Stimulation Of Lumbar Sympathetic Trunk Research Articles

Sympathetic modulation of hindlimb muscle contractility is altered in aged rats

It has recently been demonstrated that reflex excitation of muscle sympathetic nerves triggered by muscle contraction contributes to the maintenance of tetanic force (TF) in rat hindlimb muscles. We hypothesized that this feedback mechanism between the contraction of hindlimb muscles and the lumbar sympathetic nerves declines during aging. In this study, we examined the contribution of sympathetic nerves on skeletal muscle contractility in young adult (4–9 months old, n = 11) and aged (32–36 months old, n = 11) male and female rats. The tibial nerve was electrically stimulated to measure the TF of the triceps surae muscles resulting from motor nerve activation before and after cutting or stimulating (at 5–20 Hz) the lumbar sympathetic trunk (LST). The TF amplitude decreased by cutting the LST in the young and aged groups; however, the magnitude of the decrease in TF following transection of the LST in the aged rats (6.2%) was significantly (P = 0.02) smaller compared with that in the young rats (12.9%). The TF amplitude was increased by LST stimulation at ≥ 5 Hz in the young and ≥ 10 Hz in the aged groups. The overall TF response to LST stimulation was not significantly different between the two groups; however, an increase in muscle tonus resulting from LST stimulation, independent of motor nerve stimulation, was significantly (P = 0.03) greater in aged compared with young rats. The sympathetic contribution to support motor nerve-induced muscle contraction declined, whereas sympathetic-mediated muscle tonus, independent of motor nerve activity, was augmented in aged rats. These changes in sympathetic modulation of hindlimb muscle contractility may underlie the reduction of skeletal muscle strength during voluntary contraction and rigidity of motion during senescence.

Basic Science (30)

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.

Sympathetic-sensory coupling after L5 spinal nerve lesion in the rat and its relation to changes in dorsal root ganglion blood flow

Transection of the L5 spinal nerve in rats results in allodynia- and hyperalgesia-like behavior to mechanical stimulation which are thought to be mediated by ectopic activity arising in lesioned afferent neurons mainly in the dorsal root ganglion (DRG). It has been suggested that the neuropathic pain behavior is dependent on the sympathetic nervous system. In rats 3–56 days after L5 spinal nerve lesion, we tested 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 we measured blood flow in the 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 which did react to LST stimulation, responses occurred only at high stimulation frequencies (likely to be above the physiological range), and they could be mimicked by non-adrenergic vasoconstrictor drugs (angiotensin II, vasopressin). Excitatory responses to LST stimulation were closely correlated with the stimulation-induced phasic vasoconstrictions in the DRG. We therefore hypothesized that the activation of lesioned afferents might be brought about indirectly by an impaired blood supply to the DRG. To test this hypothesis we induced a strong and sustained baseline vasoconstriction in the DRG by blocking endothelial nitric oxide synthesis with N G-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. In the present study, 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 the 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.

Interaction of sympathetic vasoconstriction and antidromic vasodilatation in the control of skin blood flow.

We studied the interaction between the vasoconstriction evoked by postganglionic sympathetic neurones (sympathetic vasoconstriction) and the vasodilatation mediated by small-diameter afferent neurones (antidromic vasodilatation) in hairless skin of anaesthetized rats kept under controlled conditions. In all animals both the lumbar sympathetic trunk (LST) and the ipsilateral dorsal root (DR) L5 were surgically exposed, sectioned and electrically stimulated using different protocols. This experimental approach results in the exclusive and selective activation of sympathetic efferents and primary afferents respectively. Blood flow responses were measured using laser Doppler flowmetry. Sectioning the LST resulted in a pronounced increase in cutaneous blood flow by 112+/-15% (mean+/-SEM, n=25) indicating that ongoing sympathetic vasoconstrictor activity had been abolished. When a brief antidromic vasodilatation was produced by DR stimulation with 10-15 pulses at 1 Hz with C-fibre intensity during a sustained sympathetic vasoconstriction, peak blood flow reached preconstriction levels at LST stimulation frequencies of < or = 3 Hz. By contrast, antidromic vasodilatation was reduced at sympathetic stimulation frequencies of > or = 5 Hz and absent when stimulating the LST with 20 Hz. A similar response characteristic was obtained when LST and DR stimulation were started simultaneously. Continuous DR stimulation with 0.1 Hz evoked a substantial increase in cutaneous blood flow by 38+/-10% (mean+/-SEM, n=8) to a new baseline level. When sympathetic vasoconstriction was elicited on this background DR stimulation, the responses were smaller at all sympathetic frequencies. However, the maximum decrease in blood flow was significantly smaller than the controls at LST stimulation with < or = 3 Hz but not at higher frequencies. We conclude that sympathetic vasoconstriction and antidromic vasodilatation are competitive influences in the control of cutaneous blood flow. At low levels of cutaneous sympathetic vasoconstrictor activity, which probably prevail under resting conditions in the absence of cold stress, antidromic vasodilatation overrides sympathetic vasoconstriction. At high levels of cutaneous sympathetic activity, which may be reached in normal life under the conditions of severe cold, sympathetic vasoconstriction can suppress antidromic vasodilatation almost totally.

Sympathetically induced paradoxical increases of the cutaneous blood flow in chronically inflamed rats

In adjuvant arthritic (AA) rats, an abnormal responsiveness of nociceptors (C-fibre polymodal receptors) to sympathetic activities, i.e., α 2-adrenoceptor mediated activation of C-fibre polymodal receptors (CPRs), has been observed. The present investigations were undertaken to determine if a similar plastic change would occur in the cutaneous vascular system in the rat chronic inflammation model. The vascular responses were measured by a laser-Doppler flowmeter in the hindpaw skin of the AA rats after electrical stimulation of lumbar sympathetic trunk (sympathetic stimulation). In control non-arthritic rats, the sympathetic stimulation caused decrease in blood flow of the skin (SkBF) in all animals tested ( n = 7). On the other hand, the sympathetic stimulation in the AA rats caused both increase ( n = 15) as well as decrease ( n = 11) in SkBF. In contrast to the abnormal responsiveness of CPRs, the intra-arterial injection of noradrenaline caused the expected decrease in SkBF in all animals tested, and in no instances increases in SkBF were observed. To determine whether activation of nitric oxide (NO), which is known to be a potent endogenous vasodilatation substance, was involved in the vasodilating effect to sympathetic stimulation, an inhibitor of NO synthase, N G-monomethyl-L-arginine (L-NMMA), was applied systemically. L-NMMA significantly increased baseline blood pressure in the control and the AA rats, but it did not significantly alter the SkBF in the control or the AA rats after the sympathetic stimulation, suggesting the NO is not a mediator in the vasoactive responses. The results of the current studies showed for the first time that electrical stimulation of the lumbar sympathetic trunk causes vasodilatation in the skin of the AA rats. This abnormal responsiveness of regional SkBF after sympathetic stimulation was not mediated by adrenergic or NO system.

Stimulation of lumbar sympathetic trunk produces vasoconstriction of the vasa nervorum in the sciatic nerve via α-adrenergic receptors in rats

The effects of repetitive electrical stimulation of a lumbar sympathetic trunk (LST) for 30 s at various frequencies and supramaximum intensity on the nerve blood flow in a sciatic nerve were studied by laser Doppler flowmetry in anesthetized Fischer-344 male rats. The response was biphasic; i.e. an initial increase and then a decrease. The maximum mean increase after 2 Hz stimulation was 22 ± 8%, while the maximum mean decrease after 20–50 Hz stimulation was 79 ± 3%, of the prestimulus control level. The initial increase, which was greater at lower frequencies and existed even after loca sympathetic denervation, was passive, and was caused by the systemic pressor response to LST stimulation. The decrease, which was nearly abolished by an i.v. α-adrenergic blocker, phentolamine (10 mg/kg), resulted from vasoconstriction in the vasa nervorum, mainly via activation of α-adrenergic receptors.

Electrical stimulation of lumbar sympathetic trunk decreases blood flow in a sciatic nerve via α-adrenergic receptors in rats

Electrical stimulation of lumbar sympathetic trunk decreases blood flow in a sciatic nerve via α-adrenergic receptors in rats

Activation of unmyelinated afferents in chronically lesioned nerves by adrenaline and excitation of sympathetic efferents in the cat.

Neuroma-in-continuity was experimentally produced in cats by suturing the proximal stump of a transected hindlimb cutaneous nerve to the distal stump of the transected tibial nerve. Eleven to 20 months afterwards single non-myelinated fibres were identified by electrical recording from filaments of the nerves proximally from the neuroma. When tested with repetitive electrical stimulation of the lumbar sympathetic trunk (LST) or i.v. injections of adrenaline, C-fibres in 14 out of 30 filaments were excited by at least one of these stimuli (12 by adrenaline, 7 by stimulation of LST). The fibres responding to LST stimulation were already substantially excited by low frequency stimulation (1-2 Hz). During systemic hypoxia known to result in reflex increases of efferent sympathetic activity responses were elicited in 4 out of 6 C-fibres. Thus, stimuli simulating physiological conditions of sympathetic activity can excite afferent C-fibres in a chronically lesioned nerve.

Activation of myelinated afferents ending in a neuroma by stimulation of the sympathetic supply in the rat

The sciatic nerve in rats was cut and ligated, and 5–18 days later pathophysiological properties of the resulting neuroma were studied. We found that afferent fibers ending in the neuroma produced prolonged discharges following repetitive stimulation of the lumbar sympathetic trunk (LST) or i.v. adrenaline. Mean latencies of activation of afferent fibers were 10 ± 2.1 sec and 12 ± 3.4 sec (mean ± S.D.) to LST stimulation and to adrenaline injection, respectively. The α-adrenergic antagonist phentolamine blocked responses to LST stimulation and adrenaline. The β-adrenergic antagonist propranolol had no effect.

Hyperpolarization of trigeminal primary afferents evoked by stimulation of lumbar sympathetic trunk and peripheral nerves

The gate control theory has emphasized primary afferent hyperpolarization (PAH) as a specific determinant in the perception of a stimulus as painful. Previous studies which indicated that primary afferent depolarization (PAD) could be elicited in the trigeminal system by nonsegmental inputs suggested that this might also be the case for primary afferent hyperpolarization. Decreased excitability of trigeminal primary afferent fibers, an indirect reflection of PAH, was elicited by stimulation of the lumbar sympathetic trunk, sural, and sciatic nerves in cats. This PAH has a magnitude and time course similar to that previously demonstrated in the trigeminal system by segmental noxious inputs. We postulate that PAH is a general phenomenon related to the control of information transmission across afferent synapses rather than a phenomenon specifically related to the perception of various stimuli as painful.

Cross circulation at the small blood vessel level in the dog paw.

Small vessel responses to maximal sympathetic stimulation have been studied by establishing a cross circulation, at the small blood vessel level, between the two hind legs of the dog. This technique permitted the differentiation between vascular responses occurring upstream and downstream from the level of the cross circulation. Sciatic nerve stimulation stopped flow in both upstream and downstream arterial segments. Lumbar sympathetic trunk stimulation (which did not include all nerves supplying the digital vasculature) stopped flow in the upstream arteries, but allowed a restricted flow to continue in the downstream segments. Both lumber and sciatic nerve stimulation produced intense constriction of dorsal metatarsal and digital veins. Establishment of a cross circulation at either the dorsal metatarsal or dorsal digital vein level proved that in unstimulated vessels a retrograde flow from small vein to small artery was possible. During maximal sympathetic stimulation, constrictive closure of small veins prevented flow from occurring either upstream or downstream in metatarsal and digital veins until perfusion pressures were increased to approximately 100 mm Hg. Thus, constrictive closure of the venules protected the capillaries from the high small vein pressures developed during maximal sympathetic stimulation.

Cutaneous and muscle vascular responses to electrical stimulation of lumbar sympathetic trunk in the dog.

Simultaneous vascular responses in three cutaneous (thigh, calf, footpad) and one muscle (gastrocnemius) bed of the dog's hind leg were recorded during stimulation of the ipsilateral lumbar sympathetic trunk, and correlated with the vertebral level of stimulation. Changing patterns of vascular response with successively lower stimulations was interpreted to indicate the levels of preganglionic entry of vasomotor fibers into the sympathetic trunk. Significant variations in the anatomic patterns of vasomotor pathways were found. In a few animals vasoconstrictor fibers innervating only the proximal portions of the extremity were found in the more rostral portions (L2-L3) of the trunk. In others, however, these same segments of the trunk carried rich innervation to the most distal regions of the extremity. In a majority of animals, the most effective cutaneous vasomotor innervation entered the trunk between L3 and L5. There were notable instances of entry as low as the L6–L7 interganglionic segment. Both vasoconstrictor and vasodilator responses were elicited in the gastrocnemius muscle, frequently by stimulation at different levels of the trunk in a given animal. The dilator responses were readily abolished by intravenous administration of atropine, leaving constrictor reactions relatively unaffected.