scholarly journals Sigma-1 Receptor Inhibition Reduces Neuropathic Pain Induced by Partial Sciatic Nerve Transection in Mice by Opioid-Dependent and -Independent Mechanisms

2019 ◽  
Vol 10 ◽  
Author(s):  
Inmaculada Bravo-Caparrós ◽  
Gloria Perazzoli ◽  
Sandra Yeste ◽  
Domagoj Cikes ◽  
José Manuel Baeyens ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Nerve Transection ◽  
Sciatic Nerve Transection ◽  
Sigma 1 Receptor ◽  
Receptor Inhibition ◽  
Sigma 1

scholarly journals Effect of Sciatic Nerve Transection on acetylcholinesterase activity in spinal cord and skeletal muscles of the bullfrog Lithobates catesbeianus

2017 ◽  
Vol 78 (2) ◽  
pp. 217-223
Author(s):  
A. Kroth ◽  
V. Mackedanz ◽  
C. Matté ◽  
A. T. S. Wyse ◽  
M. F. M. Ribeiro ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Skeletal Muscles ◽  
Ache Activity ◽  
Clinical Symptoms ◽  
Phantom Limb ◽  
Nerve Transection ◽  
Sciatic Nerve Transection ◽  
Lithobates Catesbeianus

Abstract Sciatic nerve transection (SNT), a model for studying neuropathic pain, mimics the clinical symptoms of “phantom limb”, a pain condition that arises in humans after amputation or transverse spinal lesions. In some vertebrate tissues, this condition decreases acetylcholinesterase (AChE) activity, the enzyme responsible for fast hydrolysis of released acetylcholine in cholinergic synapses. In spinal cord of frog Rana pipiens, this enzyme’s activity was not significantly changed in the first days following ventral root transection, another model for studying neuropathic pain. An answerable question is whether SNT decreases AChE activity in spinal cord of frog Lithobates catesbeianus, a species that has been used as a model for studying SNT-induced neuropathic pain. Since each animal model has been created with a specific methodology, and the findings tend to vary widely with slight changes in the method used to induce pain, our study assessed AChE activity 3 and 10 days after complete SNT in lumbosacral spinal cord of adult male bullfrog Lithobates catesbeianus. Because there are time scale differences of motor endplate maturation in rat skeletal muscles, our study also measured the AChE activity in bullfrog tibial posticus (a postural muscle) and gastrocnemius (a typical skeletal muscle that is frequently used to study the motor system) muscles. AChE activity did not show significant changes 3 and 10 days following SNT in spinal cord. Also, no significant change occurred in AChE activity in tibial posticus and gastrocnemius muscles at day 3. However, a significant decrease was found at day 10, with reductions of 18% and 20% in tibial posticus and gastrocnemius, respectively. At present we cannot explain this change in AChE activity. While temporally different, the direction of the change was similar to that described for rats. This similarity indicates that bullfrog is a valid model for investigating AChE activity following SNT.

scholarly journals Teneligliptin Exerts Antinociceptive Effects in Rat Model of Partial Sciatic Nerve Transection Induced Neuropathic Pain

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1438
Author(s):  
Yaswanth Kuthati ◽  
Vaikar Navakanth Rao ◽  
Prabhakar Busa ◽  
Chih-Shung Wong
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Acute Pain ◽  
Treatment Options ◽  
Thermal Hyperalgesia ◽  
Tail Flick ◽  
Nerve Transection ◽  
Sciatic Nerve Transection ◽  
Dipeptidyl Peptidase 4 ◽  
Antinociceptive Effects

Neuropathic pain (NP), is a chronic pain resulting from nerve injury, with limited treatment options. Teneligliptin (TEN) is a dipeptidyl peptidase-4 inhibitor (DPP-4i) approved to treat type 2 diabetes. DPP-4is prevent the degradation of the incretin hormone glucagon-like peptide 1 (GLP-1) and prolong its circulation. Apart from glycemic control, GLP-1 is known to have antinociceptive and anti-inflammatory effects. Herein, we investigated the antinociceptive properties of TEN on acute pain, and partial sciatic nerve transection (PSNT)-induced NP in Wistar rats. Seven days post PSNT, allodynia and hyperalgesia were confirmed as NP, and intrathecal (i.t) catheters were implanted and connected to an osmotic pump for the vehicle (1 μL/h) or TEN (5 μg/1 μL/h) or TEN (5 μg) + GLP-1R antagonist Exendin-3 (9–39) amide (EXE) 0.1 μg/1 μL/h infusion. The tail-flick response, mechanical allodynia, and thermal hyperalgesia were measured for 7 more days. On day 14, the dorsal horn was harvested and used for Western blotting and immunofluorescence assays. The results showed that TEN had mild antinociceptive effects against acute pain but remarkable analgesic effects against NP. Furthermore, co-infusion of GLP-1R antagonist EXE with TEN partially reversed allodynia but not tail-flick latency. Immunofluorescence examination of the spinal cord revealed that TEN decreased the immunoreactivity of glial fibrillary acidic protein (GFAP). Taken together, our findings suggest that TEN is efficient in attenuation of PSNT-induced NP. Hence, the pleiotropic effects of TEN open a new avenue for NP management.

scholarly journals Therapeutic effects of peripherally administrated neural crest stem cells on pain and spinal cord changes after sciatic nerve transection

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yang Zhang ◽  
Xiang Xu ◽  
Yuxin Tong ◽  
Xijie Zhou ◽  
Jian Du ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Peripheral Nerve Injury ◽  
Nerve Transection ◽  
Sciatic Nerve Transection ◽  
Neural Crest Stem Cells ◽  
Function Recovery

Abstract Background Severe peripheral nerve injury significantly affects patients’ quality of life and induces neuropathic pain. Neural crest stem cells (NCSCs) exhibit several attractive characteristics for cell-based therapies following peripheral nerve injury. Here, we investigate the therapeutic effect of NCSC therapy and associated changes in the spinal cord in a sciatic nerve transection (SNT) model. Methods Complex sciatic nerve gap injuries in rats were repaired with cell-free and cell-laden nerve scaffolds for 12 weeks (scaffold and NCSC groups, respectively). Catwalk gait analysis was used to assess the motor function recovery. The mechanical withdrawal threshold and thermal withdrawal latency were used to assess the development of neuropathic pain. Activation of glial cells was examined by immunofluorescence analyses. Spinal levels of extracellular signal-regulated kinase (ERK), NF-κB P65, brain-derived neurotrophic factor (BDNF), growth-associated protein (GAP)-43, calcitonin gene-related peptide (CGRP), and inflammation factors were calculated by western blot analysis. Results Catwalk gait analysis showed that animals in the NCSC group exhibited a higher stand index and Max intensity At (%) relative to those that received the cell-free scaffold (scaffold group) (p < 0.05). The mechanical and thermal allodynia in the medial-plantar surface of the ipsilateral hind paw were significantly relieved in the NCSC group. Sunitinib (SNT)-induced upregulation of glial fibrillary acidic protein (GFAP) (astrocyte) and ionized calcium-binding adaptor molecule 1 (Iba-1) (microglia) in the ipsilateral L4–5 dorsal and ventral horn relative to the contralateral side. Immunofluorescence analyses revealed decreased astrocyte and microglia activation. Activation of ERK and NF-κB signals and expression of transient receptor potential vanilloid 1 (TRPV1) expression were downregulated. Conclusion NCSC-laden nerve scaffolds mitigated SNT-induced neuropathic pain and improved motor function recovery after sciatic nerve repair. NCSCs also protected the spinal cord from SNT-induced glial activation and central sensitization.

Local Nogo-66 administration reduces neuropathic pain after sciatic nerve transection in rat

2007 ◽  
Vol 424 (3) ◽  
pp. 145-148 ◽  
Author(s):  
Lihong Li ◽  
Huaizhou Qin ◽  
Weiqi Shi ◽  
Guodong Gao
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Nerve Transection ◽  
Sciatic Nerve Transection

scholarly journals Baicalein attenuates neuropathic pain and improves sciatic nerve function recovery in rats with partial sciatic nerve transection

2018 ◽  
Vol 81 (11) ◽  
pp. 955-963 ◽  
Author(s):  
Hou-Chuan Lai ◽  
Chueng-He Lu ◽  
Chih-Shung Wong ◽  
Bo-Feng Lin ◽  
Shun-Ming Chan ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Nerve Function ◽  
Nerve Transection ◽  
Sciatic Nerve Transection ◽  
Function Recovery

scholarly journals The σ1 Receptor and the HINT1 Protein Control α2δ1 Binding to Glutamate NMDA Receptors: Implications in Neuropathic Pain

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1681
Author(s):  
María Rodríguez-Muñoz ◽  
Elsa Cortés-Montero ◽  
Yara Onetti ◽  
Pilar Sánchez-Blázquez ◽  
Javier Garzón-Niño
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Mechanical Allodynia ◽  
Chronic Constriction Injury ◽  
Intracerebroventricular Injection ◽  
Sigma 1 Receptor ◽  
Targeted Deletion ◽  
Σ1 Receptor ◽  
Sigma 1 ◽  
Glutamate Nmda Receptors

Nerve injury produces neuropathic pain through the binding of α2δ1 proteins to glutamate N-methyl-D-aspartate receptors (NMDARs). Notably, mice with a targeted deletion of the sigma 1 receptor (σ1R) gene do not develop neuropathy, whereas mice lacking the histidine triad nucleotide-binding protein 1 (Hint1) gene exhibit exacerbated allodynia. σ1R antagonists more effectively diminish neuropathic pain of spinal origin when administered by intracerebroventricular injection than systemically. Thus, in mice subjected to unilateral sciatic nerve chronic constriction injury (CCI), we studied the participation of σ1Rs and HINT1 proteins in the formation of α2δ1-NMDAR complexes within the supraspinal periaqueductal gray (PAG). We found that δ1 peptides required σ1Rs in order to interact with the NMDAR NR1 variant that contains the cytosolic C1 segment. σ1R antagonists or low calcium levels provoke the dissociation of σ1R-NR1 C1 dimers, while they barely affect the integrity of δ1-σ1R-NR1 C1 trimers. However, HINT1 does remove δ1 peptides from the trimer, thereby facilitating the subsequent dissociation of σ1Rs from NMDARs. In σ1R-/- mice, CCI does not promote the formation of NMDAR-α2δ1 complexes and allodynia does not develop. The levels of α2δ1-σ1R-NMDAR complexes increase in HINT1-/- mice and after inducing CCI, degradation of α2δ1 proteins is observed. Notably, σ1R antagonists but not gabapentinoids alleviate neuropathic pain in these mice. During severe neuropathy, the metabolism of α2δ1 proteins may account for the failure of many patients to respond to gabapentinoids. Therefore, σ1Rs promote and HINT1 proteins hinder the formation α2δ1-NMDAR complexes in the PAG, and hence, the appearance of mechanical allodynia depends on the interplay between these proteins.

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