Dorsal Root Rhizotomy Research Articles

Spinal Reflex Recovery after Dorsal Rhizotomy and Repair with Platelet-Rich Plasma (PRP) Gel Combined with Bioengineered Human Embryonic Stem Cells (hESCs).

Dorsal root rhizotomy (DRZ) is currently considered an untreatable injury, resulting in the loss of sensitive function and usually leading to neuropathic pain. In this context, we recently proposed a new surgical approach to treat DRZ that uses platelet-rich plasma (PRP) gel to restore the spinal reflex. Success was correlated with the reentry of primary afferents into the spinal cord. Here, aiming to enhance previous results, cell therapy with bioengineered human embryonic stem cells (hESCs) to overexpress fibroblast growth factor 2 (FGF2) was combined with PRP. For these experiments, adult female rats were submitted to a unilateral rhizotomy of the lumbar spinal dorsal roots, which was followed by root repair with PRP gel with or without bioengineered hESCs. One week after DRZ, the spinal cords were processed to evaluate changes in the glial response (GFAP and Iba-1) and excitatory synaptic circuits (VGLUT1) by immunofluorescence. Eight weeks postsurgery, the lumbar intumescences were processed for analysis of the repaired microenvironment by transmission electron microscopy. Spinal reflex recovery was evaluated by the electronic Von Frey method for eight weeks. The transcript levels for human FGF2 were over 37-fold higher in the induced hESCs than in the noninduced and the wildtype counterparts. Altogether, the results indicate that the combination of hESCs with PRP gel promoted substantial and prominent axonal regeneration processes after DRZ. Thus, the repair of dorsal roots, if done appropriately, may be considered an approach to regain sensory-motor function after dorsal root axotomy.

<p>G Protein-Gated Inwardly Rectifying Potassium Channel Subunit 3 is Upregulated in Rat DRGs and Spinal Cord After Peripheral Nerve Injury</p>

BackgroundG protein-gated inwardly rectifying potassium (GIRK) channels are involved in the regulation of neuronal excitability. Four GIRK subunits (GIRK1-4) are expressed in rat dorsal root ganglia (DRGs). Recently, we have characterized the expression of GIRK1 and −2, and both are downregulated in rat DRGs and spinal cord after a complete sciatic nerve transection (axotomy). Here, we aimed to study the neurochemical characteristics of GIRK3, and its regulation in rat DRGs and spinal cord induced by nerve injury.MethodsA sciatic nerve axotomy was performed to study the influences of injury on GIRK3 expression in DRGs and spinal cord. A dorsal root rhizotomy and a sciatic nerve crush were employed to study the axonal transport of GIRK3 protein, respectively. Immunohistochemistry analysis was employed for investigating the neurochemical characteristics of GIRK3.ResultsIn control DRGs, ~18% of neuron profiles (NPs) were GIRK3-positive (+), and ~41%, ~48% and ~45% of GIRK3+ NPs were CGRP+, IB4+ and NF200+, respectively. GIRK3-like immunoreactivity was observed in glabrous skin of hind paws and axons originating from DRG neurons. Fourteen days after axotomy, more than one-third of DRG NPs were GIRK3+, and among these ~51% and ~56% coexpressed galanin and neuropeptide Y, respectively. In control animals, a small group of interneurons found in the dorsal horn was GIRK3+. In addition, GIRK3+ processes could be observed in superficial laminae of spinal dorsal horn. After nerve injury, the intensity of GIRK3-like immunoreactivity in the superficial layers was increased. Evidence based on rhizotomy and sciatic nerve crush indicated both anterograde and retrograde transport of GIRK3.ConclusionOur study demonstrates that GIRK3 is expressed in sensory neurons and spinal cord. GIRK3 has both anterograde and retrograde axonal transport. GIRK3 expression can be regulated by peripheral nerve injury.

Reflex arc recovery after spinal cord dorsal root repair with platelet rich plasma (PRP)

Spinal dorsal roots can be affected by a wide range of lesions, leading to a significant loss of proprioceptive information transmission and greatly affecting motor behavior. In this context, the reimplantation of lesioned roots with platelet-rich plasma (PRP) may allow nerve regeneration. Therefore, the present study evaluated sensorimotor improvement following dorsal root rhizotomy and repair with PRP. For this purpose, female Lewis rats were subjected to unilateral rhizotomy (RZ) of the L4–L6 dorsal roots and divided into the following groups: (1) the unlesioned control group; (2) the group that underwent rhizotomy (RZ) without repair; and (3) the group that underwent RZ followed by root repair with PRP. PRP was obtained from human blood and characterized regarding platelet concentration, integrity, and viability. Reflex arc recovery was evaluated weekly for eight weeks by the electronic von Frey method. The spinal cords were processed 1 week postlesion to evaluate the in vivo gene expression of TNFα, TGF-β, BDNF, GDNF, VEGF, NGF, IL-4, IL-6, IL-13 by qRT-PCR and eight weeks postlesion to evaluate changes in the glial response (GFAP and Iba-1) and excitatory synaptic circuits (VGLUT1) by immunofluorescence. The results indicated that PRP therapy partially restores the paw withdrawal reflex over time, indicating the reentry of primary afferents from the dorsal root ganglia into the spinal cord without exacerbating glial reactivity. Additionally, the analysis of mRNA levels showed that PRP therapy has immunomodulatory properties. Overall, the present data suggest that the repair of dorsal roots with PRP may be considered a promising approach to improve sensorimotor recovery following dorsal rhizotomy.

351 Long-term Functional Outcome Following Selective Dorsal Root Rhizotomy for Spastic Cerebral Palsy A Natural History-Matched Prospective Cohort With 15-Year Follow-up

351 Long-term Functional Outcome Following Selective Dorsal Root Rhizotomy for Spastic Cerebral Palsy A Natural History-Matched Prospective Cohort With 15-Year Follow-up

Phrenic afferent stimulation modulates cardiorespiratory output in the adult rat

Anatomical work from our laboratory indicates that small and large diameter phrenic nerve afferent fibers localize to the dorsal laminae, project throughout the ipsilateral spinal gray matter and occasionally reach the contralateral dorsal horn. In ongoing experiments, we are testing the hypothesis that activation of phrenic afferent neurons modulates contralateral phrenic motor output and arterial blood pressure in the adult rat. In anesthetized and ventilated adult Sprague‐Dawley rats, one phrenic nerve was electrically stimulated using a bipolar electrode, while respiratory bursting in the contralateral phrenic nerve and arterial blood pressure were recorded. Inspiratory triggered phrenic nerve stimulation was delivered for 20 seconds (approximately 18 breaths) at 40pps using a narrow (0.1 ms) pulse width to target activation of large diameter myelinated axons, or a wide (1.0 ms) pulse width to recruit small diameter myelinated and unmyelinated afferents. The experimental protocol consisted of eight currents (10, 25, 50, 70, 90, 120, 160, 220μA) delivered in a random order, each separated by a 5 minute recovery period (i.e. no stimulation). Each stimulus current caused a progressive increase in contralateral phrenic amplitude during the stimulation period. Phrenic amplitude remained above baseline for at least 1 minute after the cessation of stimulation. At lower currents (<50μA), the wide pulse stimulation was more effective at increasing contralateral phrenic output compared to the narrow pulse stimulation, while higher currents (>50μA) elicited a similar increase in contralateral amplitude regardless of pulse width. In addition, phrenic nerve stimulation was associated with a brief decrease, followed by an increase in mean arterial blood pressure during stimulation. In separate rats, a unilateral dorsal root rhizotomy (C3, C4, C5) was performed prior to phrenic nerve stimulation to eliminate afferent input to the spinal cord. This treatment prevented both the increase in contralateral phrenic amplitude and blood pressure at all currents and both pulse widths, indicating that the observed responses are due to activation of phrenic afferents. These preliminary results confirm that activation of phrenic afferents can modulate the activity of the contralateral phrenic motor pool, and suggest that phrenic afferents are capable of initiating phrenic motor plasticity.Support or Funding Information1F32NS095620‐01 (KS), T32‐ND043730 (MS), SPARC OT2 OD023854 (DDF), 1 R01 NS080180‐01A1 (DDF)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Long-term outcomes of intradural cervical dorsal root rhizotomy for refractory occipital neuralgia.

OBJECT Occipital neuralgia (ON) causes chronic pain in the cutaneous distribution of the greater and lesser occipital nerves. The long-term efficacy of cervical dorsal root rhizotomy (CDR) in the management of ON has not been well described. The authors reviewed their 14-year experience with CDR to assess pain relief and functional outcomes in patients with medically refractory ON. METHODS A retrospective chart review of 75 ON patients who underwent cervical dorsal root rhizotomy, from 1998 to 2012, was performed. Fifty-five patients were included because they met the International Headache Society's (IHS) diagnostic criteria for ON, responded to CT-guided nerve blocks at the C-2 dorsal nerve root, and had at least one follow-up visit. Telephone interviews were additionally used to obtain data on patient satisfaction. RESULTS Forty-two patients (76%) were female, and the average age at surgery was 46 years (range 16-80). Average follow up was 67 months (range 5-150). Etiologies of ON included the following: idiopathic (44%), posttraumatic (27%), postsurgical (22%), post-cerebrovascular accident (4%), postherpetic (2%), and postviral (2%). At last follow-up, 35 patients (64%) reported full pain relief, 11 (20%) partial relief, and 7 (16%) no pain relief. The extent of pain relief after CDR was not significantly associated with ON etiology (p = 0.43). Of 37 patients whose satisfaction-related data were obtained, 25 (68%) reported willingness to undergo repeat surgery for similar pain relief, while 11 (30%) reported no such willingness; a single patient (2%) did not answer this question. Twenty-one individuals (57%) reported that their activity level/functional state improved after surgery, 5 (13%) reported a decline, and 11 (30%) reported no difference. The most common acute postoperative complications were infections in 9% (n = 5) and CSF leaks in 5% (n = 3); chronic complications included neck pain/stiffness in 16% (n = 9) and upper-extremity symptoms in 5% (n = 3) such as trapezius weakness, shoulder pain, and arm paresthesias. CONCLUSIONS Cervical dorsal root rhizotomy provides an efficacious means for pain relief in patients with medically refractory ON. In the appropriately selected patient, it may lead to optimal outcomes with a relatively low risk of complications.

Neurogenic bladder: Highly selective rhizotomy of specific dorsal rootlets maybe a better choice

Spinal cord injury results not only in motor and sensory dysfunctions, but also in loss of normal urinary bladder functions. A number of clinical studies were focused on the strategies for improvement of functions of the bladder. Completely dorsal root rhizotomy or selective specific S2-4 dorsal root rhizotomy suppress autonomic hyper-reflexia but have the same defects: it could cause detrusor and sphincter over-relaxation and loss of reflexive erection in males. So precise operation needs to be considered. We designed an experimental trail to test the possibility on the basis of previous study. We found that different dorsal rootlets which conduct impulses from the detrusor or sphincter can be distinguished by electro-stimulation in SD rats. Highly selective rhizotomy of specific dorsal rootlets could change the intravesical pressure and urethral perfusion pressure respectively. We hypothese that for neurogenic bladder following spinal cord injury, highly selective rhizotomy of specific dorsal rootlets maybe improve the bladder capacity and the detrusor sphincter dyssynergia, and at the same time, the function of other pelvic organ could be maximize retainment.

Infrared neural stimulation of human spinal nerve roots in vivo.

Infrared neural stimulation (INS) is a neurostimulation modality that uses pulsed infrared light to evoke artifact-free, spatially precise neural activity with a noncontact interface; however, the technique has not been demonstrated in humans. The objective of this study is to demonstrate the safety and efficacy of INS in humans in vivo. The feasibility of INS in humans was assessed in patients ([Formula: see text]) undergoing selective dorsal root rhizotomy, where hyperactive dorsal roots, identified for transection, were stimulated in vivo with INS on two to three sites per nerve with electromyogram recordings acquired throughout the stimulation. The stimulated dorsal root was removed and histology was performed to determine thermal damage thresholds of INS. Threshold activation of human dorsal rootlets occurred in 63% of nerves for radiant exposures between 0.53 and [Formula: see text]. In all cases, only one or two monitored muscle groups were activated from INS stimulation of a hyperactive spinal root identified by electrical stimulation. Thermal damage was first noted at [Formula: see text] and a [Formula: see text] safety ratio was identified. These findings demonstrate the success of INS as a fresh approach for activating human nerves in vivo and providing the necessary safety data needed to pursue clinically driven therapeutic and diagnostic applications of INS in humans.

Sensory regeneration in dorsal root avulsion.

Brachial as well as lumbosacral plexus avulsion injuries are usually caused by high kinetic traumas, such as car-pedestrian, car and motorcycle accidents or falls from great heights. Traction forces affecting the head and shoulders or extremities pull the spinal nerve sleeves away from the spinal cord and rupture the postganglionic spinal root from the cord. In so called central avulsion injuries, the spinal root is avulsed at the interface between the central and peripheral nervous system (CNS and PNS). This results not only in the disconnection of the root from the cord but also in a longitudinal spinal cord injury. The complexity of the injury leads to degeneration of the spinal root and a marked inflammatory response of the spinal cord followed by the formation of a glial scar (Kachramanoglou et al., 2011).

Endogenous neurotrophin-3 promotes neuronal sprouting from dorsal root ganglia.

In the present study, we investigated the role of endogenous neurotrophin-3 in nerve terminal sprouting 2 months after spinal cord dorsal root rhizotomy. The left L1–5 and L7–S2 dorsal root ganglia in adult cats were exposed and removed, preserving the L6 dorsal root ganglia. Neurotrophin-3 was mainly expressed in large neurons in the dorsal root ganglia and in some neurons in spinal lamina II. Two months after rhizotomy, the number of neurotrophin-3-positive neurons in the spared dorsal root ganglia and the density of neurite sprouts emerging from these ganglia were increased. Intraperitoneal injection of an antibody against neurotrophin-3 decreased the density of neurite sprouts. These findings suggest that endogenous neurotrophin-3 is involved in spinal cord plasticity and regeneration, and that it promotes axonal sprouting from the dorsal root ganglia after spinal cord dorsal root rhizotomy.

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.

Neuroprosthetics for SCI Bladder Management: The Argument for Direct Bladder Stimulation

Implantable neuroprosthetic systems are an important area of practice and research in urinary care for individuals with spinal cord injury (SCI). These devices need to manage three lower urinary tract conditions: urethral sphincter contractions during bladder contractions, an underactive bladder producing poor voiding responses, and neurogenic detrusor overactivity causing urinary incontinence. Two neuroprosthetic approaches have addressed these conditions: sacral anterior root stimulation (SARS) and direct bladder wall stimulation (DBWS). The SARS approach is commercialized for SCI bladder management as the Brindley-Finetech Bladder Control System and is available in Europe. Limitations of this device include invasive surgery and the need for rhizotomy of sacral dorsal (sensory) nerve roots. The DBWS implants produced daily voiding in many SCI individuals, however, clinical use was discontinued primarily because of technical concerns with stimulators and electrodes as well as some cases of poor voiding responses and side effects. These limitations are reviewed as well as efforts to return DBWS to clinical investigations using Permaloc® Systems (Synapse Biomedical Inc., Oberlin OH). This new neuroprosthetic platform includes mapping and intramuscular electrodes as well as multilead cables and new stimulator devices.

The Majority of Dorsal Spinal Cord Gastrin Releasing Peptide is Synthesized Locally Whereas Neuromedin B is Highly Expressed in Pain- and Itch-Sensing Somatosensory Neurons

BackgroundItch is one of the major somatosensory modalities. Some recent findings have proposed that gastrin releasing peptide (Grp) is expressed in a subset of dorsal root ganglion (DRG) neurons and functions as a selective neurotransmitter for transferring itch information to spinal cord interneurons. However, expression data from public databases and earlier literatures indicate that Grp mRNA is only detected in dorsal spinal cord (dSC) whereas its family member neuromedin B (Nmb) is highly expressed in DRG neurons. These contradictory results argue that a thorough characterization of the expression of Grp and Nmb is warranted.FindingsGrp mRNA is highly expressed in dSC but is barely detectable in DRGs of juvenile and adult mice. Anti-bombesin serum specifically recognizes Grp but not Nmb. Grp is present in a small number of small-diameter DRG neurons and in abundance in layers I and II of the spinal cord. The reduction of dSC Grp after dorsal root rhizotomy is significantly different from those of DRG derived markers but similar to that of a spinal cord neuronal marker. Double fluorescent in situ of Nmb and other molecular markers indicate that Nmb is highly and selectively expressed in nociceptive and itch-sensitive DRG neurons.ConclusionThe majority of dSC Grp is synthesized locally in dorsal spinal cord neurons. On the other hand, Nmb is highly expressed in pain- and itch-sensing DRG neurons. Our findings provide direct anatomic evidence that Grp could function locally in the dorsal spinal cord in addition to its roles in DRG neurons and that Nmb has potential roles in nociceptive and itch-sensitive neurons. These results will improve our understanding about roles of Grp and Nmb in mediating itch sensation.

A comparative histological analysis of two models of nerve root avulsion injury in the adult rat

This study has investigated the reliability of the artificial surgical model dorsal root rhizotomy (DRR), to the surgical tearing of the roots, avulsion, that occurs clinically. Root avulsion of the limb nerves is common in high-impact motor vehicle accidents and results in paraesthesia, paralysis and intractable pain. Limited treatment options are largely due to a lack of basic research on underlying mechanisms, and few animal models. We assess this limitation by histologically assessing the spatial and temporal injury profile of dorsal root avulsion (DRA) and DRR within the spinal cord. Rats underwent DRR, DRA or sham surgery to the L3-L6 dorsal roots unilaterally. At 1, 2, 14, and 28 days post injury, immunohistochemical density staining was used to characterize the progression of spinal cord trauma. Neuronal (NeuN) and vascular degeneration (RECA-1), inflammatory infiltrate (ED1, anti-neutrophil), gliosis (Iba1, GFAP) and apoptosis (TUNEL) were assessed. Unilateral DRA produced a prolonged and bilateral glial and inflammatory response, and vascular degeneration compared to transient and unilateral effects after DRR. Transsynaptic neurodegeneration after DRA was greater than after DRR, and progressed across 28 days coinciding with gliosis and macrophage infiltration. Rhizotomy leads to a milder representation of the spinal cord trauma that occurs after 'true' avulsion injury. We recommend DRA be used in the future to more reliably model clinical avulsion injury. Avulsion is an injury with a chronic profile of degenerative and inflammatory progression, and this theoretically provides a window of clinical therapeutic opportunity in treatment of secondary trauma progression.

Genetic dissection of axon regeneration via in vivo electroporation of adult mouse sensory neurons

Manipulating gene expression in vivo specifically in neurons with precise spatiotemporal control is important to study the function of gene(s) or pathway(s) in the nervous system. Although various transgenic approaches or virus-mediated transfection methods are available, they are time consuming and/or lack precise temporal control. Here we introduce an efficient electroporation approach to transfect adult dorsal root ganglion (DRG) neurons in vivo that enables manipulation of gene expression in an acute and precise fashion. We have applied this method to manipulate gene expression in three widely used in vivo models of axon injury and regeneration, including dorsal column transection, dorsal root rhizotomy, and peripheral axotomy. By electroporating DRGs with siRNAs against c-jun to specifically deplete c-Jun in adult neurons, we provide evidence for the role of c-Jun in regulation of in vivo axon regeneration. This method will serve as a powerful tool to genetically dissect axon regeneration in vivo.

Quality of life in complete spinal cord injury patients with a Brindley bladder stimulator compared to a matched control group

To determine the effects on Quality of Life (QoL) of a Brindley procedure, which combines a sacral dorsal root rhizotomy to treat neurogenic detrusor overactivity with sacral anterior root stimulation to enable micturition, defecation, and penile erections in complete spinal cord injury (SCI) patients compared to a matched Control Group. Cross-sectional study. The Qualiveen questionnaire, SF-36 questionnaire, and multiple choice questions about urinary continence and urinary tract infections were sent to 93 patients who had a Brindley stimulator implanted in the Netherlands and a matched Control Group of 70 complete SCI patients with neurogenic detrusor overactivity. Primary study outcomes were Specific Impact of Urinary Problems score and general QoL index of the Qualiveen. Response rates were 78% and 40% for patients with a Brindley stimulator and controls, respectively. Stimulators were still used for micturition in 46 (63%). These patients had a significant better Specific Impact of Urinary Problems score, general QoL index (Qualiveen), and continence rate, and less urinary tract infections compared to the Control Group. Patients also benefited of the rhizotomy with regard to QoL and continence rate if the stimulator was not used anymore. The subscales of the SF-36 had better scores for the patients who used their stimulator as compared to those who did not use the stimulator and compared to the Control Group. The Brindley stimulator for complete spinal cord injury patients improves Quality of Life, continence, and urinary tract infection rate compared to a matched Control Group.

Neural progenitors promote axon growth in vitro and ex vivo but not following injury.

Following an injury to the dorsal roots primary sensory afferents fail to regenerate past the hostile dorsal root entry zone (DREZ), the interface between the peripheral and central nervous system. Neural progenitor cells have previously been utilised as a cellular replacement therapy in a variety of CNS injury models. Here we show for the first time that NPCs are capable of promoting neurite outgrowth from adult sensory neurons in vitro and ex vivo cryo-cultures. The effectiveness of NPCs as a potential means of promoting regeneration of primary afferents across the DREZ was assessed following rhizotomy at the cervical level in the adult rat. Adult rats were subjected to rhizotomy of the dorsal roots between C(5)-T(1) which were then reanastamosed. In conjunction with the rhizotomy NPCs were delivered at the DREZ. NPCs survived transplantation and were observed to differentiate predominantly into glia. Regeneration of the dorsal root fibers was assessed with immunhistochemical analysis of the large and small diameter peptidergic and non-peptidergic afferents. Although afferents appeared near to the DREZ there was little regeneration beyond the DREZ. Furthermore, no significant improvement was observed in behavioural tasks.

Cell death after dorsal root injury

Flow cytometry and terminal deoxynucleotidyl transferase-mediated biotinylated uridine triphosphate nick end-labelling (TUNEL) immunohistochemistry have been used to assess cell death in the dorsal root ganglia (DRG) or spinal cord 1, 2 or 14 days after multiple lumbar dorsal root rhizotomy or dorsal root avulsion injury in adult rats. Neither injury induced significant cell death in the DRG compared to sham-operated or naïve animals at any time point. In the spinal cord, a significant increase in death was seen at 1-2 days, but not 14 days, post injury by both methods. TUNEL staining revealed that more apoptotic cells were present in the dorsal columns and dorsal horn of avulsion animals compared to rhizotomised animals. This suggests that avulsion injury, which can often partially damage the spinal cord, has more severe effects on cell survival than rhizotomy, a surgical lesion which does not affect the spinal cord. The location of TUNEL positive cells suggests that both neuronal and non-neuronal cells are dying.

Effects of selective unilateral dorsal root(s) rhizotomy on micturition reflex in anesthetized rats

To clarify the contributions of sensory inputs and glutamate transmissions to the spinal micturition reflex. Cystometrogram and external urethral sphincter electromyogram activities evaluated the L6 and/or S1 levels. Changes in intravesicular pressure (IVP) in response to saline infusion (0.1 ml/min) were found after unilateral dorsal root rhizotomy at the L6 level, which showed significant increases in threshold pressure (rhizotomized vs. control: 14.25 +/- 0.82 vs. 8.40 +/- 0.69 cmH(2)O, P < 0.01, n = 28), post-voiding pressure (7.66 +/- 0.56 vs. 5.42 +/- 0.52 cmH(2)O, P < 0.01, n = 28), holding duration (135.06 +/- 23.6 vs. 77.73 +/- 13.56 sec, P < 0.05, n = 28), and inter-contraction interval (140.62 +/- 23.29 vs. 82.40 +/- 13.57 sec, P < 0.05, n = 28). Several (mean = 2.32 +/- 1.31 vs. 0.12 +/- 0.21, P < 0.01, n = 28, P < 0.01, n = 28) non-voiding contractions with gradual increase in IVP were found ahead of voiding contraction after rhizotomy. An additional dorsal root rhizotomy at the ipsilateral S1 level caused further increases in urodynamic parameters (threshold pressure, 18.18 +/- 1.67 cmH(2)O, P < 0.01; post-voiding pressure 8.07 +/- 0.96 cmH(2)O, P < 0.01; holding duration, 211.44 +/- 42.54 sec, P < 0.01; inter-contraction interval, 264.2 +/- 59.99 sec, P < 0.05; non-voiding contractions, 4.41 +/- 2.12, P < 0.01, n = 7). Intrathecal glutamate (100 microM, 10 microl) ameliorated all the pathological conditions induced by unilateral dorsal root rhizotomy at the L6 level in a dose dependent manner (ED(50) = 1.25 +/- 10(-5)). Intrathecal CNQX (6-cyano-7-nitroquinoxaline-2,3-dione; 100 microM, 10 microl) and APV (D-2-amino-5-phosphonovaleric acid; 100 microM, 10 microl) injections after rhizotomy at the L6 level induced disturbances similar to that caused by an additional rhizotomy at ipsilateral S1 level. Wherease, glutamate (100 microM, 10 microl) reversed the disturbances caused by CNQX but showed no effect on that by APV. Acute partial sensory deprivation caused acute impaired micturition reflex in rat models. In addition, glutamatergic NMDA and AMPA receptors are important for mediating these impairments in micturition reflex.

Impaired micturition reflex caused by acute selective dorsal or ventral root(s) rhizotomy in anesthetized rats

To clarify the contributions of parasympathetic inputs and outputs to the micturition reflex. Intra-vesical pressure (IVP), external urethral sphincter electromyogram (EMG), pelvic afferent nerve activities (PANA), and pelvic efferent nerve activities (PENA) as well as the time-derived IVP (dIVP, an index of bladder contractility) were evaluated in intact and acute dorsal or ventral root(s) rhizotomized (DRX and VRX, respectively) rats. In DRX rats, when compared with that in intact stage, the voiding frequency was decreased (75 +/- 15% of intact, P < 0.05, n = 8), while the threshold pressure to trigger voiding contractions was significantly increased (187 +/- 75% of intact, P < 0.05, n = 8). In addition, several insufficient contractions (5.3 +/- 3.5 contractions/voiding, P < 0.05, n = 8) occurred in ahead of each voiding contraction. On the other hand, in VRX rats, the peak and rebound IVP were significantly decreased (90 +/- 3.5% and 75 +/- 11.3% of intact, P < 0.01, n = 8), while the threshold pressure was not affected (102 +/- 11% of intact, P = NS, n = 8). The time-derived parameters were significantly decreased in VRX (peak dIVP, 78 +/- 10.2%, rebound dIVP, 75 +/- 15.6%, minimal dIVP, 68 +/- 14% of intact, P < 0.01, n = 8) but only peak dIVP was decreased (85 +/- 11% of intact, P < 0.01, n = 8) in DRX rats. Acute selective DRX and VRX rat can be an animal model to investigate peripheral neural control in micturition functions.