Effects Of Dorsal Rhizotomy Research Articles

Dorsal Rhizotomy for Pain from Neoplastic Lumbosacral Plexopathy in Advanced Pelvic Cancer

Background: Pain from neoplastic lumbosacral plexopathy is resistant to conventional pain treatment. According to a recent review of destructive procedures for cancer pain, only cordotomy has been reported to play an important role in the treatment of cancer pain. To date, the effectiveness of dorsal rhizotomy, which selectively interrupts pain transmission, has not been shown in neoplastic lumbosacral plexopathy. Objectives: The present study seeks to find out the effectiveness of selective dorsal rhizotomies for intractable pain from neoplastic lumbosacral plexopathy in terminal pelvic cancer patients. Methods: Dorsal rhizotomies of the involved segments were performed on 6 cancer patients in whom neuropathic pain from lumbosacral plexus involvement in terminal pelvic cancer had been refractory to other therapies. Clinical efficacy of the procedure was assessed by comparing patient pain ratings and narcotic usage before and after dorsal rhizotomy. Results: Examination of the results indicated a significant reduction in pain ratings as well as a significant reduction in daily narcotic use. No adverse neurological effects were observed and no recurrence of pain from neoplastic lumbosacral plexopathy was noted. Conclusions: These findings provide corroborating clinical evidence for the effectiveness of selective dorsal root rhizotomy for the intractable pain from lumbosacral plexopathy in terminal pelvic cancer patients.

Retrograde signaling does not mediate sodium excretion during dorsal column stimulation

Prior work found an increase in renal sodium excretion in male spontaneously hypertensive rats (SHR) following dorsal spinal column stimulation (DCS) at the spinal segment of the left renal sensory nerves (T12–T13). General sympathetic tone, and renal blood flow were unaltered by DCS. The effects of dorsal rhizotomy on the DCS‐induced renal sodium excretion was investigated in male SHR. SHR were randomly assigned to one of the following groups: no‐stimulation (NS), stimulation (S), no stimulation + Rhizotomy (NS+R), and Stimulation + Rhizotomy (S+R). Stimulated rats received DCS during the 2nd of five 15‐min. collection periods. Blood pressure was measured via a carotid artery cannula, and urine was collected via a bladder cannula. A standard stimulation parameter of 66% of the motor threshold (0.2 msec duration and 50 Hz) was used. Urine sodium was analyzed using flame photometry. Sodium excretion was significantly elevated in periods 3 and 4 in the S group when compared with corresponding periods in the NS group. Sodium excretion was significantly elevated in period 5 in the S+R group when compared with the NS+R. There were no differences between the S+R and the S groups. The DSC‐induced increase in sodium excretion is independent of retrograde signaling in the renal nerves. This research was funded by a departmental grant, in the Department of the Biological Sciences, Minnesota State University, Mankato, MN

Nitric oxide synthase neurons in the rodent spinal cord: distribution, relation to Substance P fibers, and effects of dorsal rhizotomy

The indirect immunofluorescent method was employed to investigate the distribution of neuronal nitric oxide synthase-like immunoreactivity(nNOS-LI) in the spinal cord of the golden hamster and to compare it to data obtained from rats. Immunoreactive neurons were found throughout the cervico-sacral extent in the dorsal horn (mainly in laminae I–III) and in the preganglionic autonomic regions, i.e., the sympathetic intermediolateral nucleus (IML), lateral funicle (LF), intercalated region (IC), the area surrounding the central canal (CA), and the sacral preganglionic parasympathetic cell group. While the distribution of immunoreactive cells was generally similar in both species, some differences were observed. For example in the hamster LF, a higher percentage of stained neurons was seen than in the IML, while the situation was rather inverse in the rat. In order to study the coincidence of nNOS-LI in the population of preganglionic sympathetic neurons (PSN) that innervate the superior cervical ganglion (SCG), these were identified by retrograde axonal transport of fluoro-gold (FG) following unilateral injection into the SCG. PSN were localized ipsilateral to the injection site mainly in the IML and LF of spinal segments C7–Th4. The portion of double-labeled neurons of the IML were lower in hamster (17% in C7, 34% in C8) of FG-labeled cells) than in rat (47% in C8, 77% in Th2), while in the LF of segments C8–Th2 in both species the majority of FG-neurons contained nNOS. While only very few double-labeled neurons were detected in the IC in hamster and rat, a striking difference was observed in the CA, where no double-labeled neurons were found in hamster, but up to 50% in rat. Double immunofluorescence detection of nNOS and substance P (SP) showed that in both the autonomic regions and the dorsal horn, SP-LI fibers and puncta were present in close spatial relationship to nNOS-LI cell bodies. These results were basically identical in the hamster and rat. Unilateral transection of the dorsal roots of segments C6–Th2 in rats resulted in a clear reduction of SP-LI structures in the dorsal horn 5 days after rhizotomy, but not in the autonomic regions. Compared to the unlesioned side, the numbers of nNOS-LI neurons in the superficial laminae of the dorsal horn were reduced to 32–46% in the lesioned segments, and to 53% and 87%, respectively, in the two segments cranial to the rhizotomized segments but remained unchanged caudally to the lesion. Numbers of nNOS-LI cell bodies in the autonomic regions were not altered following dorsal root transection. The present study provides data on the widespread distribution of nNOS in the spinal cord of golden hamster and describes the partial coincidence of the enzyme in PSN. The effects of dorsal rhizotomy on nNOS-LI neurons in the dorsal horn reveal that primary-afferent fibers provide a stimulatory influence on neurons of the dorsal horn to generate the gaseous neuroactive substance, nitric oxide.

Extrinsic Innervation of the Cat Prostate Gland: A Combined Tracing and Immunohistochemical Study

The purpose of the present study was to determine the peripheral neural pathways, spinal distribution, sizes, and peptide transmitter content of primary afferent and autonomic efferent neurons that innervate the prostate gland. Retrograde transport of the fluorescent dye "fast blue" (injected into the prostate gland) was combined with neurotransmitter immunohistochemistry. Lesions of the pelvic and pudendal nerve were used to determine the peripheral neural pathways. The majority of the afferent innervation arose from the sacral dorsal root ganglia (DRG) and was equally comprised of small, substance P- and calcitonin gene-related peptide-immunoreactive (IR) neurons and large, non-IR neurons. The majority (70%) of the afferent axons traversed the pelvic nerve with the remainder traversing the pudendal nerve. Fewer afferent neurons were located in lumbar DRG; nearly all of these were small, peptidergic neurons. Efferent autonomic neurons were located in the inferior mesenteric ganglia (IMG), sympathetic chain ganglia (SCG), and pelvic plexus ganglia (PPG). Nearly all efferent neurons in the IMG and SCG, but only 2/3 of the PPG neurons, contained dopamine-beta-hydroxylase. Substantial neuropeptide Y innervation was derived from the SCG but not the IMG or PPG. First, clinical reports suggested that sensory innervation of the prostate would be purely nociceptive in nature (implied by small, peptide-IR neurons). However, the present study suggests that there may also be a substantial, presumably non-nociceptive, afferent innervation (implied by findings of large, non-IR neurons). Second, 3 sources of autonomic efferent innervation exist, each being different in the distribution of transmitter phenotypes. Understanding the physiological role of putative non-nociceptive primary afferent neurons, and the differential roles of the various autonomic neurons, is likely to be important in developing therapies for the treatment of prostatic diseases, such as benign prostatic hyperplasia and prostatodynia.

Distribution of neuropeptide FF (FLFQPQRFamide) receptors in the adult rat spinal cord: effects of dorsal rhizotomy and neonatal capsaicin

By using quantitative autoradiography and highly selective iodinated ligands, we quantified modifications in neuropeptide FF binding sites in the superficial layers (laminae I and II) of the cervical (C6-C8 segments) and lumbar (L3-L5 segments) enlargements in two models: (i) rats neonatally treated with capsaicin; (ii) rat submitted 15 days before to unilateral dorsal rhizotomies. We comparatively analysed the distribution of mu-opioid binding sites in the same animals. We have shown that the [125I]YLFQPQRFamide (neuropeptide FF sites) labelling is not significantly modified following selective damage of fine afferent fibres by neonatal capsaicin treatment. In the cervical and lumbar enlargements, capsaicin-treated/control binding ratios for [125I]YLFQPQRFamide were 0.90 and 0.86, respectively. While unilateral dorsal rhizotomy induced a drastic decrease in [125I]FK-33-824 labelling in the side ipsilateral to the lesion as compared to the intact side of (yielding ratios of 0.29 and 0.31 for cervical and lumbar levels, respectively), [125I]YLFQPQRFamide labelling was not significantly modified, yielding ratios of 0.98 and 0.91 for cervical and lumbar levels, respectively. These data suggest that, in contrast with a majority of mu-opioid receptors, neuropeptide FF receptors are not located on fine primary afferent fibers carrying nociceptive information from the fore- or hindlimb in the rat. This preferential postsynaptic localization, together with the reported "morphine modulating" action of this peptide, support the proposal of a role for neuropeptide FF in intraspinal modulation of nociceptive input.

Effects of dorsal rhizotomy and selective lesion of serotonergic and noradrenergic systems on 5-HT1A, 5-HT1B, and 5-HT3 receptors in the rat spinal cord.

Autoradiographic studies were performed in combination with dorsal rhizotomy or selective lesion of descending serotonergic or noradrenergic systems in an attempt to identify the neuronal cell types endowed with the serotonin 5-HT1A, 5-HT1B and 5-HT3 receptors in the rat spinal cord. Unilateral sectioning of seven dorsal roots (C4-T2) at the cervical level produced a marked decrease (approximately-75%, 10 days after the surgery) in the binding of [125I]iodozacopride to 5-HT3 receptors in the superficial layers of the ipsilateral dorsal horn, further confirming the preferential location of these receptors on primary afferent fibres. In addition, a significant decrease (approximately 20%) in the binding of [3H]8-OH-DPAT to 5-HT1A receptors and of [125I]GTI to 5-HT1B receptors was also observed in the same spinal area in rhizotomized rats, suggesting that a small proportion of these receptors are also located on primary afferent fibres. The labelling of 5-HT1B receptors was significantly decreased (-12%) in the dorsal horn at the cervical (but not the lumbar) level, and that of 5-HT3 receptors was unchanged in the whole spinal cord in rats whose descending serotonergic projections had been destroyed by 5,7-dihydroxytryptamine. Conversely, the labelling of 5-HT1A receptors was significantly increased in the cervical (+13%) and lumbar (+42%) dorsal horn in 5,7-dihydroxytryptamine-lesioned rats. Similarly, [3H]8-OH-DPAT binding to 5-HT1A receptors significantly increased (+26%) in the lumbar (but not the cervical) dorsal horn in rats whose noradrenergic systems had been lesioned by DSP-4. The labelling of 5-HT1B receptors was also increased (+31% at the cervical level; +17% at the lumbar level), whereas that of 5-HT3 receptors remained unchanged in these animals. These data indicate that complex adaptive changes in the expression of 5-HT1A and 5-HT1B receptors occurred in the rat spinal cord following the lesion of descending monoaminergic systems.

Effects of dorsal rhizotomy on depressor response to spinal cord stimulation mediated by endogenous calcitonin gene-related peptide in the pithed rat

The effects of acute and chronic dorsal rhizotomy on vasodilation induced by spinal cord stimulation were investigated in the pithed rat in vivo. Pithed rats were treated intravenously with hexamethonium (2 mg/kg/min) to block autonomic outflow, and mean arterial blood pressure was maintained at approximately 100 mm Hg with methoxamine (10 to 15 micrograms/kg/min). Electrical stimulation (2 or 4 Hz, 10 V, 1 msec) of the lower thoracic spinal cord (T9-12) via the pithing rod caused a frequency-dependent depressor response without a change in heart rate. The depressor response to spinal cord stimulation was inhibited by the intravenous administration of human calcitonin gene-related peptide (CGRP) [8-37] (60 nmol/kg/min) or tetrodotoxin (100 micrograms/kg). In the pithed rat with acute or chronic bilateral dorsal root rhizotomy at lower thoracic levels (T8-12), spinal cord stimulation at 2 and 4 Hz caused no depressor response. These results suggest that the depressor response to spinal cord stimulation is mediated by endogenous CGRP, which is released from CGRP-containing nerves. The present results also suggest an outflow of CGRP-containing nerves from the spinal cord via the dorsal roots.

CGRP-immunoreactive primary afferent nerve fibers in the rat urinary bladder: Effects of dorsal rhizotomy and MK-801

A transection lesion of the suprasacral spinal cord results in a decreased density of calcitonin gene-related peptide (CGRP)-immunoreactive (I) primary afferent nerve fibers in the rat urinary bladder. The fiber density can be restored by postsurgical treatment with the N-methyl- d-aspartate receptor antagonist MK-801. We are attempting to determine the level of the primary afferent neuron at which MK-801 might have a restorative effect on CGRP immunostaining. Thus, the purpose of this study was to determine if MK-801 had a similar restorative effect on immunostaining for CGRP in bladder nerves after a direct lesion of the sacral afferent system, i.e., rhizotomy of the L 6 and S 1 dorsal roots. To assess the effect of the lesion, the mean length and number of bladder CGRP-I nerve fibers, as well as the number of CGRP-I perikarya in the L 6 and S 1 dorsal root ganglia (DRG), were measured following bilateral L 6 and S 1 dorsal rhizotomies. Both the mean length and the numbers of CGRP-I bladder fibers were significantly decreased by the lesion. However, the number of CGRP-I primary afferent perikarya in the L 6 and S 1 DRG was unchanged from control values. Rats which received rhizotomies and subsequent treatment with MK-801 did not exhibit restoration of the density of CGRP-I bladder fibers nor an alteration in the number of CGRP-I primary afferent perikarya. These data suggest that MK-801-induced restoration of bladder CGRP-I primary afferent nerve fibers may rely on an intact central process.

Effects of dorsal rhizotomy on neurokinin receptor sub-types in the rat spinal cord: a quantitative autoradiographic study

Although abundant evidence suggests a major role for substance P (SP) and other neurokins (NK) in the transmission of nociceptive information, it is not known whether the various NK receptor classes are differentially located in the substantia located in the substantia gelatinosa of the spinal cord where primary afferent fibres mostly terminate. In order to investigate this issue, we studied the effects of unilateral dorsal rhizotomy on binding of 125I-Bolton-Hunter-SP, (2-[ 125I]iodohistidyl 1)-neurokinin A, and 125I-Bolton-Hunter-eledoisin as respective radioligands for the NK-1, NK-2 and NK-3 receptor sub-types. Seven, 14, 21 and 28 days following unilateral lumbosacral dorsal horn deafferentation, NK receptor binding parameters were evaluated using quantitative receptor autoradiography. Rhizotomy produced an increase in the densities of NK-1, NK-2 and NK-3 binding sites in the superficial laminae of the dorsal horn. Increases were maximal at 14 days, post-operatively, for both NK-1 and NK-2 sites; slight recovery being observed thereafter. For NK-3 sites, unilateral rhizotomy induced a progressive increase in binding without evidence of recovery over time, at least up to 28 days post-lesion. NK-1 receptor binding parameters around the central canal and in the ventral horn were not affected by the dorsal rhizotomy. These data suggest that all 3 NK receptor classes are located post-synaptically to afferent fiber terminals in laminae I, II and X of the dorsal horn of the spinal cord.

The effects of dorsal rhizotomy and spinal cord isolation on calcitonin gene-related peptide-labeled terminals in the rat lumbar dorsal horn

In the present study, the origin of calcitonin gene-related peptide (CGRP) to the dorsal horn in the rat lumbar spinal cord is investigated. CGRP immunoreactivity is examined following multiple unilateral and bilateral dorsal rhizotomies and isolated cord preparations (spinal cords are isolated by transecting the cord in two places and cutting all dorsal roots between the transections). Seven to 11 days after surgery, unilateral multiple dorsal rhizotomies result in a drastic decrease in CGRP-stained terminals on the operated side; following bilateral dorsal rhizotomies and isolated cord preparations, one or two CGRP varicosities remain in the dorsal horn in each section. The numbers of CGRP-immunostained varicosities observed in the latter two preparations are not significantly different, suggesting that few if any axons descending from the brain contribute to the CGRP terminal population in the spinal cord dorsal horn. Based on these data, we hypothesize that dorsal root ganglion cells are the only source of CGRP to the rat lumbar dorsal horn.

Morphology of HRP-injected spinocervical tract neurons: effect of dorsal rhizotomy

Twenty-five physiologically identified spinocervical tract (SCT) neurons in the sixth lumbar segment of the cat were filled with HRP by intracellular injection. All were reconstructed from sagittal sections using the camera lucida, and a subset (n = 18) was also reconstructed using a computer reconstruction system. Thirteen cells were in intact preparations, nine were in spared root preparations (L5, L6, S1, S2 cut; L7 spared), and three were in preparations with L5 through S2 cut. Analysis of the dendritic tree of these neurons revealed little change in gross morphology after partial deafferentation despite increased proportions sensitive to nociceptive input (Sedivec et al., 1983). The dendrites still largely respected the lamina II-III border, and relatively few dendrites were directed ventrally from the cell body, although the ratio of ventral to dorsal dendrites was greater than normal. The major change was an increase in surface area and volume caused by changes in diameter (but not length) of the dendrites. Larger-than-usual maximum branch order of individual dendritic trees of some cells was also observed after chronic deafferentation. Thus, SCT cells in deafferented segments do not undergo atrophy, but show, rather, limited signs of growth and the possibility of dendritic reorganization. We have also computed correlations between different parameters of these cells (cell body size, number and size of primary dendrites, total area and length of individual dendrites) and have found that, as in motoneurons, diameter of the primary dendrite measured 30 micron from the soma is significantly correlated with total dendritic surface area and length. SCT neurons tend to have more dendrites than spinal alpha-motoneurons, but total surface area is smaller for a given diameter of a proximal dendrite.

Morphology of HRP-injected spinocervical tract neurons: effect of dorsal rhizotomy

Morphology of HRP-injected spinocervical tract neurons: effect of dorsal rhizotomy

Effects of dorsal rhizotomy on the several types of primary afferent terminals in laminae I-III of the rat spinal cord. An electron microscope study.

After cervical dorsal rhizotomy, small dark central terminals (C1) of glomeruli underwent electron dense changes at 8 h and were all degenerated at 36 h; their number persisted, though slightly diminished, up to 15 days, glial engulfment being negligible. Light large central terminals without neurofilaments (CIIa) showed electron-lucent or electron-dense degeneration from 14 to 36 h, while those with neurofilaments (CIIb) exhibited increased neurofilamentous areas, with depletion and presynaptic concentration of synaptic vesicles as in the electron-lucent change, at the 8-36 h postrhizotomy periods. Both CII-varieties were all degenerated at 36 h and became electron dense at 48 h; glial phagocytosis was intense and no terminals were present after 4 days. It is concluded that in the rat the 3 types of central glomerular terminals are primary axons, and that each type undergoes a different pattern of degeneration which points to a separate primary afferent origin. Numerous nonglomerular axodendritic endings began showing electron-dense degeneration at 8 h which rapidly masked their normal structure, although most appeared to contain round agranular vesicles, and some of them dense-cored vesicles (in lamina I). A few endings exhibited electron-lucent degeneration. Labeling methods seem preferable for studying the primary origin of nonglomerular terminals, due to the difficulty in recognizing the normal predegenerative structure of these profiles.

Effect of dorsal rhizotomy on the autoradiographic distribution of opiate and neurotensin receptors and neurotensin-like immunoreactivity within the rat spinal cord

The distributions of neurotensin and opiate receptors within the dorsal horn of the rat spinal cord were studied with quantitative autoradiographic techniques and compared with the immunohistochemical localizations of neurotensin and methionine-enkephalin-like immunoreactivity in this region. High densities of both neurotensin and opiate receptors were found within the superficial layers of the spinal cord, paralleling the distribution of neurotensin and enkephalin-containing interneurons and nerve terminals. Dorsal root section produced a 40% loss of opiate receptors throughout layers I and II of the spinal cord whilst no change in neurotensin receptor density or distribution was found. At the electron microscopic level the presence of neurotensin-like immunoreactivity within vesicle-containing profiles in the dorsal horn was demonstrated; however, no interaction of these terminals with primary afferent boutons was seen.

Effect of dorsal rhizotomy on postural tremor in the monkey.

Rhizotomy of the dorsal roots of the upper limb in lesioned monkeys with lesioned-induced and harmaline-induced tremor caused complete anaesthesia and akinesia of the corresponding limb, which only showed purposeless movements. The rate and rhythm of postural tremor and the reciprocality of the bursts in opposite muscles were not affected by the rhizotomy; the incidence of tremor episodes was greater in some animals. Rhizotomy apparently interfered with the amplitude of the bursts which, at times, was less regular in the deafferented limb. In four out of six animals the rhizotomy involved the blood supply of the dorsal part of the lateral column. This caused a degeneration of the corresponding lateral corticospinal and dorsal spinocerebellar tracts, producing a weakness of the ipsilateral lower limb which gradually improved. Faster bursts (12–13/sec) were also noted on the EMG in response to harmaline in monkeys with cerebellar lesions. These findings suggest that the influence transmitted through the spinal dorsal roots does not play an important role in initiating postural tremor. The rate and rhythm of tremor episodes are uninfluenced by impulses transmitted through the dorsal roots which, however, apparently exert a stabilizing effect on the amplitude of the bursts.

Effects of dorsal rhizotomy upon subthalamic dyskinesia in the monkey.

ONE UNRESOLVED question concerning various forms of dyskinesia is the role that sensory input plays in the underlying basic neural mechanism. Relatively little data are available concerning the effects of dorsal rhizotomies upon human dyskinesia mainly because this procedure would have to be extensive and would result in widespread sensory loss. In the human, dorsal rhizotomy has been performed primarily for relief of pain, visceral crises, and spasticity or rigidity.^{10,13,15,16,18,33}There are, however, a few instances in which dorsal rhizotomies have been performed upon patients with dyskinesia. According to Frazier,¹⁵surgical section of successive cervical dorsal roots in a patient with infantile diplegia caused spasticity to be diminished and all athetoid movements to disappear. A similar result was reported by Clark and Taylor¹⁰but all spasticity was abolished in this case. Foerster,¹³whose extensive experience with dorsal rhizotomy is well known, summarized his views on resection