UNASSIGNED: Herpes zoster (HZ) is a disease caused by the reactivation of the varicella zoster virus. Postherpetic neuralgia (PHN) is the most common complication of HZ.
UNASSIGNED: Repetitive paravertebral block with local anaesthetics and dexmedetomidine for the prevention of PHN in patients with acute herpes zoster.
UNASSIGNED: 104 patients with acute herpes zoster were randomly divided into two groups. Group Rop received repetitive paravertebral block with 0.25% ropivacaine 20 ml per 72 h three times. Group Dex received repetitive paravertebral block with a mixture of 0.25% ropivacaine 20 ml and dexmedetomidine 20 µg per 72 h three times. Patients were permitted to take tramadol when the visual analogue scale (VAS) ≥ 4. The incidence of zoster-related pain was recorded at 1, 3, and 6 months after the end of treatments; VAS scores and the dose of rescue drug were recorded at 1 week, 2 weeks, 1 month, 3 months, and 6 months after the end of treatments.
UNASSIGNED: At 1 month post therapy, the incidence of zoster-related pain was 11% in Group Dex, compared with 35% in Group Rop (p = 0.005). At 3 months post therapy, the incidence of zoster-related pain in Group Dex was still significantly lower than in Group Rop. The VAS scores and the dose of rescue drug in Group Dex were also significantly lower than in Group Rop at each time point (p < 0.05).
UNASSIGNED: Repetitive paravertebral block with local anaesthetics and dexmedetomidine in patients with acute herpes zoster can significantly reduce the incidence of zoster-related pain.

Various techniques have been explored to prolong the duration and improve the efficacy of local anaesthetic nerve blocks. Some of these involve mixing local anaesthetics or adding adjuncts. We did a literature review of studies published between 01 May 2011 and 01 May 2021 that studied specific combinations of local anaesthetics and adjuncts. The rationale behind mixing long- and short-acting local anaesthetics to hasten onset and extend duration is flawed on pharmacokinetic principles. Most local anaesthetic adjuncts are not licensed for use in this manner and the consequences of untested admixtures and adjuncts range from making the solution ineffective to potential harm. Pharmaceutical compatibility needs to be established before administration. The compatibility of drugs from the same class cannot be inferred and each admixture requires individual review. Precipitation on mixing (steroids, non-steroidal anti-inflammatory drugs) and subsequent embolisation can lead to serious adverse events, although these are rare. The additive itself or its preservative can have neurotoxic (adrenaline, midazolam) and/or chondrotoxic properties (non-steroidal anti-inflammatory drugs). The prolongation of block may occur at the expense of motor block quality (ketamine) or block onset (magnesium). Adverse effects for some adjuncts appear to be dose-dependent and recommendations concerning optimal dosing are lacking. An important confounding factor is whether studies used systemic administration of the adjunct as a control to accurately identify an additional benefit of perineural administration. The challenge of how best to prolong block duration while minimising adverse events remains a topic of interest with further research required.

OBJECTIVE: Pain management for the extraction of the mandibular third molar is a challenge as compelling evidence in comparative anaesthetics is currently lacking.
METHODS: Thorough literature searches took place in PubMed, ScienceDirect, CENTRAL, Embase, Web of Science, CBM, and CNKI. Thirty-three trials were meta-analysed using a Bayesian statistical approach within the random-effects model. Grading of Recommendations Assessment, Development, and Evaluation was performed to determine the overall quality of evidence across all comparisons.
RESULTS: In terms of success rate, an inferior alveolar nerve block (IANB) injection of 2% lidocaine with epinephrine was less effective than a combined injection of buccal infiltration (BI) and lingual infiltration (LI) with a 4% articaine (RR = 0.85 [0.75, 0.96], P = 0.611). According to visual analogue scale (VAS), 2% lidocaine-IANB with epinephrine caused higher VAS scores than 4% articaine-IANB with epinephrine (MD = 0.84 [0.28, 1.40], P = 0.057), whereas 0.5% levobupivacaine-IANB showed lower scores than 2% lidocaine-IANB (MD = - 1.62 [- 2.97, - 0.28], P = 0.045). Also, 2% lidocaine-IANB with epinephrine presented longer latency than both 4% articaine-IANB with epinephrine (MD = 39.44 [16.97, 61.90], P < 0.001) and 4% articaine-BI + LI with epinephrine (MD = 164.41 [16.23, 312.58], P < 0.001); 4% articaine-IANB with epinephrine produced shorter latency than 0.5% bupivacaine-IANB with epinephrine (MD = - 42.92 [- 70.28, - 15.56], P = 0.106); 0.75% ropivacaine-IANB caused shorter onset of action compared with 2% lidocaine-IANB (MD = - 40.88 [- 65.50, - 16.26], P < 0.001). In addition, 2% lidocaine-IANB with epinephrine produced significantly shorter duration than both 4% articaine-IANB with epinephrine (MD = - 47.33 [- 57.88, - 36.77], P = 0.265) and 2% mepivacaine-IANB with epinephrine (MD = - 10.01 [- 19.59, - 0.44], P = 0.769). The duration of action triggered by 4% articaine-IANB with epinephrine was shorter compared with 0.5% bupivacaine-IANB with epinephrine (MD = - 64.17 [- 74.65, - 53.69], P = 0.926). Both 0.5% levobupivacaine-IANB and 0.75% ropivacaine-IANB produced longer duration of action than 2% lidocaine-IANB (MD = 333.70 [267.33, 400.07], P < 0.001) and (MD = 288.01 [287.67, 288.34], P = 0.634, respectively).
CONCLUSIONS: The network meta-analysis demonstrated that the intraosseous injection of 4% articaine with epinephrine had the most noteworthy success rate. However, the combination of BI and LI of 4% articaine with epinephrine, and IANB of 0.5% bupivacaine were, according to a VAS, the most effective. It should be noted that a rapid onset of action was produced by BI combined with LI of 4% articaine with epinephrine and IANB of 2% mepivacaine with epinephrine, while the most prolonged duration of action was generated by IANB of 0.5% levobupivacaine or 0.5% bupivacaine.
CONCLUSIONS: For a better understanding of local anaesthesia for the extraction of the third molar, our study was aimed to provide evidence to guide better dental practices in pain management for clinicians.

BACKGROUND: Previous studies suggest that dexmedetomidine has a protective effect against local anaesthetic-induced nerve injury in regional nerve blocks. Whether this potentially protective effect exists in the context of diabetes mellitus is unknown.
METHODS: A diabetic state was established in adult male Sprague-Dawley rats with intraperitoneal injection of streptozotocin. Injections of ropivacaine 0.5%, dexmedetomidine 20 μg kg-1 (alone and in combination), or normal saline (all in 0.2 ml) were made around the sciatic nerve in control and diabetic rats (n=8 per group). The duration of sensory and motor nerve block and the motor nerve conduction velocity (MNCV) were determined. Sciatic nerves were harvested at post-injection day 7 and assessed with light and electron microscopy or used for pro-inflammatory cytokine measurements.
RESULTS: Ropivacaine and dexmedetomidine alone or in combination did not produce nerve fibre damage in control non-diabetic rats. In diabetic rats, ropivacaine induced significant nerve fibre damage, which was enhanced by dexmedetomidine. This manifested with slowed MNCV, decreased axon density, and decreased ratio of inner to outer diameter of the myelin sheath (G ratio). Demyelination, axon disappearance, and empty vacuoles were also found using electron microscopy. An associated increase in nerve interleukin-1β and tumour necrosis factor-α was also seen.
CONCLUSIONS: Ropivacaine 0.5% causes significant sciatic nerve injury in diabetic rats that is greatly potentiated by high-dose dexmedetomidine. Although the dose of dexmedetomidine used in this study is considerably higher than that used in clinical practice, our data suggest that further studies to assess ropivacaine (alone and in combination with dexmedetomidine) use for peripheral nerve blockade in diabetic patients are warranted.

BACKGROUND: Neurotoxicity induced by the local anaesthetics has aroused concern. A previous study has shown that an overload of intracellular calcium was involved in the neurotoxic effect. Cav3.1 is one of the low-voltage-activated (LVA) calcium channels which play a key point to regulate the intracellular calcium ion level. This study aimed to investigate the changes of the Cav3.1 expression in the SH-SY5Y cells treated with lidocaine hydrochloride.
METHODS: The SH-SY5Y cells were treated with different concentrations of lidocaine hydrochloride(1 mM, 5 mM and 10 mM, namely L1 group, L5 group and L10 group) and different exposure times (1 h,12 h and 24 h), respectively. Cell viability, Cav3.1 protein and mRNA expression were detected.
RESULTS: The results showed that cell viability decreased and Cav3.1 mRNA and protein expression increased with the concentration (from 1 mM to 10 mM) of the lidocaine hydrochloride and exposure time (from 1 h to 24 h) to the SH-SY5Y cell line increased.
CONCLUSIONS: Those data showed that lidocaine hydrochloride induced SH-SY5Y cell toxicity and up-regulated Cav3.1mRNA and protein expression.

Neurotoxicity of local anaesthetics has been alerted by more and more peoples. Cav3.1 and Cav3.2 T-type calcium channels were closely related with local anaesthetics toxicity. However, the role of Cav3.3, another subtype of the T-type calcium channel, on the neurotoxicity induced by local anaesthetics remains unclear. CaMKIIγ is a kind of multifunctional kinase and associated with a variety of physiological and pathological process. T-type calcium channel is closely related with CaMKIIγ. Up-regulation CaMKIIγ can increase T-type currents at the dorsal root ganglia (DRG). On the contrary, down-regulation results in the T-type currents decrease. Is the relation between Cav3.3 T-type channel calcium and CaMKIIγ involved with the ropivacaine hydrochloride neurotoxicity? In this study, we generated pAd-Cav3.3 and pAd-shRNA adenovirus vector to up-regulate and down-regulate Cav3.3 mRNA expression of the DRG. The cells treated or untreated with ropivacaine hydrochloride (3 mM) for 4 h were used to evaluate the neurotoxicity. Cell viability, cell death rate and apoptosis rate, Cav3.3 and CaMKIIγ expression were detected with MTT method, Hoechst-PI, flow cytometry, qRT-PCR and western blotting. Results showed that the cell viability of the DRG treated with ropivacaine hydrochloride markedly decreased, death rate and apoptosis rate, Cav3.3 and CaMKIIγ mRNA and protein expression significantly increased. Cav3.3 overexpression aggravated DRG injury induced by ropivacaine hydrochloride and inhibition of Cav3.3 expression improved the cell damages. Cav3.3 can regulate CaMKIIγ mRNA and protein expression. In conclusion, Cav3.3 regulated CaMKIIγ in DRG, which was involved with the cell injury induced by ropivacaine hydrochloride.

The local anaesthetics (LAs) are widely used for peripheral nerve blocks, epidural anaesthesia, spinal anaesthesia and pain management. However, exposure to LAs for long duration or at high dosage can provoke potential neuronal damages. Autophagy is an intracellular bulk degradation process for proteins and organelles. However, both the effects of LAs on autophagy in neuronal cells and the effects of autophagy on LAs neurotoxicity are not clear. To answer these questions, both lipid LAs (procaine and tetracaine) and amide LAs (bupivacaine, lidocaine and ropivacaine) were administrated to human neuroblastoma SH-SY5Y cells. Neurotoxicity was evaluated by MTT assay, morphological alterations and median death dosage. Autophagic flux was estimated by autolysosome formation (dual fluorescence LC3 assay), LC3-II generation and p62 protein degradation (immunoblotting). Signalling alterations were examined by immunoblotting analysis. Inhibition of autophagy was achieved by transfection with beclin-1 siRNA. We observed that LAs decreased cell viability in a dose-dependent manner. The neurotoxicity of LAs was tetracaine > bupivacaine > ropivacaine > procaine > lidocaine. LAs increased autophagic flux, as reflected by increases in autolysosome formation and LC3-II generation, and decrease in p62 levels. Moreover, LAs inhibited tuberin/mTOR/p70S6K signalling, a negative regulator of autophagy activation. Most importantly, autophagy inhibition by beclin-1 knockdown exacerbated the LAs-provoked cell damage. Our data suggest that autophagic flux was up-regulated by LAs through inhibition of tuberin/mTOR/p70S6K signalling, and autophagy activation served as a protective mechanism against LAs neurotoxicity. Therefore, autophagy manipulation could be an alternative therapeutic intervention to prevent LAs-induced neuronal damage.

A highly selective and sensitive method of reversed phase high-performance liquid chromatography (RP-HPLC) coupled with resonance Rayleigh scattering (RRS) was developed for the determination of procaine, bupivacaine and tetracaine. Separation of three local anaesthetics was achieved at 35 °C on a C18 column. The mobile phase was 30: 70 (v/v) acetonitrile/triethylamine-phosphoric acid buffer (pH 2.9) at flow rate of 0.3 mL/min. The RRS detection was conducted by taking advantage of the strong RRS enhancement of the local anaesthetics with erythrosine reaction in an acidic medium. Under optimum conditions, the limit of detection (S/N = 3) values were in the range of 2.4-11.2 ng/mL. Recoveries from spiked human urine samples were 95.8%-104.5%. The proposed method applied to the determination of local anaesthetics in human urine achieved satisfactory results. In addition, the mechanism of the reaction is fully discussed. Copyright © 2016 John Wiley & Sons, Ltd.