Postoperative pain and morphine consumption after ultrasound-guided femoral and sciatic combined nerve block versus neurostimulation for femoral and sciatic combined nerve block or neurostimulation for femoral nerve block in primary elective total knee arthroplasty.

Abstract Congreso XXXVII National Meeting of the Spanish Society of Pharmacology with guest society: The British Pharmacological SocietyBackground and Aims: Total knee arthroplasty injuries are extremely painful and merit prompt attention to adequate postoperative analgesia. We aim to compare femoral and sciatic ultrasound-guided combined nerve block vs. neurostimulation for femoral and sciatic combined nerve block or for femoral nerve block in postoperative pain in primary elective total knee prosthesis. Summary of work and outcomes: A three arms, prospective longitudinal study of patients having primary elective unilateral knee prosthesis and randomly assigned to catheter insertion guided by ultrasound or neurostimulation was done: 1) Ultrasound-guided femoral and sciatic combined nerve block (USFSCN) (N=15); 2) Neurostimulation for femoral and sciatic combined nerve block (NSFSCN) (N=17); 3) Neurostimulation for femoral nerve block (NSFN) (N=11). Total analgesia (morphine) consumption after 48 hours was the primary endpoint. The postoperative pain intensity (visual analogue pain scale (VAS)) at post-anaesthetic recovery unit (PARU), 6, 24, 48 h, and during movement and postoperative complications were secondary outcomes. Results and discussion: 43 patients (68.3±8 years old, 77% female) subjected to elective unilateral knee prosthesis were enrolled. There were no differences in the demographic, anaesthetic and surgical variables between groups. Pain intensity was lower in the USFSCN group compared with NSFSCN and NSFN during the first 48 h post-surgery (% of intense pain at PARU/6h/24h/48h): USFSCN 0.8/1.4/3.2/1.6; NSFSCN 5.6/8.3/7.5/3; NSFN 7.2/5.3/6.4/5.4. The average consumption of morphine within 48 h after surgery was similar in the groups USFSCN and NSFSCN (3 mg vs. 3.11 mg), and significantly lower than NSFN (4.19 mg) (p<0.05). And the number of complications was significantly lower in the USFSCN group compared with NSFSCN and NSFN during the first 48 h of postoperative. Conclusion: Ultrasound-guided femoral and sciatic combined nerve block presented better analgesia and was more safety than neurostimulation for femoral and sciatic combined nerve block or for femoral nerve block in primary elective total knee arthroplasty.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Ultrasound-Guided Femoral and Sciatic Nerve Blocks for Repair of Tibia and Fibula Fractures in a Bennett's Wallaby (Macropus rufogriseus)

Locoregional anesthetic techniques may be a very useful tool for the anesthetic management of wallabies with injuries of the pelvic limbs and may help to prevent capture myopathies resulting from stress and systemic opioids’ administration. This report describes the use of ultrasound-guided femoral and sciatic nerve blocks in Bennett’s wallaby (Macropus rufogriseus) referred for orthopaedic surgery. Ultrasound-guided femoral and sciatic nerve blocks were attempted at the femoral triangle and proximal thigh level, respectively. Whilst the sciatic nerve could be easily visualised, the femoral nerve could not be readily identified. Only the sciatic nerve was therefore blocked with ropivacaine, and methadone was administered as rescue analgesic. The ultrasound images were stored and sent for external review. Anesthesia and recovery were uneventful and the wallaby was discharged two days postoperatively. At the time of writing, it is challenging to provide safe and effective analgesia to Macropods. Detailed knowledge of the anatomy of these species is at the basis of successful locoregional anesthesia. The development of novel analgesic techniques suitable for wallabies would represent an important step forward in this field and help the clinicians dealing with these species to improve their perianesthetic management

The effect of vascular graft and human umbilical cord blood-derived CD34+ stem cell on peripheral nerve healing

AIM: There are many trials concerning peripheral nerve damage causes and treatment options. Unfortunately, nerve damage is still a major problem regarding health, social and economic issues. On this study, we used vascular graft and human cord blood derived stem cells to find an alternative treatment solution to this problem. MATERIAL AND METHODS: We used 21 female Wistar rats on our study. They were anesthetized with ketamine and we studied right hind limbs. On Group 1, we did a full layer cut on the right sciatic nerve. On Group 2, we did a full layer cut on the right sciatic nerve, and we covered synthetic vascular graft on cut area. On Group 3, we did a full layer cut on right sciatic nerve, and we covered the area with stem cell applied vascular graft. RESULTS: At the end of postoperative 8. weeks, we performed EMG on the rats. When we compared healthy and degenerated areas as a result of EMG, we found significant amplitude differences between the groups on healthy areas whereas there was no significant difference on degenerated areas between the groups. Then we re-opened the operated area again to reveal the sciatic nerve cut area, and we performed electron microscope evaluation. On the stem cell group, we observed that both the axon and the myelin sheet prevented degeneration. CONCLUSION: This study is a first on using synthetic vascular graft and cord blood derived CD34+ cells in peripheral nerve degeneration. On the tissues that were examined with electron microscope, we observed that CD34+ cells prevented both axonal and myelin sheath degeneration. Nerve tissue showed similar results to the control group, and the damage was minimal. © 2018 Ali Yilmaz, Abdullah Topcu, Cagdas Erdogan, Levent Sinan Bir, Barbaros Sahin, Gulcin Abban, Erdal Coskun, Ayca Ozkul

Sciatic neuropathy with preserved sensory nerve action potentials, a case series

Background: Sciatic neuropathy is differentiated from lumbosacral radiculopathy based on the finding of abnormal sensory nerve action potentials (SNAPs). Cases of sciatic neuropathy with intact SNAPS have not been well described. Methods: A retrospective analysis of 12 patients with sciatic neuropathy in a single institution. Results: We describe 12 patients in whom a sciatic neuropathy was diagnosed based on a combination of history, physical exam, radiological and electrodiagnostic (EDX) findings. Lower extremity SNAPs were found to be within normal range in all patients, although SNAP amplitude asymmetry between both sides was observed in 3. Included patients were young (mean age of 40.3 years) and mostly female (9 patients). Conclusions: Sciatic neuropathy may occur with a relative sparing of sensory fibers. Recognition of this group of patients should help to avoid making a misdiagnosis of lumbosacral radiculopathy

Nlrp6 promotes recovery after peripheral nerve injury independently of inflammasomes

Background: NOD-like receptors (Nlrs) are key regulators of immune responses during infection and autoimmunity. A subset of Nlrs assembles inflammasomes, molecular platforms that are activated in response to endogenous danger and microbial ligands and that control release of interleukin (IL)-1 beta and IL-18. However, their role in response to injury in the nervous system is less understood. Methods: In this study, we investigated the expression profile of major inflammasome components in the peripheral nervous system (PNS) and explored the physiological role of different Nlrs upon acute nerve injury in mice. Results: While in basal conditions, predominantly members of NOD-like receptor B (Nlrb) subfamily (NLR family, apoptosis inhibitory proteins (NAIPs)) and Nlrc subfamily (ICE-protease activating factor (IPAF)/NOD) are detected in the sciatic nerve, injury causes a shift towards expression of the Nlrp family. Sterile nerve injury also leads to an increase in expression of the Nlrb subfamily, while bacteria trigger expression of the Nlrc subfamily. Interestingly, loss of Nlrp6 led to strongly impaired nerve function upon nerve crush. Loss of the inflammasome adaptor apoptosis-associated speck-like protein containing a CARD (ASC) and effector caspase-1 and caspase-11 did not affect sciatic nerve function, suggesting that Nlrp6 contributed to recovery after peripheral nerve injury independently of inflammasomes. In line with this, we did not detect release of mature IL-1 beta upon acute nerve injury despite potent induction of pro-IL-1 beta and inflammasome components Nlrp3 and Nlrp1. However, Nlrp6 deficiency was associated with increased pro-inflammatory extracellular regulated MAP kinase (ERK) signaling, suggesting that hyperinflammation in the absence of Nlrp6 exacerbated peripheral nerve injury. Conclusions: Together, our observations suggest that Nlrp6 contributes to recovery from peripheral nerve injury by dampening inflammatory responses independently of IL-1 beta and inflammasomes

ATF3 upregulation in glia during Wallerian degeneration: differential expression in peripheral nerves and CNS white matter

Background: Many changes in gene expression occur in distal stumps of injured nerves but the transcriptional control of these events is poorly understood. We have examined the expression of the transcription factors ATF3 and c-Jun by non-neuronal cells during Wallerian degeneration following injury to sciatic nerves, dorsal roots and optic nerves of rats and mice, using immunohistochemistry and in situ hybridization.Results: Following sciatic nerve injury-transection or transection and reanastomosis-ATF3 was strongly upregulated by endoneurial, but not perineurial cells, of the distal stumps of the nerves by 1 day post operation (dpo) and remained strongly expressed in the endoneurium at 30 dpo when axonal regeneration was prevented. Most ATF3+ cells were immunoreactive for the Schwann cell marker, S100. When the nerve was transected and reanastomosed, allowing regeneration of axons, most ATF3 expression had been downregulated by 30 dpo. ATF3 expression was weaker in the proximal stumps of the injured nerves than in the distal stumps and present in fewer cells at all times after injury. ATF3 was upregulated by endoneurial cells in the distal stumps of injured neonatal rat sciatic nerves, but more weakly than in adult animals. ATF3 expression in transected sciatic nerves of mice was similar to that in rats. Following dorsal root injury in adult rats, ATF3 was upregulated in the part of the root between the lesion and the spinal cord (containing Schwann cells), beginning at 1 dpo, but not in the dorsal root entry zone or in the degenerating dorsal column of the spinal cord. Following optic nerve crush in adult rats, ATF3 was found in some cells at the injury site and small numbers of cells within the optic nerve displayed weak immunoreactivity. The pattern of expression of c-Jun in all types of nerve injury was similar to that of ATF3.Conclusion: These findings raise the possibility that ATF3/c-Jun heterodimers may play a role in regulating changes in gene expression necessary for preparing the distal segments of injured peripheral nerves for axonal regeneration. The absence of the ATF3 and c-Jun from CNS glia during Wallerian degeneration may limit their ability to support regeneration

Acute- and late-phase matrix metalloproteinase (MMP)-9 activity is comparable in female and male rats after peripheral nerve injury.

BACKGROUND:In the peripheral nerve, pro-inflammatory matrix metalloproteinase (MMP)-9 performs essential functions in the acute response to injury. Whether MMP-9 activity contributes to late-phase injury or whether MMP-9 expression or activity after nerve injury is sexually dimorphic remains unknown. METHODS:Patterns of MMP-9 expression, activity and excretion were assessed in a model of painful peripheral neuropathy, sciatic nerve chronic constriction injury (CCI), in female and male rats. Real-time Taqman RT-PCR for MMP-9 and its endogenous inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1) of nerve samples over a 2-month time course of CCI was followed by gelatin zymography of crude nerve extracts and purified MMP-9 from the extracts using gelatin Sepharose-beads. MMP excretion was determined using protease activity assay of urine in female and male rats with CCI. RESULTS:The initial upsurge in nerve MMP-9 expression at day 1 post-CCI was superseded more than 100-fold at day 28 post-CCI. The high level of MMP-9 expression in late-phase nerve injury was accompanied by the reduction in TIMP-1 level. The absence of MMP-9 in the normal nerve and the presence of multiple MMP-9 species (the proenzyme, mature enzyme, homodimers, and heterodimers) was observed at day 1 and day 28 post-CCI. The MMP-9 proenzyme and mature enzyme species dominated in the early- and late-phase nerve injury, consistent with the high and low level of TIMP-1 expression, respectively. The elevated nerve MMP-9 levels corresponded to the elevated urinary MMP excretion post-CCI. All of these findings were comparable in female and male rodents. CONCLUSION:The present study offers the first evidence for the excessive, uninhibited proteolytic MMP-9 activity during late-phase painful peripheral neuropathy and suggests that the pattern of MMP-9 expression, activity, and excretion after peripheral nerve injury is universal in both sexes

Gpr126/Adgrg6 has Schwann cell autonomous and nonautonomous functions in peripheral nerve injury and repair

Schwann cells (SCs) are essential for proper peripheral nerve development and repair, although the mechanisms regulating these processes are incompletely understood. We previously showed that the adhesion G protein-coupled receptor Gpr126/Adgrg6 is essential for SC development and myelination. Interestingly, the expression of Gpr126 is maintained in adult SCs, suggestive of a function in the mature nerve. We therefore investigated the role of Gpr126 in nerve repair by studying an inducible SC-specific Gpr126 knock-out mouse model. Here, we show that remyelination is severely delayed after nerve-crush injury. Moreover, we also observe noncell-autonomous defects in macrophage recruitment and axon regeneration in injured nerves following loss of Gpr126 in SCs. This work demonstrates that Gpr126 has critical SC-autonomous and SC-nonautonomous functions in remyelination and peripheral nerve repair. SIGNIFICANCE STATEMENT Lack of robust remyelination represents one of the major barriers to recovery of neurological functions in disease or following injury in many disorders of the nervous system. Here we show that the adhesion class G protein-coupled receptor (GPCR) Gpr126/Adgrg6 is required for remyelination, macrophage recruitment, and axon regeneration following nerve injury. At least 30% of all approved drugs target GPCRs; thus, Gpr126 represents an attractive potential target to stimulate repair in myelin disease or following nerve injury