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

The properties of nerve cell precursors in hydra

Two signals, the head activator and an injury stimulus, control differentiation of nerve cells from uncommitted stem cells in hydra [Th. Holstein, H. C. Schaller, and C. N. David, (1986) Dev. Biol. 115, 9–17]. The time of action of these signals in the precursor cell cycle was determined. Methanol extracts of hydra containing 10−13 M head activator cause nerve cell commitment in S phase of the precursor cell cycle. Committed precursors complete the cell cycle, divide, and arrest in G1. Injury relieves the G1 block and precursors differentiate nerve cells. Under these conditions the time from commitment to nerve differentiation is 12 hr, the time from the end of S phase to nerve differentiation is 9 hr, and the time from the G1 block to nerve differentiation is 4 hr. Committed precursors blocked in G1 are unstable, decaying with a half-life of 12 hr if not stimulated to differentiate by an injury stimulus

Ultrasound-Guided Lateral Femoral Cutaneous Nerve Cryoneurolysis for Analgesia in Patients With Burns.

Autologous skin grafting from the thigh is frequently required for treatment of burns and is associated with intense pain at the donor site. Local anesthetic-based (LA) nerve blocks of the lateral femoral cutaneous nerve (LFCN) have been demonstrated to provide analgesia when the graft is taken from the lateral thigh. However, the duration of these single injection blocks has been reported to average only 9 hours, whereas the pain from the procedure lasts days or weeks. Continuous LA nerve blocks can also be used to provide analgesia during serial debridement of burns, although this requires placement of a perineural catheter which may increase infection risk in a population with an increased susceptibility to infection. Cryoneurolysis of the LFCN can potentially provide analgesia of the lateral thigh for skin graft harvesting or serial burn debridement that lasts far longer than conventional LA nerve blocks. Here, we present a series of three patients who received a combination of a LA nerve block and cryoneurolysis nerve block of the LFCN for analgesia of the lateral thigh. Two of these patients had the blocks placed before harvesting a split thickness skin graft. The third received the blocks for outpatient wound care of a burn to the lateral thigh. In all cases, the resulting analgesia lasted more than 1 week. A single cryoneurolysis block of the LFCN successfully provided extended duration analgesia of the lateral thigh for autologous skin graft donor site or wound care of a burn in three patients

Nerve localization techniques for peripheral nerve block and possible future directions

Ultrasound guidance is now a standard nerve localization technique for peripheral nerve block (PNB). Ultrasonography allows simultaneous visualization of the target nerve, needle, local anesthetic injectate and surrounding anatomical structures. Accurate deposition of local anesthetic next to the nerve is essential to the success of the nerve block procedure. Unfortunately, due to limitations in the visibility of both needle tip and nerve surface, the precise relationship between needle tip and target nerve is unknown at the moment of injection. Importantly, nerve injury may result both from an inappropriately placed needle tip and inappropriately placed local anesthetic. The relationship between the block needle tip and target nerve is of paramount importance to the safe conduct of peripheral nerve block. This review summarizes the evolution of nerve localization in regional anesthesia, characterizes a problem faced by clinicians in performing ultrasound guided nerve block and explores the potential technological solutions to this problem

Effects of early and late diabetic neuropathy on sciatic nerve block duration and neurotoxicity in Zucker diabetic fatty rats

Background The neuropathy of type II diabetes mellitus (DM) is increasing in prevalence worldwide. We aimed to test the hypothesis that in a rodent model of type II DM, neuropathy would lead to increased neurotoxicity and block duration after lidocaine-induced sciatic nerve block when compared with control animals. Methods Experiments were carried out in Zucker diabetic fatty rats aged 10 weeks (early diabetic) or 18 weeks (late diabetic, with or without insulin 3 units per day), and age-matched healthy controls. Left sciatic nerve block was performed using 0.2 ml lidocaine 2%. Nerve conduction velocity (NCV) and F-wave latency were used to quantify nerve function before, and 1 week after nerve block, after which sciatic nerves were used for neurohistopathology. Results Early diabetic animals did not show increased signs of nerve dysfunction after nerve block. In late diabetic animals without insulin vs control animals, NCV was 34.8 (5.0) vs 41.1 (4.1) ms s−1 (P<0.01), and F-wave latency was 7.7 (0.5) vs 7.0 (0.2) ms (P<0.01), respectively. Motor nerve block duration was prolonged in late diabetic animals, but neurotoxicity was not. Late diabetic animals receiving insulin showed intermediate results. Conclusions In a rodent type II DM model, nerves have increased sensitivity for short-acting local anaesthetics without adjuvants in vivo, as evidenced by prolonged block duration. This sensitivity appears to increase with the progression of neuropathy. Our results do not support the hypothesis that neuropathy due to type II DM increases the risk of nerve injury after nerve bloc

Focal conduction block in the dorsal root ganglion in experimental allergic neuritis

Acute experimental allergic neuritis was induced in Lewis rats by inoculation with bovine intradural root myelin and adjuvants. In terminal experiments, sensory conduction was assessed in rats with hindlimb ataxia and weakness by stimulating the exposed sciatic nerve and recording directly from the exposed L-4 spinal nerve, dorsal root ganglion, dorsal root, and dorsal root entry zone. Focal conduction block was present in a high proportion of large-diameter fibers in the dorsal root ganglion. In contrast, nerve conduction in the peripheral nerve and spinal nerve was essentially normal apart from probable conduction block in some fibers in the proximal spinal nerve in a minority of rats. The afferent volley arriving at the dorsal root entry zone of the spinal cord was greatly reduced, as a consequence of the conduction block in the dorsal root ganglion and probable conduction block in the dorsal root. The M wave recorded from the fourth dorsal interosseus muscle of the hindfoot was normal in amplitude but slightly prolonged in latency and the H reflex was absent. These electrophysiological findings correlated well with the histological findings of inflammation and prominent demyelination in the dorsal root ganglia and dorsal roots with minimal involvement of the proximal spinal nerve and no involvement of the sciatic nerve. It is concluded that the hindlimb ataxia in rats with this form of acute experimental allergic neuritis is due to demyelination-induced nerve conduction block in the dorsal root ganglia and probably in the dorsal roots

Description of a new approach for great auricular and auriculotemporal nerve blocks: A cadaveric study in foxes and dogs

Otitis externa is a painful condition that may require surgical intervention in dogs. A balanced analgesia protocol should combine systemic analgesic agents and local anaesthesia techniques. The aim of the study was to find anatomical landmarks for the great auricular and the auriculotemporal nerves that transmit nociceptive information from the ear pinna and to develop the optimal technique for a nerve block. The study consisted of two phases. In phase I, one fox cadaver was used for dissection and anatomical localization of the auricular nerves to derive landmarks for needle insertion. Eight fox cadavers were subsequently used to evaluate the accuracy of the technique by injecting methylene blue bilaterally. In phase II findings from phase I were applied in four Beagle canine cadavers. A block was deemed successful if more than 0.6 cm of the nerve's length was stained. Successful great auricular nerve block was achieved by inserting the needle superficially along the wing of the atlas with the needle pointing towards the jugular groove. For the auriculotemporal nerve block the needle was inserted perpendicular to the skin at the caudal lateral border of the zygomatic arch, close to the temporal process. The overall success rate was 24 out of 24 (100%) and 22 out of 24 (91%) for the great auricular and the auriculotemporal nerves, respectively, while the facial nerve was stained on three occasions. Our results suggest that it is feasible to achieve a block of the auricular nerves, based on anatomical landmarks, without concurrently affecting the facial nerv

The Effects of 0.3 mA and 0.5 mA Threshold Currents on Axillary Brachial Plexus Block

Aim:The nerve block success by peripheral nerve stimulator may be increased by optimal nerve localization. However, it is not clear which current threshold is more suitable for this. Material and Methods: Forty patients between 18-60 years of age were included in this randomized, double blind study. In group 1 (n=20) and group 2 (n=20), the thresholds of current were 0.3 mA and 0.5 mA respectively. The mixture of 150 mg of levobupivacaine (0.5%) and 200 mg of lidocaine (2%) in a total volume of 40 ml was injected around the radial nerve. The duration of postoperative sensory and motor block and the first analgesic requirement were measured. Results; The onset of sensory and motor block of the musculocutaneus (p=0.01 and p=0.004 respectively) and the onset of motor block of the median and ulnar nerve (p=0.009 and p=0.02 respectively) were significantly shorter in group 1 than in group 2. The duration of postoperative sensory and motor block and the time to first analgesic requirement were significantly longer in group 1 than in group 2 (p=0.0001). Conclusions; The 0.3 mA current is more beneficial than 0.5 mA current in shortening the onset of sensory and motor block, lengthening the postoperative sensory and motor block and the duration of first analgesic requirement

Gene therapy targeting SARM1 blocks pathological axon degeneration in mice

Axonal degeneration (AxD) following nerve injury, chemotherapy, and in several neurological disorders is an active process driven by SARM1, an injury-activated NADase. Axons of SARM1-null mice exhibit greatly delayed AxD after transection and in models of neurological disease, suggesting that inhibiting SARM1 is a promising strategy to reduce pathological AxD. Unfortunately, no drugs exist to target SARM1. We, therefore, developed SARM1 dominant-negatives that potently block AxD in cellular models of axotomy and neuropathy. To assess efficacy in vivo, we used adeno-associated virus-mediated expression of the most potent SARM1 dominant-negative and nerve transection as a model of severe AxD. While axons of vehicle-treated mice degenerate rapidly, axons of mice expressing SARM1 dominant-negative can remain intact for \u3e10 d after transection, similar to the protection observed in SARM1-null mice. We thus developed a novel in vivo gene therapeutic to block pathological axon degeneration by inhibiting SARM1, an approach that may be applied clinically to treat manifold neurodegenerative diseases characterized by axon loss

PolyMorphine provides extended analgesic-like effects in mice with spared nerve injury.

AbstractMorphine is a well-characterized and effective analgesic commonly used to provide pain relief to patients suffering from both acute and chronic pain conditions. Despite its widespread use and effectiveness, one of the major drawbacks of morphine is its relatively short half-life of approximately 4 h. This short half-life often necessitates multiple administrations of the drug each day, which may contribute to both dependence and tolerance to morphine. Here, we tested the analgesic properties of a new polymer form of morphine known as PolyMorphine. This polymer has monomeric units of morphine incorporated into a poly(anhydride-ester) backbone that has been shown to hydrolyze into free morphine in vitro. Using an animal model of chronic pain, the spared nerve injury surgery, we showed that PolyMorphine is able to block spared nerve injury-induced hypersensitivity in mice for up to 24-h post-administration. Free morphine was shown to only block spared nerve injury-induced hypersensitivity for up to 2-h post-injection. PolyMorphine was also shown to act through the mu opioid receptor due to the ability of naloxone (a mu opioid receptor antagonist) to block PolyMorphine-induced analgesia in spared nerve injury animals pretreated with PolyMorphine. Additionally, we observed that PolyMorphine causes similar locomotor and constipation side effects as free morphine. Finally, we investigated if PolyMorphine had any effects in a non-evoked pain assay, conditioned place preference. Pretreatment of spared nerve injury mice with PolyMorphine blocked the development of conditioned place preference for 2-methyl-6-(phenylethynyl)pyridine (MPEP), a short-lasting mGluR5 antagonist with analgesic-like properties. Free morphine does not block the development of preference for MPEP, suggesting that PolyMorphine has longer lasting analgesic effects compared to free morphine. Together, these data show that PolyMorphine has the potential to provide analgesia for significantly longer than free morphine while likely working through the same receptor