scholarly journals Radiosurgery to the Spinal Dorsal Root Ganglion Induces Fibrosis and Inhibits Peripheral Glial Cell Activation While Preserving Axonal Neurotransmission

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Ezequiel Goldschmidt ◽  
Wendy Fellows-Mayle ◽  
Ajay Niranjan ◽  
John Flickinger ◽  
L Dade Lunsford ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Cell Activation ◽  
The Body ◽  
Male Rats ◽  
Gasserian Ganglion ◽  
Sprague Dawley ◽  
Spinothalamic Tract ◽  
Satellite Glial Cells ◽  
Sensory Deficits

Abstract INTRODUCTION Stereotactic radiosurgery (SRS) is an effective technique to create lesions in the trigeminal nerve to treat trigeminal neuralgia. The lumbar dorsal root ganglion (DRG) contains the body of the sensory neurons responsible for pain. Therefore, SRS to the DRG might improve radiculopathic pain. This study was performed to examine the functional and structural effects of 40 or 80 Gy to the DRG in a rat model. METHODS A total of 8 Sprague Dawley male rats underwent 40 or 80 Gy single fraction SRS to the left L5 and L6 DRGs using the Leksell Gamma Knife Icon. The contralateral DRG served as controls. Animals were sacrificed after 3 mo, and the spines were harvested. Common histology was used to assess fibrosis and inflammation. DRGs were stained for Glial Fibrillar Acidic Protein (GFAP) and Neu-N as a measure of peripheral glial activation and neurogenesis respectively. The Von Frey Test was used to assess the integrity of the spinothalamic tract. Animals were evaluated for motor and sensory deficits bi-weekly. RESULTS No motor or sensory deficits resulted from SRS in any animal. Histological changes including fibrosis, edema, and vascular sclerosis were present on the treated, but not the control side and were more pronounced at the higher dose. SRS reduced the expression of GFAP without affecting the expression of Neu-N or internexin. The Von Frey Test did not show any differences between the two sides at either dose. CONCLUSION Both doses were well tolerated and provoked no deficits, neuronal lysis, or altered the function of spinothalamic axons. SRS reduced the activation of satellite glial cells, a primary mechanism for DRG mediated pain, and elicited similar changes as the ones described to the Gasserian ganglion after SRS signaling that SRS might be effective for the treatment of refractory radiculopathic pain.

312 An Evaluation of the Clinical and Histological Effects of High Dose Radiosurgery on the Rat Dorsal Root Ganglion

Neurosurgery ◽  
2017 ◽  
Vol 64 (CN_suppl_1) ◽  
pp. 266-267
Author(s):  
Ezequiel Goldschmidt ◽  
Wendy Fellows-Mayle ◽  
Erin Paschel ◽  
Ajay Niranjan ◽  
John Flickinger ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
The Body ◽  
Male Rats ◽  
High Dose ◽  
Sprague Dawley ◽  
Histopathological Response ◽  
Histological Techniques ◽  
Sensory Deficits ◽  
The Right

Abstract INTRODUCTION Stereotactic radiosurgery (SRS) is a safe and effective technique to create lesions of the brain and trigeminal nerve (TGN) in order to achieve neuromodulation. The lumbar dorsal root ganglion (DRG) contains the body of the sensory neurons responsible for pain sensitivity and can be targeted to treat chronic and debilitating pain in the extremities. Neuromodulation of the DRG might therefore improve chronic peripheral pain. This study was performed to determine the feasibility as well as clinical and histological effects of delivering high dose SRS targeted to the lumbar DRG in a rat model. METHODS Four Sprague Dawley male rats underwent 80 Gy maximum dose single-fraction SRS to the left L5 and L6 DRG using the Leksell Gamma Knife Icon (Elekta, Atlanta, GA) with onboard cone-beam CT imaging using 4 mm diameter collimators. The right L5 and L6 DRGs served as the controls. The animals were evaluated for motor and sensory deficits every two weeks. Two animals were sacrificed at 3 and two at 6 months after SRS. The lumbar spines were harvested and decalcified. Common histological techniques (Masson trichrome, Prussian blue) were used to assess for fibrosis and demyelination. RESULTS >No detectable motor or sensory deficits were seen in any animal. Histological changes including fibrosis and loss of myelin were noted to the left L5 and L6 DRGs, but not the right side control DRGs. Fibrotic changes within the vertebral body were also evident on the treated sides of the vertebral bodies. CONCLUSION We were able to detect a demyelinating histopathological response from SRS delivered to the DRG in rats. Since such changes mimic those seen after trigeminal SRS in experimental animals, we hypothesize that radiosurgery may be a potential option in chronic spinal radicular pain amenable to neuromodulation.

scholarly journals Radiosurgery to the spinal dorsal root ganglion induces fibrosis and inhibits satellite glial cell activation while preserving axonal neurotransmission

2020 ◽  
Vol 32 (6) ◽  
pp. 790-798 ◽  
Author(s):  
Ezequiel Goldschmidt ◽  
Wendy Fellows-Mayle ◽  
Rachel Wolfe ◽  
Ajay Niranjan ◽  
John C. Flickinger ◽  
...  
Keyword(s):  
Lumbar Spine ◽  
Substance P ◽  
Dorsal Root Ganglion ◽  
Trigeminal Neuralgia ◽  
Dorsal Root ◽  
High Dose ◽  
Gasserian Ganglion ◽  
Spinothalamic Tract ◽  
Satellite Glial Cells ◽  
Control Side

OBJECTIVEStereotactic radiosurgery (SRS) has been used to treat trigeminal neuralgia by targeting the cisternal segment of the trigeminal nerve, which in turn triggers changes in the gasserian ganglion. In the lumbar spine, the dorsal root ganglion (DRG) is responsible for transmitting pain sensitivity and is involved in the pathogenesis of peripheral neuropathic pain. Therefore, radiosurgery to the DRG might improve chronic peripheral pain. This study evaluated the clinical and histological effects of high-dose radiosurgery to the DRG in a rodent model.METHODSEight Sprague-Dawley rats received either 40- or 80-Gy SRS to the fifth and sixth lumbar DRGs using the Leksell Gamma Knife Icon. Animals were euthanized 3 months after treatment, and the lumbar spine was dissected and taken for analysis. Simple histology was used to assess collagen deposition and inflammatory response. GFAP, Neu-N, substance P, and internexin were used as a measure of peripheral glial activation, neurogenesis, pain-specific neurotransmission, and neurotransmission in general, respectively. The integrity of the spinothalamic tract was assessed by means of the von Frey test.RESULTSThe animals did not exhibit any signs of motor or sensory deficits during the experimentation period. Edema, fibrosis, and vascular sclerotic changes were present on the treated, but not the control, side. SRS reduced the expression of GFAP without affecting the expression of Neu-N, substance P, or internexin. The von Frey sensory perception elicited equivalent results for the control side and both radiosurgical doses.CONCLUSIONSSRS did not alter sensory or motor function but reduced the activation of satellite glial cells, a pathway for DRG-mediated pain perpetuation. Radiosurgery provoked changes equivalent to the effects of focal radiation on the trigeminal ganglion after SRS for trigeminal neuralgia, suggesting that radiosurgery could be successful in relieving radiculopathic pain.

Histopathological Changes of Organs (Lungs, Liver, Kidney, and Brain) After Using Two Types of AgiCoat and Acticoat Nanosilver Dressings on Deep Second-Degree Burn in Rat

2019 ◽  
Vol 41 (1) ◽  
pp. 141-150 ◽  
Author(s):  
Hamid Karimi ◽  
Noor-Ahmad Latifi ◽  
Ali Zare Mehrjerdi ◽  
Babak Jafarnejad ◽  
Ali-Mohammad Karimi
Keyword(s):  
Wound Healing ◽  
Silver Ions ◽  
The Body ◽  
Male Rats ◽  
Histopathological Changes ◽  
Sprague Dawley ◽  
Tissue Samples ◽  
Degree Burn ◽  
Significant Difference ◽  
Second Degree

Abstract Prevention of infections is a very important issue in treating the burn wounds. The nanosilver dressings have many promising advantages, but absorption of silver ions and its adverse effects to the body were always a question. The aim of this study was to compare Silver serum levels and acute toxic effects of nanosilver on histopathology of organs (lungs, liver, kidney, spleen, and brain) in two types of AgiCoat and Acticoat (nanosilver) dressings on second-degree deep burn in rat. This is an experimental study conducted in our animal laboratory. We divided 24 Sprague–Dawley male rats weighing 300 to 350 randomly into two groups. After anesthesia, a second deep-degree burn was made over dorsal skins of rats by standard method. For group A, Agicoat and, for group B, Acticoat dressings were used. The dressings were changed every 3 days with AgiCoat and Acticoat, respectively. After 14 days, we got blood samples and tissue samples taken from heart, liver, kidneys, spleen, lungs, and brain and a sample from dorsal skin of the rat for histopathological examinations. The results showed that the levels of serum silver in both groups were significantly higher than the standard level (1.22 part per million (PM); AgiCoat, P = .017; Acticoat, P = .000), but there was no significant difference between the groups (P = .551). Examination of the relationship between the level of serum silver and histopathological changes in liver showed that hepatotoxicity of AgiCoat was higher compared with Acticoat and the difference was significant (P = .002). There were no pathological changes in brain, kidneys, spleen, heart, and lungs. Wound healing was faster in Acticoat group. The nanosilver dressings can cause toxicity in liver but not in kidney, brain, spleen, heart, and lungs. Liver pathology and hepatotoxicity were more prominent in AgiCoat group. Wound healing was faster in Acticoat group.

Perspectives in Pain Research 2014: Neuroinflammation and glial cell activation: The cause of transition from acute to chronic pain?

2015 ◽  
Vol 6 (1) ◽  
pp. 3-6 ◽  
Author(s):  
Brian E. Cairns ◽  
Lars Arendt-Nielsen ◽  
Paola Sacerdote
Keyword(s):  
Spinal Cord ◽  
Chronic Pain ◽  
Dorsal Root Ganglion ◽  
Glial Cell ◽  
Schwann Cells ◽  
Glial Cells ◽  
Proinflammatory Cytokines ◽  
Immune Cells ◽  
Dorsal Root ◽  
Satellite Glial Cells

AbstractBackgroundIt is unknown why an acute pain condition under various circumstances can transition into a chronic pain condition.There has been a shift towards neuroinflammation and hence glial cell activations specifically in the dorsal root ganglion and spinal cord as a mechanism possibly driving the transition to chronic pain. This has led to a focus on non-neuronal cells in the peripheral and central nervous system. Besides infiltrating macrophages, Schwann cells and satellite glial cells release cytokines and therefore important mechanisms in the maintenance of pain. Activated Schwann cells, satellite glial cells, microglia, and astrocytes may contribute to pain sensitivity by releasing cytokines leading to altered neuronal function in the direction of sensitisation.Aims of this perspective paper1) Highlight the complex but important recent achievement in the area of neuroinflammation and pain at spinal cord level and in the dorsal root ganglion.2) Encourage further research which hopefully may provide better understanding of new key elements driving the transition from acute to chronic pain.Recent results in the area of neuroinflammation and painFollowing a sciatic nerve injury, local macrophages, and Schwann cells trigger an immune response immediately followed by recruitment of blood-derived immune cells. Schwann cells, active resident, and infiltrating macrophages release proinflammatory cytokines. Proinflammatory cytokines contribute to axonal damage and also stimulate spontaneous nociceptor activity. This results in activation of satellite glial cells leading to an immune response in the dorsal root ganglia driven by macrophages, lymphocytes and satellite cells. The anterograde signalling progresses centrally to activate spinal microglia with possible up regulation of glial-derived proinflammatory/pronociceptive mediators.An important aspect is extrasegmental spreading sensitisation where bilateral elevations in TNF-α, IL-6, and IL-10 are found in dorsal root ganglion in neuropathic models. Similarly in inflammatory pain models, bilateral up regulation occurs for TNF-α, IL-1 β, and p38 MAPK. Bilateral alterations in cytokine levels in the DRG and spinal cord may underlie the spread of pain to the uninjured side.An important aspect is how the opioids may interact with immune cells as opioid receptors are expressed by peripheral immune cells and thus can induce immune signaling changes. Furthermore, opioids may stimulate microglia cells to produce proinflammatory cytokines such as IL-1.ConclusionsThe present perspective paper indicates that neuroinflammation and the associated release of pro-inflammatory cytokines in dorsal root ganglion and at the spinal cord contribute to the transition from acute to chronic pain. Neuroinflammatory changes have not only been identified in the spinal cord and brainstem, but more recently, in the sensory ganglia and in the nerves as well. The glial cell activation may be responsible for contralateral spreading and possible widespread sensitisation.ImplicationsCommunication between glia and neurons is proposed to be a critical component of neuroinflammatory changes that may lead to chronic pain. Sensory ganglia neurons are surrounded by satellite glial cells but how communication between the cells contributes to altered pain sensitivity is still unknown. Better understanding may lead to new possibilities for (1) preventing development of chronic pain and (2) better pain management.

Exposure of the Dorsal Root Ganglion in Rats to Pulsed Radiofrequency Currents Activates Dorsal Horn Lamina I and II Neurons

Neurosurgery ◽  
2002 ◽  
Vol 50 (4) ◽  
pp. 850-856 ◽  
Author(s):  
Yoshinori Higuchi ◽  
Blaine S. Nashold ◽  
Menno Sluijter ◽  
Eric Cosman ◽  
Robert D. Pearlstein
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Horn ◽  
Dorsal Root ◽  
Spinal Pain ◽  
Pulsed Radiofrequency ◽  
Sprague Dawley ◽  
Current Electrode ◽  
Spinal Cord Neurons ◽  
Dorsal Ganglion ◽  
Pulsed Rf

Abstract OBJECTIVE: Application of pulsed radiofrequency (RF) currents to the dorsal ganglion has been reported to produce long-term relief of spinal pain without causing thermal ablation. The present study was undertaken to identify spinal cord neurons activated by exposure of the dorsal ganglion to pulsed RF currents in rats. METHODS: Left-sided hemilaminectomy was performed in adult Sprague-Dawley rats to expose the C6 dorsal root ganglion. An RF electrode (0.5 mm diameter) with a thermocouple for temperature monitoring was positioned on the exposed ganglion, and rats were assigned to one of three treatment groups: pulsed RF treatment (20 ms of 500-kHz RF pulses delivered at a rate of 2 Hz for 120 s to produce tissue heated to 38°C), continuous RF (continuous RF currents for 120 s to produce tissue heated to 38°C), or sham treatment (no RF current; electrode maintained in contact with ganglion for 120 s). RESULTS: Treatment with pulsed RF but not continuous RF was associated with a significant increase in the number of cFOS-immunoreactive neurons in the superficial laminae of the dorsal horn as observed 3 hours after treatment. CONCLUSION: Exposure of the dorsal ganglion to pulsed RF currents activates pain-processing neurons in the dorsal horn. This effect is not mediated by tissue heating.

scholarly journals Metastatic renal cell carcinoma mimicking a schwannoma in a dorsal root ganglion: case report

2015 ◽  
Vol 22 (3) ◽  
pp. 314-317 ◽  
Author(s):  
Jason K. Wasserman ◽  
Eve C. Tsai ◽  
Rafael Glikstein ◽  
Kien T. Mai ◽  
Gerard H. Jansen
Keyword(s):  
Renal Cell Carcinoma ◽  
Dorsal Root Ganglion ◽  
Peripheral Nerve ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Dorsal Root ◽  
Metastatic Carcinoma ◽  
The Body ◽  
Peripheral Nerve Involvement

Peripheral nerve tumors are soft-tissue tumors that can occur in any nerve throughout the body. The majority of peripheral nerve tumors arise from elements of the nerve sheath with the two most common being neurofibromas and schwannomas. More than 90% of all peripheral nerve tumors are benign. When there is peripheral nerve involvement in metastatic carcinoma, it is often via contiguous spread from the primary mass; hematogenous seeding to a peripheral nerve is seldom seen. In this report the authors describe the even rarer case of metastatic renal cell carcinoma mimicking a schwannoma in a dorsal root ganglion. Cases from the literature show the rarity of this finding and its late clinical appearance. Given that survival in patients with metastatic carcinoma continues to increase, dorsal root ganglion metastasis may become more common over time.

scholarly journals GPER/β-Alanine Positive Interaction in The Dorsal Root Ganglion Uncovers Potential Mechanisms: Mediating Continuous Neuronal Sensitisation and Neuroinflammation Responses in Neuropathic Pain

2021 ◽  
Author(s):  
Zhenzhen Xu ◽  
Wanli Xie ◽  
Yiqi Feng ◽  
Yanting Wang ◽  
Yuyao He ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Estrogen Receptor ◽  
Neuropathic Pain ◽  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Neuronal Response ◽  
Male Rats ◽  
Patch Clamp Technique ◽  
Positive Interaction ◽  
The Impact

Abstract Background: The pathogenesis of neuropathic pain and the reasons for the prolonged unhealing are still unknown. Increasing evidence suggests that estrogen sex differences play a role in pain sensitivity, but few studies focused on the role of estrogen receptor which maybe an important molecular component contributing to peripheral pain transduction. We aimed to investigate the impact of oestrogen receptors in nociceptive neuronal response in the dorsal root ganglion (DRG) and spinal dorsal horn using a spared nerve injury (SNI) rat model of chronic pain. Methods: We used a class of estrogen receptors antagonists and agonists intrathecal (i.t.) administrated to male rats with SNI or normal rats to identify the main receptor. Moreover, we applied genes identified through genomic metabolic analysis to determine the key metabolism point and elucidate potential mechanisms mediating continuous neuronal sensitisation and neuroinflammation responses in neuropathic pain. The excitability of DRG neurons was detected using the patch clamp technique. Immunohistochemistry, Western blotting, qPCR and behavioral testing were used to assess the expressions, cellular distributions, and actions of main receptor and its related signaling molecules.Results: Increasing the expression and function of G protein-coupled estrogen receptor (GPER), but not estrogen receptor-α (ERα) and estrogen receptor-β (ERβ), in the DRG, but not the dorsal spinal cord, contributed to SNI-induced neuronal sensitisation. Inhibiting GPER expression in the DRG alleviated SNI-induced pain behaviours and neuroinflammation by downregulating IL-1β and IL-6 expression as well as restoring GABAα2 expression simultaneously. Additionally, the positive interaction between GPER and β-alanine, β-alanine accumulation enhances pain sensation and promotes chronic pain development. Conclusion: GPER activation in the DRG causes a positive interaction of β-alanine with IL-1β and IL-6 expression and represses GABAα2 involved in post-SNI neuropathic pain development. Blocking GPER and eliminating β-alanine in the DRG may prevent neuropathic pain development.

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