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Experimental Characterization of the Chronic Constriction Injury-Induced Neuropathic Pain Model in Mice

Gopalsamy B, Sambasevam Y, Zulazmi NA, Chia JSM, Omar Farouk AA, Sulaiman MR, et al.

Neurochem Res, 2019 Sep;44(9):2123-2138.
PMID: 31376053 DOI: 10.1007/s11064-019-02850-0

Number of ligations made in the chronic constriction injury (CCI) neuropathic pain model has raised serious concerns. We compared behavioural responses, nerve morphology and expression of pain marker, c-fos among CCI models developed with one, two, three and four ligations. The numbers of ligation(s) on sciatic nerve shows no significant difference in displaying mechanical and cold allodynia, and mechanical and thermal hyperalgesia throughout 84 days. All groups underwent similar levels of nerve degeneration post-surgery. Similar c-fos level in brain cingulate cortex, parafascicular nuclei and amygdala were observed in all CCI models compared to sham-operated group. Therefore, number of ligations does not impact intensity of pain symptoms, pathogenesis and neuronal activation. A single ligation is sufficient to develop neuropathic pain, in contrast to the established model of four ligations. This study dissects and characterises the CCI model, ascertaining a more uniform animal model to surrogate actual neuropathic pain condition.

Matched MeSH terms: Sciatic Neuropathy/etiology; Sciatic Neuropathy/metabolism; Sciatic Neuropathy/pathology; Sciatic Neuropathy/physiopathology
A comparison between the effects of three potential scar-reducing agents applied at a site of sciatic nerve repair

Ngeow WC, Atkins S, Morgan CR, Metcalfe AD, Boissonade FM, Loescher AR, et al.

Neuroscience, 2011 May 5;181:271-7.
PMID: 21377512 DOI: 10.1016/j.neuroscience.2011.02.054

We have investigated the effect of three potential scar-reducing agents applied at a sciatic nerve repair site in C57-black-6 mice. Under anaesthesia the nerve was transected, repaired using four epineurial sutures, and 100 μl of either triamcinolone acetonide (1 mg/100 μl), an interleukin-10 peptide fragment (125 ng/100 μl or 500 ng/100 μl) or mannose-6-phosphate (M6P, 200 mM or 600 mM) was injected into and around the nerve. After 6 weeks the extent of regeneration was assessed electrophysiologically by determining the ratio of the compound action potential (CAP) modulus evoked by electrical stimulation of the nerve 2 mm distal or proximal to the repair site. The conduction velocity of the fastest components in the CAP was also calculated. The percentage area of collagen staining (PAS) at the repair site was analysed using Picrosirius Red and image analysis. Comparisons were made with a placebo group (100 μl of phosphate buffered saline) and sham-operated controls. The median CAP modulus ratio in the 600 mM M6P group was 0.44, which was significantly higher than in the placebo group (0.24, P=0.012: Kruskal-Wallis test). Conduction velocities were also faster in the 600 mM M6P group (median 30 m s(-1)) than in the placebo group (median 27.8 m s(-1); P=0.0197: Kruskal-Wallis test). None of the other treated groups were significantly different from the placebo, and all had significantly lower CAP ratios than the sham controls (P<0.05). All repair groups had a significantly higher PAS for collagen than sham controls. We conclude that the administration of 600 mM mannose-6-phosphate to a nerve repair site enhances axonal regeneration.

Matched MeSH terms: Sciatic Neuropathy/drug therapy*; Sciatic Neuropathy/pathology; Sciatic Neuropathy/physiopathology
Delayed Onset Sciatic Nerve Palsy Secondary to Wound Hematoma following Anticoagulant Therapy Post-Bipolar Hemiarthroplasty - an Uncommon Complication: A Case Report

Balaji G, Sriharsha Y, Sharma D

Malays Orthop J, 2019 Jul;13(2):49-51.
PMID: 31467653 DOI: 10.5704/MOJ.1907.010

A 58-year old female patient presented to us with a three months' old fracture of the neck of femur. She underwent bipolar hemiarthroplasty. In the immediate postoperative period, she developed deep vein thrombosis for which she was started on anticoagulant therapy. Patient had persistent discharge from the wound since then and underwent regular dressings. On the eighth post-op day, she developed sciatic nerve palsy secondary to wound haematoma. The haematoma was decompressed immediately and she had a dramatic improvement in pain but her neurological deficit persisted. The wound healed completely without any complications. At three months follow up, she had recovered completely with grade 5/5 power in ankle and foot and full sensory recovery in the sciatic nerve distribution. She was ambulating comfortably with a walker. At final follow up around 20 months post-operation, she was pain-free and walking without any support. The wound had healed completely.

Matched MeSH terms: Sciatic Neuropathy
Fulltext Effect of tocotrienol rich fraction (TRF) on muscles reinnervation after sciatic nerve crush injury in rats

Amalia Lailanor, Nurul Alaina Hj Yahya, Junedah Sanusi, Huzwah Khaza’ai, Muhammad Danial Che Ramli

Malaysian Journal of Medicine and Health Sciences, 2020;16(101):118-124.
MyJurnal

Introduction: Muscle denervation is a process where muscles lose nerve supply due to neural damage and this may lead to paralysis in human. Muscle denervation is mainly caused by peripheral nerve injuries especially in the lower extremities that resulted in devastating effect on human daily functions and routines. Tocotrienol Rich Fraction (TRF) consist of 75% of tocotrienols have shown potential neuroprotective properties. The objective of this study is to ob- serve motor coordination and histological characteristics on muscles that underwent sciatic nerve crush injury and supplemented with TRF. Methods: A total of 104 Sprague-Dawley rats were divided into four groups; normal group (n=8) with no sciatic nerve crush injury, negative control (n=32) with sciatic nerve crush injury at hindlimb without treatment, positive control (n=32) sciatic nerve crush injury treated with 500 µg/kg/day of methylcobalamin, and experimental group (n=32) of rats that underwent sciatic nerve crush injury and treated with 200 mg/kg/day of TRF. Result: Skeletal muscles which located at hind limb; Soleus Muscle and Extenstor Digitorum Longus Muscle (EDL) muscle have shown an increasing in weight when it is supplemented with TRF 200 mg/kg/day and improved myelin layer of nerve. Conclusion: This study showed that TRF has the potency to improve reinnervation rate and neuron supply in hind muscle.

Matched MeSH terms: Sciatic Neuropathy
Fulltext Centella asiatica (L.)-Neurodifferentiated Mesenchymal Stem Cells Promote the Regeneration of Peripheral Nerve

Hussin HM, Lawi MM, Haflah NHM, Kassim AYM, Idrus RBH, Lokanathan Y

Tissue Eng Regen Med, 2020 04;17(2):237-251.
PMID: 32036567 DOI: 10.1007/s13770-019-00235-6

BACKGROUND: Centella asiatica (L.) is a plant with neuroprotective and neuroregenerative properties; however, its effects on the neurodifferentiation of mesenchymal stem cells (MSCs) and on peripheral nerve injury are poorly explored. This study aimed to investigate the effects of C. asiatica (L.)-neurodifferentiated MSCs on the regeneration of peripheral nerve in a critical-size defect animal model.
METHODS: Nerve conduit was developed using decellularised artery seeded with C. asiatica-neurodifferentiated MSCs (ndMSCs). A 1.5 cm sciatic nerve injury in Sprague-Dawley rat was bridged with reversed autograft (RA) (n = 3, the gold standard treatment), MSC-seeded conduit (MC) (n = 4) or ndMSC-seeded conduit (NC) (n = 4). Pinch test and nerve conduction study were performed every 2 weeks for a total of 12 weeks. At the 12th week, the conduits were examined by histology and transmission electron microscopy.
RESULTS: NC implantation improved the rats' sensory sensitivity in a similar manner to RA. At the 12th week, nerve conduction velocity was the highest in NC compared with that of RA and MC. Axonal regeneration was enhanced in NC and RA as shown by the expression of myelin basic protein (MBP). The average number of myelinated axons was significantly higher in NC than in MC but significantly lower than in RA. The myelin sheath thickness was higher in NC than in MC but lower than in RA.
CONCLUSION: NC showed promising effects on nerve regeneration and functional restoration similar to those of RA. These findings revealed the neuroregenerative properties of C. asiatica and its potential as an alternative strategy for the treatment of critical size nerve defect.

Matched MeSH terms: Sciatic Neuropathy
Fulltext Sodium phenylbutyrate inhibits Schwann cell inflammation via HDAC and NFκB to promote axonal regeneration and remyelination

Yadav A, Huang TC, Chen SH, Ramasamy TS, Hsueh YY, Lin SP, et al.

J Neuroinflammation, 2021 Oct 16;18(1):238.
PMID: 34656124 DOI: 10.1186/s12974-021-02273-1

BACKGROUND: Epigenetic regulation by histone deacetylases (HDACs) in Schwann cells (SCs) after injury facilitates them to undergo de- and redifferentiation processes necessary to support various stages of nerve repair. Although de-differentiation activates the synthesis and secretion of inflammatory cytokines by SCs to initiate an immune response during nerve repair, changes in either the timing or duration of prolonged inflammation mediated by SCs can affect later processes associated with repair and regeneration. Limited studies have investigated the regulatory processes through which HDACs in SCs control inflammatory cytokines to provide a favorable environment for peripheral nerve regeneration.
METHODS: We employed the HDAC inhibitor (HDACi) sodium phenylbutyrate (PBA) to address this question in an in vitro RT4 SC inflammation model and an in vivo sciatic nerve transection injury model to examine the effects of HDAC inhibition on the expression of pro-inflammatory cytokines. Furthermore, we assessed the outcomes of suppression of extended inflammation on the regenerative potential of nerves by assessing axonal regeneration, remyelination, and reinnervation.
RESULTS: Significant reductions in lipopolysaccharide (LPS)-induced pro-inflammatory cytokine (tumor necrosis factor-α [TNFα]) expression and secretion were observed in vitro following PBA treatment. PBA treatment also affected the transient changes in nuclear factor κB (NFκB)-p65 phosphorylation and translocation in response to LPS induction in RT4 SCs. Similarly, PBA mediated long-term suppressive effects on HDAC3 expression and activity. PBA administration resulted in marked inhibition of pro-inflammatory cytokine secretion at the site of transection injury when compared with that in the hydrogel control group at 6-week post-injury. A conducive microenvironment for axonal regrowth and remyelination was generated by increasing expression levels of protein gene product 9.5 (PGP9.5) and myelin basic protein (MBP) in regenerating nerve tissues. PBA administration increased the relative gastrocnemius muscle weight percentage and maintained the intactness of muscle bundles when compared with those in the hydrogel control group.
CONCLUSIONS: Suppressing the lengthened state of inflammation using PBA treatment favors axonal regrowth and remyelination following nerve transection injury. PBA treatment also regulates pro-inflammatory cytokine expression by inhibiting the transcriptional activation of NFκB-p65 and HDAC3 in SCs in vitro.

Matched MeSH terms: Sciatic Neuropathy