Such pathological change is therefore superimposed on normal age-related changes in disc composition and functional properties. A further consequence of the diminution of discal aggrecan with aging is that a significant fall in the intradiscal hydrostatic properties occurs, and this can promote ingrowth of nerves from the outer AF into the degenerate IVD. It remains controversial, however, as to whether these are nociceptive and contribute to discal pain generation. Age-related changes in disc composition are well documented in the chondrodystrophic canine breeds. Traumatic failure of discal components in the biomechanically compromised aged canine IVD may lead to extrusion of annular and nuclear material into the vertebral canal.