The DRG model
The dorsal root ganglion (DRG) consists of cell bodies of sensory neurons, bundles of myelinated axons, blood vessels and capsular connective tissue. In addition, each neuronal cell body is surrounded by satellite cells associated with a basal lamina. The neurons are subdivided into two types of neurons, A-cells (large light) and B-cells (small dark) neurons. The large light cell population gives rise to the fast-conducting myelinated Aα and Aβ mechanoreceptive fibres, while small dark neurons comprise mostly DRG neurons with Aδ and C fibres which convey nociceptive signals. Our work provides evidence for the importance of all three morphological constitutents, i.e., blood vessels, axons and number of neuronal cell bodies, in the phenotypic response of the ganglion to either proximal nerve root or distal spinal nerve lesion.
The morphology of lumbosacral DRGs cells remain essentially constant from 3 to 24 months of age (Mohammed and Santer, 2001). However, there are disagreements about the numbers of DRG neurons in the rat. Quantitative studies revealed different changes with age and loss of 7,000-11,500 neurons after sciatic nerve section at 4 weeks of age in the rat (Schmalbruch, 1987). Schmalbruch also pointed out that the counts of DRG cells in rat lumbar ganglia differ by as much as three-fold in different studies and that no study agrees with others. We believe that a major difficulty in this regard is that different counting methods lead to different estimates of cell numbers. It is likely that serial section reconstruction methods are more accurate for estimating the number of DRG neurons than counting profiles every third or sixth sections which can lead to biased numbers.
DRG neurons exhibit weak axonal growth after axotomy of their central processes running in nerve roots. In contrast, vigorous regeneration is observed after spinal or sciatic nerve injury (for review see Ramer et al., 2001). While peripheral rodent axons grow at a rate of 2-3 mm/day after lesion, the regeneration of nerve root axons does not exceed 1 mm/day. Interestingly, the elongation rate of dorsal root axons is doubled and some fibers may even overcome the inhibition at the dorsal root entry zone if the peripheral nerve is lesioned prior to rhizotomy (Chong et al., 1999). Damage to the peripheral sciatic nerve results in neuronal de-novo-expression of growth associated proteins (e.g., GAP-43), cytoskeletal proteins such as tubulin and actin, growth-related neuropeptides and cell adhesion molecules (Donnerer, 2003; Costigan et al., 2002). In general, these axotomy-induced changes in gene expression are significantly weaker in response to nerve root lesion when compared to peripheral nerve lesion, and some molecules, e.g., GAP-43 or certain types of sodium channels, are not regulated at all (Sleeper et al., 2000).
Seite Drucken
PDF Version
