Causes and consequences of sympathetic basket formation in dorsal root ganglia

Injury to peripheral nerves can result in severe and intractable neuropathic pain, and in some cases the symptoms are sympathetically maintained. In recent years much effort has been put into elucidating the anatomical nature of nerve injury-induced sympathetic-sensory coupling. The demonstration of sympathetic sprouting into dorsal root ganglia (DRG) of nerve-injured rats has led to the suggestion that this phenomenon might underlie sympathetically-maintained pain. As a result, several studies have been undertaken to determine what factor or factors are responsible for the sprouting, and for the formation of abnormal sympathetic terminal arborizations or 'baskets' around some DRG neurons. In this review we examine in particular the roles of nerve growth factor (NGF) and the cytokines leukemia inhibitory factor (LIF) and interleukin-6 (IL-6), as these have all been shown to contribute to sympathetic sprouting. We also stress the role of satellite cells within axotomized DRG, as these have been shown to express not only neurotrophin mRNA, but also the low-affinity neurotrophin receptor p75. We propose a mechanism for sympathetic sprouting in the DRG involving; (i) the activation of satellite cells on the DRG by a factor such as LIF or IL-6, and (ii) the generation of a sympathetic axon-guiding gradient by p75-bound neurotrophins on the activated satellite cells. We also highlight the possibility that a sympathetic sprouting signal may be derived from the periphery, as NGF, LIF and IL-6 are all produced as a result of Wallerian degeneration, and can be retrograde transported to the DRG. The possible relevance of sympathetic sprouting in the DRG to neuropathic pain is also discussed.