Adrenergic innervation of rat sensory ganglia following proximal or distalpainful sciatic neuropathy: distinct mechanisms revealed by anti-NGF treatment

Sympathetic axons invade dorsal root ganglia (DRG) following nerve injury, and activity in the resulting pericellular axonal 'baskets' may underlie pa inful sympathetic-sensory coupling. Sympathetic sprouting into the DRG may be stimulated by nerve growth factor (NGF). To test this hypothesis, we inv estigated the effect of daily anti-NGF administration an pain and on sprout ing in the DRG induced by chronic sciatic constriction injury (CCI) or L5 s pinal nerve ligation (SNL). These models have been shown to differ subtly i n the onset of pain behaviours and adrenergic sprouting, and we now demonst rate a fundamental difference in the way sympathetic axons invade the DRG: after CCI, perivascular noradrenergic collaterals sprouted into the DRG in a manner dependent upon peripherally derived NGF. In contrast, after SNL, r egenerating sympathetic axons were diverted towards the DRG from the spinal nerve by the obstructing ligature, and this effect was only moderately imp eded by anti-NGF. The differential dependence on anti-NGF suggests that adr energic innervation of the DRG after SNL and CCI may reflect regenerative a nd collateral sprouting, respectively. Pain behaviour was similarly affecte d: anti-NGF completely prevented CCI-induced thermal hyperalgesia and mecha noallodynia, but the same treatment only partly relieved these symptoms fol lowing SNL. These differences emphasize that although CCI and SNL may resul t in similar behavioural abnormalities, the underlying mechanisms may be go verned by distinct processes, differentially dependent on peripheral NGF. T hese mechanistic differences will have to be considered in the development of appropriate treatment strategies for neuropathic pain produced by differ ent types of pathology.