scholarly journals Biomehanicke karakteristike tkiva kicmene mozdine - osnov za razvoj modifikovane tehnike DREZ operacije

2004 ◽  
Vol 51 (4) ◽  
pp. 59-64
Author(s):  
M. Spaic ◽  
Dusan Mikicic ◽  
S. Ilic ◽  
I. Milosavljevic ◽  
S. Ivanovic ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Spinal Cord ◽  
Dorsal Horn ◽  
Cauda Equina ◽  
Spinal Cord Tissue ◽  
Management Problem ◽  
Tissue Elasticity ◽  
Neurogenic Pain ◽  
Size And Shape ◽  
Drez Lesion

Mechanical properties of the spinal cord tissue - biological basis for the development of the modality of the DREZ surgery lesioning technique Successful treatment of the chronic neurogenic pain of spinal cord and cauda equina injury origin remains a significant management problem. The mechanism of this pa-in phenomenon has been shown to be related to neurochemical changes that lead to the state of hypereactivity of the second order dorsal horn neurons. The DREZ surgery (Dorsal Root Entry Zone lesion), designed to destroy anatomy structures involved in pain generating thus interrupting the neurogenic pain mechanism, as a causative procedure in treating this chronic pain, has been performed by using different technical modalities: Radiofrequency (RF) coagulation technique, Laser, Ultrasound and Microsurgical DREZotomy technic. The purpose of the study was to assess the possibility for the establishment of the lesioning technique based on the natural difference in the mechanical properties between the white and gray cord substance. We experimentally determinate mechanical properties of the human cadaveric cord white versus gray tissue for the purpose of testing possibility of selective suction of the dorsal horn gray substance as a DREZ lesioning procedure. Based on the fact of the difference in tissue elasticity between white and gray cord substance we established a new and simple DREZ surgical lesioning technique that was tested on cadaver cord. For the purpose of testing and comparing the size and shape of the DREZ lesion achieved the DREZ surgery has been performed on cadaver cord by employing selective dorsal horn suction as a lesioning method. After the procedure cadaver cord underwent histological fixation and analysis of the DREZ lesions achieved. Our result revealed that the white cord substance with longitudinal fiber structure had four time higher dynamical viscosity than gray substance of local neuronal network structure (150 PaS versus 37,5 PaS) that provided possibility for the safe and selective suction of the gray substance of the dorsal horn. Technique includes incision of the dorsolateral sulcus according to Sindous Microsurgical DREZotomy technique than suction under visual control of the dorsal horn gray matter using sucker adopted from the lumbar puncture nidle. Operative experimental testing and hystological analysis confirmed expected size and shape of the DREZ lesion performed by dorsal horn suction as DREZ lesioning technique. The utility, selectivity and safety of this technique has been provided by the natural mechanical properties of the cord tissue itself. Application of the Dorsal horn suction as a DREZ lesioning in humans confirmed this technique as a safe and reliable DREZ lesioning method.

scholarly journals Pregabalin alleviates postherpetic neuralgia by downregulating spinal TRPV1 channel protein

2021 ◽  
Vol 20 (11) ◽  
pp. 2287-2292
Author(s):  
Zhenping Xiao ◽  
Mengjun Liao ◽  
Yunwu He ◽  
Yonglin Li ◽  
Wuzhou Yang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Postherpetic Neuralgia ◽  
New Drugs ◽  
Spinal Cord Tissue ◽  
Sprague Dawley ◽  
Trpv1 Channel ◽  
Channel Protein ◽  
Tnf Α ◽  
Prefrontal Lobe

Purpose: To determine the mechanism involved in pregabalin-induced alleviation of postherpetic neuralgia in a rat model.Methods: Ninety-sixty healthy Sprague-Dawley (SD) rats were assigned to sham, model andpregabalin groups (32 rats per group). A model of postherpetic neuralgia (PN) was established. The expressions of IL-1β and TNF-α in spinal cord tissue were determined 7 days after administration of treatments. The proportions of fluorescence areas in astrocytes in the dorsal horn, prefrontal lobe and hippocampus, and level of spinal cord TRPV1 channel protein in each group were evaluated.Results: Relative to model rats, IL-1β and TNF-α in spinal cord of pregabalin rats were significantly reduced (p < 0.05). The areas of fluorescence in astrocytes in dorsal horn of spinal cord, prefrontal lobe and hippocampus of model group were significantly increased, relative to sham, but were decreased in rats in pregabalin group (p < 0.05).Conclusion: Pregabalin significantly alleviates postherpetic neuralgia via mechanisms which may be related to the inflammatory response of spinal dorsal horn and downregulation of TRPV1 channel protein expression. This finding may be useful in developing new drugs for alleviating postherpetic neuralgia.

Intravenous Morphine Increases Release of Nitric Oxide From Spinal Cord by an α-Adrenergic and Cholinergic Mechanism

1997 ◽  
Vol 78 (4) ◽  
pp. 2072-2078 ◽  
Author(s):  
Zemin Xu ◽  
Chuanyao Tong ◽  
Hui-Lin Pan ◽  
Sergio E. Cerda ◽  
James C. Eisenach
Keyword(s):  
Nitric Oxide ◽  
Spinal Cord ◽  
Dorsal Horn ◽  
Cervical Spinal Cord ◽  
Intrathecal Injection ◽  
Spinal Cord Tissue ◽  
Cholinergic Mechanism ◽  
Adrenergic Antagonist ◽  
Opioid Administration ◽  
Intravenous Morphine

Xu, Zemin, Chuanyao Tong, Hui-Lin Pan, Sergio E. Cerda, and James C. Eisenach. Intravenous morphine increases release of nitric oxide from spinal cord by an α-adrenergic and cholinergic mechanism. J. Neurophysiol. 78: 2072–2078, 1997. Systemic opioids produce analgesia in part by activating bulbospinal noradrenergic pathways. Spinally released norepinephrine (NE) has been suggested to produce analgesia in part by stimulating α2-adrenoceptors on cholinergic spinal interneurons to release acetylcholine (ACh). We hypothesized that this spinally released ACh would stimulate synthesis of nitric oxide (NO), and that spinally released NO after intravenous (IV) opioid injection thus would depend on a cascade of noradrenergic and cholinergic receptor stimulation. To test these hypotheses, IV morphine was administered to anesthetized sheep, and neurotransmitters in dorsal horn interstitial fluid were measured by microdialysis. IV morphine increased NE and ACh in dorsal horn microdialysates, and these increases were inhibited by IV naloxone or cervical spinal cord transection. IV morphine also increased dorsal horn microdialysate concentrations of nitrite, a stable metabolite of NO. Increases in NE, ACh, and nitrite were antagonized by prior intrathecal injection of the α2-adrenergic antagonist idazoxan, the muscarinic antagonist atropine, or the NO synthase inhibitor N-methyl-l-arginine (NMLA). To examine the concentration-dependent effects of spinal adrenergic stimulation, isolated rat spinal cord tissue was perfused with the α2-adrenergic agonist clonidine. Clonidine increased nitrite in the spinal cord tissue perfusate, an effect blocked by coadministration of idazoxan, atropine, and NMLA. These data support a previously hypothesized cascade of spinally released NE and ACh after systemic opioid administration. These data also suggest that spinally released NO plays a role in the analgesic effects of systemic opioids. In addition, these data imply a positive feedback whereby spinally released nitric oxide increases NE release and that has not previously been described.

scholarly journals Evaluation of Spinal Toxicity and Long-term Spinal Reflex Function after Intrathecal Levobupivaciane in the Neonatal Rat

2013 ◽  
Vol 119 (1) ◽  
pp. 142-155 ◽  
Author(s):  
Emre Hamurtekin ◽  
Bethany L. Fitzsimmons ◽  
Veronica I. Shubayev ◽  
Marjorie R. Grafe ◽  
Ronald Deumens ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Caspase 3 ◽  
Cauda Equina ◽  
Safety Data ◽  
Spinal Reflex ◽  
Neonatal Rat ◽  
Spinal Cord Tissue ◽  
Drug Induced ◽  
Rat Pups

Abstract Background: Neuraxial anesthesia is utilized in children of all ages. Local anesthetics produce dose-dependent toxicity in certain adult models, but the developing spinal cord may also be susceptible to drug-induced apoptosis. In postnatal rodents, we examined the effects of intrathecal levobupivacaine on neuropathology and long-term sensorimotor outcomes. Methods: Postnatal day 3 (P3) or P7 rat pups received intrathecal levobupivacaine 2.5 mg/kg (0.5%) or saline. Mechanical withdrawal thresholds and motor block were assessed. Spinal cord tissue analysis included apoptosis counts (activated caspase-3, Fluoro-Jade C) at 24 h, glial reactivity at 7 days, and histopathology in cord and cauda equina at 24 h and 7 days. Long-term spinal function in young adults (P35) was assessed by hind limb withdrawal thresholds, electromyography responses to suprathreshold stimuli, and gait analysis. Results: Intrathecal levobupivacaine produced spinal anesthesia at P3 and P7. No increase in apoptosis or histopathological change was seen in the cord or cauda equina. In the P3 saline group, activated caspase-3 (mean ± SEM per lumbar cord section 6.1 ± 0.3) and Fluoro-Jade C (12.1 ± 1.2) counts were higher than at P7, but were not altered by levobupivacaine (P = 0.62 and P = 0.11, two-tailed Mann–Whitney test). At P35, mechanical withdrawal thresholds, thermal withdrawal latency, and electromyographic reflex responses did not differ across P3 or P7 levobupivacaine or saline groups (one way ANOVA with Bonferroni comparisons). Intrathecal bupivacaine at P3 did not alter gait. Conclusion: Single dose intrathecal levobupivacaine 0.5% did not increase apoptosis or produce spinal toxicity in neonatal rat pups. This study provides preclinical safety data relevant to neonatal use of neuraxial local anesthesia.

Somatosensory function following dorsal root entry zone lesions in patients with neurogenic pain or spasticity

1991 ◽  
Vol 74 (6) ◽  
pp. 916-932 ◽  
Author(s):  
Daniel Jeanmonod ◽  
Marc Sindou
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Dorsal Root ◽  
Neurogenic Pain ◽  
Entry Zone ◽  
Dorsal Root Entry Zone ◽  
Content Type ◽  
Root Entry Zone ◽  
Somatosensory Function ◽  
Fine Print

✓ The goal of this study was to assess the effects of the dorsal root entry zone (DREZ) lesioning procedure, microsurgical DREZ-otomy (MDT), on spinal cord somatosensory function based on peri- and intraoperative clinical and electrophysiological data. The study was performed prospectively on a series of 20 patients suffering from either chronic neurogenic pain or spasticity. Physiological observations were made of the intraoperative evoked electrospinographic recordings as collected from the surface of the spinal cord. The MDT procedure produced analgesia or severe hypalgesia, moderate hypesthesia, and only slight deficits in proprioception and cutaneous spatial discrimination on the body segments operated on. These clinical data correlated well with evoked electrospinographic recordings, which showed a moderate effect of MDT on presynaptic compound action potentials recorded from the spinal cord (N11 and N21), a partial or even reversible effect on the cortical postcentral N20 wave, a more marked effect on the postsynaptic dorsal horn waves N13 and N24 related to large primary afferent fibers, and a disappearance of dorsal horn waves related to finer afferents (N2 and possibly N3). These data provide evidence for an acceptably selective action of MDT on spinal cord nociceptive mechanisms, and for a partial, often slight, involvement of the other somatosensory domains. The presence of abnormal evoked electrospinographic waves is discussed in relation to the mechanisms of neurogenic pain and spasticity. The hypothesis of a “retuning” of the dorsal horn as the mode of action of MDT is presented.

scholarly journals Dorsal Horn of Mouse Lumbar Spinal Cord Imaged with CLARITY

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Gulgun Sengul ◽  
Huazheng Liang ◽  
Teri M. Furlong ◽  
George Paxinos
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Aminobutyric Acid ◽  
Lumbar Spinal Cord ◽  
Spinal Cord Tissue ◽  
Gamma Aminobutyric Acid ◽  
Immunohistochemical Markers ◽  
Calcitonin Gene ◽  
Clearing Technique ◽  
Lumbar Spinal

The organization of the mouse spinal dorsal horn has been delineated in 2D for the six Rexed laminae in our publication Atlas of the Spinal Cord: Mouse, Rat, Rhesus, Marmoset, and Human. In the present study, the tissue clearing technique CLARITY was used to observe the cyto- and chemoarchitecture of the mouse spinal cord in 3D, using a variety of immunohistochemical markers. We confirm prior observations regarding the location of glycine and serotonin immunoreactivities. Novel observations include the demonstration of numerous calcitonin gene-related peptide (CGRP) perikarya, as well as CGRP fibers and terminals in all laminae of the dorsal horn. We also observed sparse choline acetyltransferase (ChAT) immunoreactivity in small perikarya and fibers and terminals in all dorsal horn laminae, while gamma aminobutyric acid (GABA) and glutamate decarboxylase-67 (GAD67) immunoreactivities were found only in small perikarya and fibers. Finally, numerous serotonergic fibers were observed in all laminae of the dorsal horn. In conclusion, CLARITY confirmed the 2D immunohistochemical properties of the spinal cord. Furthermore, we observed novel anatomical characteristics of the spinal cord and demonstrated that CLARITY can be used on spinal cord tissue to examine many proteins of interest.

scholarly journals Mechanical mapping of spinal cord development and repair in living zebrafish larvae using Brillouin microscopy

2017 ◽  
Author(s):  
Raimund Schlüßler ◽  
Stephanie Möllmert ◽  
Shada Abuhattum ◽  
Gheorghe Cojoc ◽  
Paul Müller ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Spinal Cord ◽  
Measurement Techniques ◽  
Biological Tissues ◽  
Tissue Mechanics ◽  
Spinal Cord Tissue ◽  
Tissue Properties ◽  
Zebrafish Larvae ◽  
Cord Injury

AbstractThe mechanical properties of biological tissues are increasingly recognized as important factors in developmental and pathological processes. Most existing mechanical measurement techniques either necessitate destruction of the tissue for access or provide insufficient spatial resolution. Here, we show for the first time a systematic application of confocal Brillouin microscopy to quantitatively map the mechanical properties of spinal cord tissues during biologically relevant processes in a contact-free and non-destructive manner. Living zebrafish larvae were mechanically imaged in all anatomical planes, during development and after spinal cord injury. These experiments revealed that Brillouin microscopy is capable of detecting the mechanical properties of distinct anatomical structures without interfering with the animal’s natural development. The Brillouin shift within the spinal cord increased during development and transiently decreased during the repair processes following spinal cord transection. By taking into account the refractive index distribution, we explicitly determined the apparent longitudinal modulus and viscosity of different larval zebrafish tissues. Importantly, mechanical properties differed between tissues in situ and in excised slices. The presented work constitutes the first step towards an in vivo assessment of spinal cord tissue mechanics during regeneration, provides a methodical basis to identify key determinants of mechanical tissue properties and allows to test their relative importance in combination with biochemical and genetic factors during developmental and regenerative processes.

scholarly journals Inhibition of Glycine Re-Uptake: A Potential Approach for Treating Pain by Augmenting Glycine-Mediated Spinal Neurotransmission and Blunting Central Nociceptive Signaling

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 864
Author(s):  
Christopher L. Cioffi
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Therapeutic Potential ◽  
Opioid Analgesic ◽  
Critical Role ◽  
Analgesic Efficacy ◽  
Standard Of Care ◽  
Current Standard ◽  
Glycine Transporters ◽  
Pathological Pain

Among the myriad of cellular and molecular processes identified as contributing to pathological pain, disinhibition of spinal cord nociceptive signaling to higher cortical centers plays a critical role. Importantly, evidence suggests that impaired glycinergic neurotransmission develops in the dorsal horn of the spinal cord in inflammatory and neuropathic pain models and is a key maladaptive mechanism causing mechanical hyperalgesia and allodynia. Thus, it has been hypothesized that pharmacological agents capable of augmenting glycinergic tone within the dorsal horn may be able to blunt or block aberrant nociceptor signaling to the brain and serve as a novel class of analgesics for various pathological pain states. Indeed, drugs that enhance dysfunctional glycinergic transmission, and in particular inhibitors of the glycine transporters (GlyT1 and GlyT2), are generating widespread interest as a potential class of novel analgesics. The GlyTs are Na+/Cl−-dependent transporters of the solute carrier 6 (SLC6) family and it has been proposed that the inhibition of them presents a possible mechanism by which to increase spinal extracellular glycine concentrations and enhance GlyR-mediated inhibitory neurotransmission in the dorsal horn. Various inhibitors of both GlyT1 and GlyT2 have demonstrated broad analgesic efficacy in several preclinical models of acute and chronic pain, providing promise for the approach to deliver a first-in-class non-opioid analgesic with a mechanism of action differentiated from current standard of care. This review will highlight the therapeutic potential of GlyT inhibitors as a novel class of analgesics, present recent advances reported for the field, and discuss the key challenges associated with the development of a GlyT inhibitor into a safe and effective agent to treat pain.

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