Peripheral neuropathic pain is a disabling condition resulting from nerve injury. It is characterized by the dysregulation of voltage-gated sodium channels (Na v s) expressed in dorsal root ganglion (DRG) sensory neurons. The mechanisms underlying the altered expression of Na v s remain unknown. This study investigated the role of the E3 ubiquitin ligase NEDD4-2, which is known to ubiquitylate Na v s, in the pathogenesis of neuropathic pain in mice. The spared nerve injury (SNI) model of traumatic nerve injury-induced neuropathic pain was used, and an Na v 1.7-specific inhibitor, ProTxII, allowed the isolation of Na v 1.7-mediated currents. SNI decreased NEDD4-2 expression in DRG cells and increased the amplitude of Na v 1.7 and Na v 1.8 currents. The redistribution of Na v 1.7 channels toward peripheral axons was also observed. Similar changes were observed in the nociceptive DRG neurons of Nedd4L knockout mice (SNS-Nedd4L -/-). SNS-Nedd4L -/-mice exhibited thermal hypersensitivity and an enhanced second pain phase after formalin injection. Restoration of NEDD4-2 expression in DRG neurons using recombinant adenoassociated virus (rAAV2/6) not only reduced Na v 1.7 and Na v 1.8 current amplitudes, but also alleviated SNI-induced mechanical allodynia. These findings demonstrate that NEDD4-2 is a potent posttranslational regulator of Na v s and that downregulation of NEDD4-2 leads to the hyperexcitability of DRG neurons and contributes to the genesis of pathological pain.

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Objective Multimodal pain management strategies aim to improve postoperative pain control. The purpose of this study was to analyze pain scores and risk factors for acute postoperative pain after various abdominal surgery procedures. Methods Data on 11 different abdominal surgery procedures were prospectively recorded. Pain intensity (rest, mobilization) and patient satisfaction at discharge were assessed using a visual analog scale (VAS; 0–10), and analgesic consumption was recorded until 96 hours postoperation. Demographic, surgery-related, and pain management–related univariate risk factors for insufficient pain control (VAS ≥ 4) were entered in a multivariate logistic regression model. Results A total of 1,278 patients were included. Overall, mean VAS scores were <3 at all time points, and scores at mobilization were consistently higher than at rest (P < 0.05). Thirty percent of patients presented a prolonged VAS score ≥4 at mobilization at 24 hours, significantly higher than at rest (14%, P < 0.05). High pain scores correlated with high opioid consumption, whereas a variability of pain scores was observed in patients with low opioid consumption. The only independent risk factor for moderate and severe pain (VAS ≥ 4) was younger age (<70 years, P = 0.001). The mean satisfaction score was 8.18 ± 1.29. Conclusions Among 1,278 patients, pain was controlled adequately during the first four postoperative days, resulting in high levels of patient satisfaction. Pain levels were higher at mobilization. Younger age was the only independent risk factor for insufficient pain control. Preventive treatment in patients <70 years old and before mobilization could be evaluated for potential improvement.

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BackgroundImmediate laparoscopic cholecystectomy is the accepted standard for the treatment of acute cholecystitis. The aim of the present study was to evaluate the feasibility of a standardized approach with tailored care maps for pre- and postoperative care by comparing pain, nausea and patient satisfaction after elective and emergent laparoscopic cholecystectomy.MethodsFrom January 2014 until April 2015, data on pain and nausea management were prospectively recorded for all elective and emergency procedures in the department of visceral surgery. This prospective observational study compared consecutive laparoscopic elective vs. emergency cholecystectomies. Visual analogue scales (VAS) were used to measure pain, nausea, and satisfaction from recovery room until 96 hours postoperatively.ResultsFinal analysis included 168 (79%) elective cholecystectomies and 44 (21%) emergent procedures. Demographics (Age, gender, BMI and ASA-scores) were comparable between the 2 groups. In the emergency group, patients did not receive anxiolytic medication (0% vs.13%, p = 0.009) and less postoperative nausea and vomiting (PONV) prophylaxis (77% vs. 97% p = <0.001). Perioperative pain management was similar in terms of opioid consumption (median amount of fentanyl 450ug [IQR 350-500] vs. 450ug [375-550], p = 0.456) and wound infiltration rates (24% vs. 25%, p = 0.799). Postoperative consumption of paracetamol, metamizole and opiod medications were similar between the 2 groups. VAS scores for pain (p = 0.191) and nausea (p = 0.392) were low for both groups. Patient satisfaction was equally high in both clinical settings (VAS 8.5 ± 1.1 vs. 8.6 ± 1.1, p = 0.68).ConclusionsA standardized pathway allows equally successful control of pain and nausea after both elective and emergency laparoscopic cholecystectomy.This study was retrospectively registered by March 01, 2016 in the following trial register: www.researchregistry.com (UIN researchregistry993)Electronic supplementary materialThe online version of this article (doi:10.1186/s12893-016-0194-6) contains supplementary material, which is available to authorized users.

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