Production of Hyperalgesic Prostaglandins by Sympathetic Postganglionic Neurons

Prostaglandin E2 and prostacyclin (prostaglandin I2) produce hyperalgesia in animals and humans. Because there is evidence that prostaglandins contribute to pain maintained by sympathetic nervous system activity, we evaluated whether sympathetic postganglionic neurons synthesize these hyperalgesic prostaglandins, and whether production of prostaglandins by these neurons can contribute to sensitization of primary afferent nociceptors. Intradermal injection of arachidonic acid but not linoleic acid, in the rat hindpaw, produces a decrease in mechanical nociceptive threshold. This hyperalgesic effect is prevented by indomethacin, an inhibitor of prostaglandin synthesis or by prior surgical removal of the lumbar sympathetic chain. To test the hypothesis that sympathetic postganglionic neurons are the source of prostaglandins, we measured production of prostaglandin E2 and 6-keto-prostaglandin F1 alpha (the stable metabolite of prostacyclin) by homogenates of adult rat sympathetic postganglionic neurons from superior cervical ganglia. These homogenates produced significant amounts of prostaglandin E2 and 6-keto-prostaglandin F1 alpha, and most of this production is eliminated by neonatal administration of 6-hydroxydopamine which selectively destroys sympathetic postganglionic neurons. These results demonstrate that sympathetic postganglionic neurons produce prostaglandins, and supports further the hypothesis that the release of prostaglandins from sympathetic postganglionic neurons contributes to the hyperalgesia associated with sympathetically maintained pain.     

可视化引导下腰2交感神经节阻滞治疗下肢Buerger＇s病顽固性疼痛

目的：观察C型臂下腰2交感神经节阻滞治疗下肢血栓闭塞性脉管炎（下肢Buerger＇s病）神经病理性疼痛的疗效。方法：50例Buerger＇s病患者随机分为治疗组及对照组,在C型臂机X线引导下行患侧腰2交感神经节阻滞。结果：治疗组与对照组相比,疼痛明显缓解,视觉模拟评分（VAS）显著下降,皮肤温度明显升高,且无其他并发症发生。结论：腰2交感神经节阻滞对下肢血栓闭塞性脉管炎（下肢Buerger＇s病）神经病理性疼痛有较好的治疗效果。     

Causalgia pathogenesis and treatment

Gross and microscopic anatomical evidence indicates that pain fibers involved in causalgia are those distributed to blood vessels-possibly to the arterioles-and that, for the greater part, these fibers constitute part of the general visceral afferent system. Several investigators have reported evidence that injury to a peripheral nerve of such a type as to cause damage to the vasomotor control of any area produces the initial pain in an extremity, and it is predicated that the arteriolar constriction causing the pain is then prolonged by the sensitization of arteriolar smooth muscle to the amount of epinephrine normally in the blood. If the condition is not treated, tissue anoxia occurs to such an extent that irreversible changes take place in the affected area.Treatment of causalgia in the lower extremities is directed toward interruption of either the vasomotor or afferent supply of blood vessels by blocking or excision of the second to fourth lumbar ganglia inclusive with the intervening chains. For the upper extremities, the blocking or disconnection of the second and third thoracic ganglia with interruption of the sympathetic chain between the third and fourth ganglia is considered a feasible method of treatment which does not produce the concomitant disability of Horner's syndrome.     

CAUSALGIA—PATHOGENESIS AND TREATMENT

Gross and microscopic anatomical evidence indicates that pain fibers involved in causalgia are those distributed to blood vessels—possibly to the arterioles—and that, for the greater part, these fibers constitute part of the general visceral afferent system.Several investigators have reported evidence that injury to a peripheral nerve of such a type as to cause damage to the vasomotor control of any area produces the initial pain in an extremity, and it is predicated that the arteriolar constriction causing the pain is then prolonged by the sensitization of arteriolar smooth muscle to the amount of epinephrine normally in the blood. If the condition is not treated, tissue anoxia occurs to such an extent that irreversible changes take place in the affected area.Treatment of causalgia in the lower extremities is directed toward interruption of either the vasomotor or afferent supply of blood vessels by blocking or excision of the second to fourth lumbar ganglia inclusive with the intervening chains. For the upper extremities, the blocking or disconnection of the second and third thoracic ganglia with interruption of the sympathetic chain between the third and fourth ganglia is considered a feasible method of treatment which does not produce the concomitant disability of Horner''s syndrome.     

End-stage reflex sympathetic dystrophy

Reflex sympathetic dystrophy is an automatic dysfunction that occasionally complicates healing after trauma or surgery. The syndrome is characterized by pain, swelling, stiffness, and discoloration often out of proportion to the original injury. Early diagnosis and appropriate treatment are the most important factors in the successful outcome of this disabling condition. A case of longstanding, previously untreated reflex sympathetic dystrophy secondary to a minor injury is presented.     

Cold stress alters characteristics of sympathetic nerve discharge bursts.

Frequency-domain analyses were used to determine the effect of cold stress on the relationships between the discharge bursts of sympathetic nerve pairs, sympathetic and aortic depressor nerve pairs, and sympathetic and phrenic nerve pairs in chloralose-anesthetized, baroreceptor-innervated rats. Sympathetic nerve discharge (SND) was recorded from the renal, lumbar, splanchnic, and adrenal nerves during decreases in core body temperature from 38 to 30 degrees C. The following observations were made. 1) Hypothermia produced nonuniform changes in the level of activity in regionally selective sympathetic nerves. Specifically, cold stress increased lumbar and decreased renal SND but did not significantly change the level of activity in splanchnic and adrenal nerves. 2) The cardiac-related pattern of renal, lumbar, and splanchnic SND bursts was transformed to a low-frequency (0-2 Hz) pattern during cooling, despite the presence of pulse-synchronous activity in arterial baroreceptor afferents. 3) Peak coherence values relating the discharges between sympathetic nerve pairs decreased at the cardiac frequency but were unchanged at low frequencies (0-2 Hz), indicating that the sources of low-frequency SND bursts remain prominently coupled during progressive reductions in core body temperature. 4) Coherence of discharge bursts in phrenic and renal sympathetic nerve pairs in the 0- to 2-Hz frequency band increased during mild hypothermia (36 degrees C) but decreased during deep hypothermia (30 degrees C). We conclude that hypothermia profoundly alters the organization of neural circuits involved in regulation of sympathetic nerve outflow to selected regional circulations.     

A search for the factors responsible for absence of recovery of the normal vascular response to oxytocin following sympathetic nerve injury.

In dogs following crush injury to the lumbar sympathetic trunk, reflex vasoconstriction reappears in 4-6 months but the normal vasodilator response to oxytocin does not return even 12 months after crush. Histochemical examination of the walls of the blood vessels shows that division or crush of the lumbar sympathetic trunk or removal of terminal ganglia leads to decentralization, not denervation of the blood vessels. True denervation follows division or crush of the sciatic and femoral nerves. Following recovery from sciatic or femoral crush the pattern of peripheral innervation appears histochemically normal. However, there is no return of the normal vasodilator response to oxytocin. It is concluded that a normal response to oxytocin does not return even after long-term recovery from sympathetic injury, nor does its effect depend on a normal pattern of peripheral adrenergic innervation, but on an unknown more central activity of the sympathetic nervous system.     

Comparison of erector spinae and hamstring muscle activities and lumbar motion during standing knee flexion in subjects with and without lumbar extension rotation syndrome

The aim of this study was to compare the activity of the erector spinae (ES) and hamstring muscles and the amount and onset of lumbar motion during standing knee flexion between individuals with and without lumbar extension rotation syndrome. Sixteen subjects with lumbar extension rotation syndrome (10 males, 6 females) and 14 healthy subjects (8 males, 6 females) participated in this study. During the standing knee flexion, surface electromyography (EMG) was used to measure muscle activity, and surface EMG electrodes were attached to both the ES and hamstring (medial and lateral) muscles. A three-dimensional motion analysis system was used to measure kinematic data of the lumbar spine. An independent-t test was conducted for the statistical analysis. The group suffering from lumbar extension rotation syndrome exhibited asymmetric muscle activation of the ES and decreased hamstring activity. Additionally, the group with lumbar extension rotation syndrome showed greater and earlier lumbar extension and rotation during standing knee flexion compared to the control group. These data suggest that asymmetric ES muscle activation and a greater amount of and earlier lumbar motion in the sagittal and transverse plane during standing knee flexion may be an important factor contributing to low back pain.     

Development of the ascending lumbar and azygos veins in human embryogenesis

The ascending lumbar and azygos veins make a single magistral, but with different topography in the abdominal and thoracic cavities. The former runs more dorsolateral than the sympathetic trunk, and the latter--more ventromedial. These vessels are of different origin in human embryogenesis. The ascending lumbar vein develops from supracardinal veins of the abdominal cavity, that unite the dorsomedial tributaries of the postcardinal vein. The supramesonephral (thoracic) part of the latter makes the azygos vein trunk. Its beginning in the form of a plexus is determined by anastomosing supracardinal, postcardinal and mesocardinal veins. The mesocardinal vein serves as a longitudinal anastomosis for veins, connecting medial tributaries of the postcardinal vein. Differential peculiarities of its basin over the whole length and topographic peculiarities of the ascending lumbar and azygos veins depend on growth specificity of kidneys and adrenals, as well as on other organs in human embryogenesis.     

Pain due to lesions of central nervous system removed by sympathetic block.

Eight patients were studied in whom a lesion within the central nervous system caused constant pain and hyperpathia. Blockade of the sympathetic supply to the periphery was carried out in each patient by stellate ganglion block or intravenous infusion of guanethidine 15 mg in 30 ml saline into a limb on the affected side. On almost every occasion the pain and hypersensitivity were reduced, sometimes completely. Thus chronic pain and hyperpathia arising from a lesion in the central nervous system may be abolished by blocking the sympathetic supply to the periphery; this effect may be achieved when not all the peripheral nerves of the affected region have had their sympathetic nerve supply blocked. Such blockade may be worth repeating in the hope of achieving lasting relief of the intractable pain.     

Reflex sympathetic dystrophy syndrome: consensus report of an ad hoc committee of the American Association for Hand Surgery on the definition of reflex sympathetic dystrophy syndrome

This report proposes that reflex sympathetic dystrophy be defined as a pain syndrome in which the pain is accompanied by loss of function and evidence of autonomic dysfunction. In the clinical setting, this diagnosis is usually associated with other anatomic and psychological diagnoses and may be associated with a variety of systemic illnesses and medicolegal factors. All components should be assessed before a treatment plan is established. Priorities should go to emergency care, acute injuries, and systemic illness, psychiatric problems, and chronic anatomic problems, in that order. Early, accurate diagnosis improves prognosis.     

NEWER METHODS FOR SELECTION OF PATIENTS FOR LUMBAR SYMPATHECTOMY

The degree of vasodilatation achieved by various diagnostic methods (arterial occlusion, ganglionic block established by certain agents, lumbar sympathetic block, spinal anesthesia, and indirect heating) was studied by means of the pneumo-plethysmogram as well as through readings of skin temperature and skin resistance. The data obtained were interpreted as to their value in determining the type of patient with vascular disease for whom lumbar sympathectomy would be of noticeable benefit. Arterial occlusion proved itself a rapid and simple method which in most patients produced satisfactory results. As a rule, lumbar sympathectomy was effective in patients who preoperatively had shown a positive response upon release of arterial occlusion. A negative response, that is, absence of significant increase in blood flow, does not necessarily indicate organic disease, and cannot be taken to mean that lumbar sympathectomy would always be ineffective. Ganglionic block, using 2.6 dimethyl piperidinium bromide or tetraethylammonium ion, was generally less reliable in indicating the probable results of sympathectomy than lumbar sympathetic block or indirect heating. Lumbar sympathetic block with procaine was followed by a greater increase in skin temperature and blood flow than spinal anesthesia, and permitted far more accurate conclusions as to the probable outcome of sympathectomy. Subsequent to indirect heating the plethysmogram showed characteristic differences depending on the degree of vascular disease present. From the effect of this simple, safe and painless method upon the relative blood flow to the toe it becomes possible to arrive at a comparatively accurate estimate of the clinical benefit to be expected from lumbar sympathectomy.     

The use of sensory-sympathetic coupling indices for diagnosing of sympathetically maintained pain with laser Doppler flowmetry

For the first time the objective diagnosis of sympathetically maintained pain was created with laser Doppler flowmetry (LDF), directed specially to discovery of skin sensory-sympathetic coupling at 49 patients with posttraumatic complex regional pain syndrome. Sensory-sympathetic coupling was diagnosed as combination of sympathetic vasomotor activity with the existence of sensory peptidergic blood flow oscillations in frequency range of 0.047-0.069 Hz in LDF wavelet-spectrum. The results of LDF diagnosis were compared with clinical evaluation of sympathetically maintained pain carried out after desympathization surgery (thoracoscopic clipping above and below the Th3 ganglion of sympathetic chain at 33 patients and perivascular sympathectomy at the level of brachial artery and veins at 16 patients). Sensitivity of preoperative LDF-diagnosis was 90.2%, specificity--87.5%, positive predictive value--97.3%, negative predictive value--63.6%, diagnostic effectiveness--89.8%.     

Changes in the blood vessels of the spinal cord and spinal ganglia following chronic stimulation of the lumbar regions of the sympathetic trunks and gangliosympathectomy

Morphological studies in 40 rabbits demonstrated that chronic irritation of the lumbar sympathetic trunks resulted in more pronounced architectonic changes, in vessel walls and in neurons of the lumbar sympathetic ganglia in 15 days than did the bilateral lumbar gangliosympathectomy at the same time. In both series of experiments more prominent changes were noticed in the spinal ganglia than in the spinal cord, that could be explained by different degree of lesions in the nerves supplying them and by organic specification of their angioarchitectonics. The data obtained made it possible to include novocain block (anesthesia) into complex therapy to manage spinal apoplexy in clinic.     

Strain-gauge plethysmography in the evaluation of the evolution of deep vein thrombosis of the legs

Previous research has shown that MVO (Maximum Venous Outflow), VR (Venous Reflux), VE (Venous Emptying) and the respiratory waves recording are useful in differentiating occlusion and recanalization in postphlebitic syndrome. In the present work strain-gauge plethysmography was employed to quantitate the venous function after deep venous thrombosis of the legs. The studies were performed in a vascular laboratory with controlled temperature (23 to 25 C); records were obtained by a plethysmograph Parks mod. 270 connected to a Hewlett-Packard multi-channel mod. 7700. 17 patients (12 males, 5 females), mean age 55 years (range 24-75) that presented femoropopliteal thrombophlebitis documented by phlebography at the admission to the hospital were examined. MVO with and without superficial veins occlusion was measured by a mercury in silastic strain-gauge placed circumferentially about the calf. A pneumatic cuff thigh was inflated to 60 mm Hg. VE was measured in patients lying in inclined bed with the lower extremities 100 cm below the heart level compressing the calf with a pneumatic cuff 10 times for 5 seconds; the strain-gauge was placed on the foot level. VR after Valsalva's maneuver and the respiratory waves were recorded by a strain-gauge positioned at the maximum girth about the calf in patients lying on inclinated bed with the lower extremities 50 cm below the heart level. The result are here indicated: (Table: see text) There was differences in the evolution of venous function after deep venous thrombosis of the legs for each patient. Strain-gauge plethysmography may become evaluable non invasive technique in the evaluation of deep venous thrombosis evolution in the legs. The therapeutic assessment of postphlebitic syndrome.     

Conducting pathways of the rabbit lumbar sympathetic ganglia

Conducting pathways of ganglia from the lumbar portion (L₃–L₅) of the sympathetic trunk in rabbits were studied by recording action potentials from nerves of the ganglia evoked by stimulation of other nerves of these ganglia, and by intracellular recording from single neurons. Besides the well-known system of descending preganglionic fibers, which enter the trunk through white rami communicantes and, as they pass through the ganglia, form synapses on ganglionic neurons, some preganglionic fibers were shown to enter the sympathetic chain through gray rami communicantes and to run in both ascending and descending directions, forming synaptic connections with neurons of the lumbar ganglia.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 16, No. 2, pp. 247–254, March–April, 1984.     

Differentiated pressor and sympathetic responses to dual brain stimulation: ventromedial hypothalamus versus locus coeruleus

Sensitivity of the ventromedial hypothalamus (VMH) to electrical stimulation was compared with that of the locus coeruleus (LC) in urethane-anesthetized rats. Based not only on current strengths required to elicit threshold effects, but also on magnitude of pressor responses to suprathreshold stimulation, the LC was consistently more sensitive than the VMH. Despite this greater pressor sensitivity, splanchnic nerve firing increased almost equally upon stimulation of either brain area. Similar comparisons made in other rats following bilateral adrenalectomy or pretreatment with a vasopressin antagonist showed no significant alteration of pressor and sympathetic responsiveness to stimulation of either the LC or the VMH. When frequency of neural firing was recorded from a lumbar sympathetic trunk instead of the splanchnic nerve, increases in sympathetic nerve activity produced by LC stimulation were significantly larger than those produced from the VMH. The results suggest that greater pressor sensitivity of the LC is due, at least in part, to stronger constriction in vascular beds innervated by the lumbar sympathetic chains.     

Autonomic control after blockade of the norepinephrine transporter: a model of orthostatic intolerance.

Orthostatic intolerance is a debilitating syndrome characterized by tachycardia on assumption of upright posture. The norepinephrine (NE) transporter (NET) has been implicated in a genetic form of the disorder. We assessed the combined central and peripheral effects of pharmacological NET blockade on cardiovascular regulation and baroreflex sensitivity in rats. NE reuptake was blocked chronically in female Sprague-Dawley rats by the NET antagonist desipramine (DMI). Treated animals demonstrated an elevated supine heart rate, reduced tyramine responsiveness, and a reduced plasma ratio of the intraneuronal NE metabolite dihydroxyphenylglycol relative to NE, all of which are consistent with observations in human NET deficiency. Spectral analysis revealed a dramatic decrease in low-frequency spectral power after DMI that was consistent with decreased sympathetic outflow. Stimulation of the baroreflex with the vasodilator nitroprusside revealed an attenuated tachycardia in DMI-treated animals. This indicated that the DMI-induced sympathoinhibitory effects of increased NE in the brain stem predominates over the functional elevation of NE stimulation of peripheral targets. Thus attenuated baroreflex function and reduced sympathetic outflow may contribute to the orthostatic intolerance of severe NET deficiency.     

Use of sensory-sympathetic coupling indices for diagnosing sympathetically maintained pain with laser Doppler flowmetry

The first objective diagnosis of sympathetically maintained forms of pain employing laser Doppler flowmetry (LDF) and specifically targeted at detecting sensory-sympathetic coupling in the skin has been developed and tested in 49 patients with the posttraumatic complex regional pain syndrome. Sensory-sympathetic coupling was diagnosed as a combination of sympathetic vasomotor activity and the presence of sensory peptidergic blood flow oscillations in a frequency band of 0.047–0.069 Hz in the LDF wavelet spectrum. The results of the LDF diagnosis were compared with the clinical evaluation of sympathetically maintained pain carried out after desympathization surgery (thoracoscopic clipping above and below the Th3 ganglion of the sympathetic chain in 33 patients and perivascular sympathectomy at the level of the brachial vascular bundle in 16 patients). The sensitivity of preoperative LDF diagnosis was 90.2%; the specificity was 87.5%; the positive predictive value was 97.3%; the negative predictive value was 63.6%; and the diagnostic efficiency was 89.8%.