Differential anti-neuropathic pain effects of tetrodotoxin in sciatic nerve- versus infraorbital nerve-ligated rats – Behavioral, pharmacological and immunohistochemical investigations

Background: Modern research on peripheral neuropathy circumstance utter that treatments with Vincristine (VCR) disturb the microtubular cells in sensory and motor neurons due to calcium over- load in sciatic nerve, unfortunately, VCR triggering the release of Tumor necrosis factor-α (TNFα) in central neurons causes excitotoxicity as well. Although ethnomedical information specifies that Pterocarpus marsupium Roxb (PM) is widely used for various nervous disorders, not yet justified on VCR induced peripheral neuropathy and in relation to central mechanism. Objective: This study is aimed to explore the possible central and peripheral mechanism of flavonoid enriched PM in VCR induced neuropathy model. Methods: Neuropathic pain was induced in female Wistar rats by VCR (75μg/ kg/day, i.p) for 10 days. Nociceptive thresholds were assessed by subjecting them to behavioral and biochemical estimation, proinflammatory cytokines along with morphological evaluation. Results: PM significantly increased the nociceptive threshold evident from various behavioral models in comparison to VCR group. More importantly, PM significantly reversed the VCR induced calcium elevation, glutamate and aspartate release in the brain. Discussion: It was also observed that the raised TNF-α, Interleukin-1β were controlled and interleukin- 10 was elevated in sciatic nerve after PM treatment. Evident from histology, PM markedly reversed the VCR induced axonal degeneration, Schwann cell hyperplasia, and myelin fibrosis. Conclusion: Flavonoid enriched PM both 100 & 200mg/kg post and co-administration exerted a preventive and curative effect in VCR induced neuropathic pain by controlling calcium-mediated excitotoxicity through peripheral and central mechanism.

Download Full-text

Alpha lipoic acid attenuated neuropathic pain induced by chronic constriction Injury of sciatic nerve in rats

Clinical Phytoscience ◽

10.1186/s40816-021-00263-7 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Prasad Neerati ◽

Harika Prathapagiri

Keyword(s):

Neuropathic Pain ◽

Peripheral Neuropathy ◽

Sciatic Nerve ◽

Lipoic Acid ◽

Normal Saline ◽

Chronic Constriction Injury ◽

Thermal Hyperalgesia ◽

Alpha Lipoic Acid ◽

Chronic Neuropathic Pain ◽

Neuropathic Pain Syndrome

Abstract Background Chronic neuropathic pain syndrome is associated with impaired quality of life and is poorly manageable. Alpha lipoic acid (ALA) is a powerful antioxidant and showed its effectiveness on diabetic neuropathy and other acute peripheral nerve injuries but it was not evaluated in the chronic neuropathic pain, chronic constriction injury (CCI) in rat model by using duloxetine (DLX) as standard. Methodology The main objective of the study was to expedite ALA effect on chronic peripheral neuropathy induced by CCI of sciatic nerve in rats. In this study, male Wister rats were randomly divided into six groups (n = 8) including, normal saline, sham operated, surgery control, DLX 30mg/kg treated, ALA treated 25mg/kg, and ALA+DLX. The CCI of sciatic nerve was conducted on all animals except normal saline group and studied for 21 days (i.e. 14 days treatment period & 7 days treatment free period) by using different behavioral, biochemical and, histopathology studies. Results ALA showed minor but significant decrease of thermal hyperalgesia, cold allodynia, malondialdehyde (MDA), total protein, lipid peroxidation, and nitric oxide levels and significant increase of motor coordination, glutathione level and decreased axonal degeneration significantly. These effects sustained even during treatment free period. ALA enhanced the effect of DLX when given in combination by showing sustained effect. In conclusion, ALA acted as potent antioxidant may be this activity is responsible for the potent neuroprotective effect. Conclusion Hence, ALA attenuated the nueroinflammation mediated by chronic peripheral neuropathy. Further studies are warranted with ALA to develop as a clinically relevant therapeutic agent for the treatment of neuropathic pain.

Download Full-text

SUR1, newly expressed in astrocytes, mediates neuropathic pain in a mouse model of peripheral nerve injury

Molecular Pain ◽

10.1177/17448069211006603 ◽

2021 ◽

Vol 17 ◽

pp. 174480692110066

Author(s):

Orest Tsymbalyuk ◽

Volodymyr Gerzanich ◽

Aaida Mumtaz ◽

Sanketh Andhavarapu ◽

Svetlana Ivanova ◽

...

Keyword(s):

Spinal Cord ◽

Neuropathic Pain ◽

Sciatic Nerve ◽

Peripheral Nerve ◽

Dorsal Horn ◽

Nerve Injury ◽

Peripheral Nerve Injury ◽

Thermal Sensitivity ◽

Gradual Improvement ◽

Pain Behaviors

Background Neuropathic pain following peripheral nerve injury (PNI) is linked to neuroinflammation in the spinal cord marked by astrocyte activation and upregulation of interleukin 6 (IL -6 ), chemokine (C-C motif) ligand 2 (CCL2) and chemokine (C-X-C motif) ligand 1 (CXCL1), with inhibition of each individually being beneficial in pain models. Methods Wild type (WT) mice and mice with global or pGfap-cre- or pGFAP-cre/ERT2-driven Abcc8/SUR1 deletion or global Trpm4 deletion underwent unilateral sciatic nerve cuffing. WT mice received prophylactic (starting on post-operative day [pod]-0) or therapeutic (starting on pod-21) administration of the SUR1 antagonist, glibenclamide (10 µg IP) daily. We measured mechanical and thermal sensitivity using von Frey filaments and an automated Hargreaves method. Spinal cord tissues were evaluated for SUR1-TRPM4, IL-6, CCL2 and CXCL1. Results Sciatic nerve cuffing in WT mice resulted in pain behaviors (mechanical allodynia, thermal hyperalgesia) and newly upregulated SUR1-TRPM4 in dorsal horn astrocytes. Global and pGfap-cre-driven Abcc8 deletion and global Trpm4 deletion prevented development of pain behaviors. In mice with Abcc8 deletion regulated by pGFAP-cre/ERT2, after pain behaviors were established, delayed silencing of Abcc8 by tamoxifen resulted in gradual improvement over the next 14 days. After PNI, leakage of the blood-spinal barrier allowed entry of glibenclamide into the affected dorsal horn. Daily repeated administration of glibenclamide, both prophylactically and after allodynia was established, prevented or reduced allodynia. The salutary effects of glibenclamide on pain behaviors correlated with reduced expression of IL-6, CCL2 and CXCL1 by dorsal horn astrocytes. Conclusion SUR1-TRPM4 may represent a novel non-addicting target for neuropathic pain.

Download Full-text

Incidence, Aetiology, and Associated Fracture Patterns of Infraorbital Nerve Injuries Following Zygomaticomaxillary Complex Fractures: A Retrospective Analysis of 272 Patients

Craniomaxillofacial Trauma & Reconstruction ◽

10.1177/19433875211022569 ◽

2021 ◽

pp. 194338752110225

Author(s):

Kathia Dubron ◽

Maarten Verbist ◽

Eman Shaheen ◽

Titiaan Jacob Dormaar ◽

Reinhilde Jacobs ◽

...

Keyword(s):

Neuropathic Pain ◽

Interpersonal Violence ◽

Fracture Line ◽

Infraorbital Nerve ◽

Type B ◽

Treatment Methods ◽

Infraorbital Canal ◽

Pain Symptoms ◽

Fracture Types ◽

Zygomaticomaxillary Complex

Study Design: Retrospective study. Objective: Zygomaticomaxillary complex (ZMC) fractures are common facial injuries with heterogeneity regarding aetiologies, fracture types, infraorbital nerve (ION) involvement, and treatment methods. The aim of this study was to identify associations between aetiologies, fracture types, and neurological complications. Additionally, treatment methods and recovery time were investigated. Methods: Medical files of 272 patients with unilateral and bilateral ZMC fractures were reviewed, whose cases were managed from January 2014 to January 2019 at the Department of Oral and Maxillofacial Surgery, University hospitals Leuven, Belgium. History of ION sensory dysfunction and facial nerve motoric dysfunction were noted during follow-up. Results: ION hypoaesthesia incidence was 37.3%, with the main causes being fall accidents, road traffic accidents, and interpersonal violence. Significant predictors of ION hypoaesthesia were Zingg type B fractures ( P = 0.003), fracture line course through the infraorbital canal ( P < .001), orbital floor fracture ( P < 0.001), and ZMC dislocation or mobility ( P = 0.001). Conclusion: Of all ZMC fractures, 37.3% exhibited ION hypoaesthesia. Only ZMC Zingg type B fractures (74.0%) were significantly more associated with ION hypoaesthesia. ION hypoesthesia was more likely (OR = 2.707) when the fracture line course ran through the infraorbital canal, and was less dependent on the degree of displacement. Neuropathic pain symptoms developed after ZMC fractures in 2.2% patients, posing a treatment challenge. Neuropathic pain symptoms were slightly more common among women, and were associated only with type B or C fractures. No other parameters were found to predict the outcome of this post-traumatic neuropathic pain condition.

Download Full-text

Prevention of painful neuromas by oblique transection of peripheral nerves

Journal of Neurosurgery ◽

10.3171/jns.2006.104.2.285 ◽

2006 ◽

Vol 104 (2) ◽

pp. 285-289 ◽

Cited By ~ 18

Author(s):

Wieslaw Marcol ◽

Katarzyna Kotulska ◽

Magdalena Larysz-Brysz ◽

Grazyna Bierzyñska-Macyszyn ◽

Pawel Wlaszczuk ◽

...

Keyword(s):

Neuropathic Pain ◽

Sciatic Nerve ◽

Peripheral Nerves ◽

Traditional Method ◽

Healing Process ◽

Nerve Transection ◽

Proximal Stump ◽

Sciatic Nerves ◽

Neuroma Formation

Object Neuroma formation often occurs at the proximal stump of the transected nerve, complicating the healing process after gap injuries or nerve biopsies. Most such neuromas cause therapy-resistant neuropathic pain. The purpose of this study was to determine whether oblique transection of the proximal stump of the sciatic nerve can prevent neuroma formation. Methods The sciatic nerves of 10 rats were transected unilaterally at an angle of 30°, and the peripheral segments of the nerves were removed. In 10 control animals the sciatic nerves were transected at a perpendicular angle. Twenty weeks after surgery the nerves were reexposed and collected. The presence of neuromas was determined by two board-certified pathologists on the basis of histopathological evaluations. Conclusions The oblique transection of peripheral nerves, contrary to perpendicularly transected nerves, is rarely followed by classic neuroma development. Moreover, neuropathic pain is significantly reduced compared with that following the traditional method of nerve transection.

Download Full-text

Effects of 660- and 980-nm low-level laser therapy on neuropathic pain relief following chronic constriction injury in rat sciatic nerve

Lasers in Medical Science ◽

10.1007/s10103-014-1552-1 ◽

2014 ◽

Vol 29 (5) ◽

pp. 1593-1598 ◽

Cited By ~ 33

Author(s):

M. Masoumipoor ◽

S. B. Jameie ◽

A. Janzadeh ◽

F. Nasirinezhad ◽

M. Soleimani ◽

...

Keyword(s):

Neuropathic Pain ◽

Pain Relief ◽

Sciatic Nerve ◽

Laser Therapy ◽

Chronic Constriction Injury ◽

Low Level Laser Therapy ◽

Low Level ◽

Rat Sciatic Nerve ◽

Low Level Laser ◽

Level Laser

Download Full-text

Involvement of protein isoprenylation in neuropathic pain induced by sciatic nerve injury in mice

Neuroscience Letters ◽

10.1016/j.neulet.2014.01.039 ◽

2014 ◽

Vol 564 ◽

pp. 27-31 ◽

Cited By ~ 2

Author(s):

Masahiro Ohsawa ◽

Junpei Mutoh ◽

Shohei Yamamoto ◽

Hiroaki Hisa

Keyword(s):

Neuropathic Pain ◽

Sciatic Nerve ◽

Nerve Injury ◽

Sciatic Nerve Injury ◽

Protein Isoprenylation

Download Full-text

Preemptive analgesic effect of lidocaine in a chronic neuropathic pain model

Arquivos de Neuro-Psiquiatria ◽

10.1590/s0004-282x2009000600024 ◽

2009 ◽

Vol 67 (4) ◽

pp. 1088-1092 ◽

Cited By ~ 6

Author(s):

Leonardo M. Batista ◽

Igor M. Batista ◽

João P. Almeida ◽

Carlos H. Carvalho ◽

Samuel B. de Castro-Costa ◽

...

Keyword(s):

Neuropathic Pain ◽

Sciatic Nerve ◽

Control Group ◽

Thermal Stimulus ◽

Lidocaine Group ◽

Local Infiltration ◽

Neuropathic Pain Model ◽

Group 3 ◽

Group 2 ◽

The Right

Preemptive analgesia inhibits the progression of pain caused by surgical lesions. To analyze the effect of lidocaine on postoperative pain relief, we performed compression of the right sciatic nerve in Wistar rats and observed the differences on behavior between the group that received lidocaine and the group that was not treated with the local anesthetics pre-operatively. Group 1 was not operated (control); group 2 underwent the sciatic nerve ligature without lidocaine; group 3, underwent surgery with previous local infiltration of lidocaine. Group 2 showed significantly longer scratching times with a peak on day 14 post-operative (p=0.0005) and reduction in the latency to both noxious (p=0.003) and non-noxious (p=0.004) thermal stimulus. Group 3 presented significantly shorter scratching times (p=0.004) and longer latency times when compared to Group 2. Preemptive use of lidocaine 2% can potentially reduce the postoperative neuropathic pain associated with sciatic nerve compression.

Download Full-text