Basic Science (30)
Authors: Häbler H.‐J. , Eschenfelder S. , Liu X.‐G. , Jänig W. 
Published: September 2010

Sympathetic‐sensory coupling after L5 spinal nerve lesion in the rat and its relation to changes in dorsal root ganglion blood flow. (Christian‐Albrechts‐Universität, Kiel, Germany) Pain 2000;87:335–345.In rats 3‐56 days after L5 spinal nerve lesion, the authors of this study tested the responses of axotomized afferent fibers recorded in the dorsal root of the lesioned segment to norepinephrine (NE, 0.5 μg/kg) injected intravenously and to selective electrical stimulation of the lumbar sympathetic trunk (LST). In some experiments, blood flow was measured in the dorsal root ganglion (DRG) by laser Doppler flowmetry. The majority of lesioned afferent fibers with spontaneous activity responded to neither LST stimulation (82.4%) nor NE (71.4%). In those that did react to LST stimulation, responses occurred only at high stimulation frequencies and they could be mimicked by nonadrenergic vasoconstrictor drugs (angiotensin II, vasopressin). Excitatory responses to LST stimulation were closely correlated with the stimulation‐induced phasic vasoconstrictions in the DRG. Therefore, the activation of lesioned afferents might be brought about indirectly by an impaired blood supply to the DRG. To test this hypothesis, a strong and sustained baseline vasoconstriction in the DRG was induced by blocking endothelial nitric oxide synthesis with NG‐nitro‐L‐arginine methyl ester (L‐NAME) applied systemically. L‐NAME enhanced baseline vascular resistance in the DRG about threefold and also increased stimulation‐induced vasoconstrictions. After L‐NAME, the majority of axotomized neurons with spontaneous activity were activated by LST stimulation (76%) or NE (75%). Again, activations closely followed stimulation‐induced phasic vasoconstrictions in the DRG provided that a critical level of vasoconstriction was exceeded. Inhibitory responses to LST stimulation were generally rare and could be reversed to activation by prolonged stimulation or after L‐NAME. These results show that sympathetic‐sensory coupling occurs only in a minority of axotomized afferents after L5 spinal nerve injury. Like previous studies, they cast doubt on the notion that L5 spinal nerve lesion is a good model for sympathetically maintained pain. Since responses of lesioned afferent neurons to LST stimulation and NE could be provoked with high reliability after inducing vasoconstriction in the DRG, and since they mirrored stimulation‐induced vasoconstrictions in the DRG, it appears that in this model the association of sympathetic activity with afferent discharge occurs mainly when perfusion of the DRG is impaired. Comments by Marshall Devor, PhD.Animal research has revealed that massive ectopic afferent discharge is generated in the dorsal root ganglion (DRG) following nerve injury. This source of ectopic firing is in addition to activity that may be generated at the nerve injury site (Tinel sign). The combined impulse barrage is almost certainly an important cause of neuropathic pain. It has been discovered recently that the intensity of the ectopic DRG barrage is modulated by sympathetic efferent activity. This is a potential link between sympathetic activity and symptomatology in sympathetic related pain conditions such as complex regional pain syndrome/reflex sympathetic dystrophy. But what is the mechanism of the sympathetic‐sensory coupling? Considerable evidence indicates that axotomized DRG neurons become abnormally adrenosensitivity. Habler et al now point out an additional, indirect, coupling mechanism … modulation of intrinsic DRG blood flow. That is, sympathetic activity may reduce DRG blood flow inducing partial ischemia, with the ischemia causing neural excitation. This finding may also have broader implications as spinal pathology can also compromise DRG blood flow. Might low back pain and sciatica, for example, derive from this same process? It is surprising that ectopic firing in the DRG has played so little part in clinical thinking and practice in patients with neuropathic pain. So far.