An integrated analysis of herpes virus infections from eight randomized clinical studies of baricitinib in adults with moderate-to-severe atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is associated with an increased risk for viral infections including those caused by herpes simplex virus and varicella zoster virus. OBJECTIVES: This study examined treatment-emergent (TE) herpes simplex infection including eczema herpeticum (EH), and herpes zoster (HZ), in adult patients with AD receiving ≥1 dose of baricitinib (BARI), an oral selective inhibitor of Janus kinase 1/2. METHODS: We evaluated data from six double-blinded, randomized, placebo-controlled (PC) trials and two long-term extension studies, within three analysis sets: PC, 2-4-mg BARI extended and All-BARI-AD. Frequency, incidence rate (IR)/100 person-years (PYs) and clinical characteristics of TE-herpes simplex, EH and HZ were reported. RESULTS: In the All-BARI-AD dataset (n = 2531; 2247 PYs), herpes simplex was reported in 8.9% of patients (n = 224; IR = 10.3). Most herpes simplex events were rated as mild or moderate (93.3%), rarely led to permanent discontinuation (2.2%) and presented mostly as oral/perioral herpes simplex (51.3%). TE-EH occurred at a low frequency (All-BARI-AD 1.7% n = 43; IR = 2.0) and were reported in 0.5%, 0.2% and 1.4% of patients receiving placebo, 2-mg or 4-mg BARI respectively. In the All-BARI-AD dataset, most events were investigator-rated as mild/moderate (79.1%), affected ≤2% of the body surface area (74.2%) and occurred as single events (88.4%). Serious TE-EH (n = 11) occurred exclusively in patients with poor disease control (vIGA-AD™ score ≥3) at infection onset. TE-HZ was reported in 2.1% of BARI patients (n = 53; IR = 2.3), without a dose relationship during the PC period (IR = 2.7 and IR = 0.0) or the extended dataset (IR = 3.7 and IR = 1.7) for 2- or 4-mg BARI respectively. CONCLUSIONS: TE-herpes simplex was common, while occurrence of EH was uncommon. Most events of EH were localized with involvement of a small BSA and were linked to poor disease control. Events of HZ were rare in the PC dataset and without a dose dependent increase in frequency.

A closer look at 30 day hospital readmissions after head and neck cancer surgery.

PURPOSE: 30-day hospital readmissions after head and neck cancer surgery continue to be a significant source of patient harm and healthcare expenditure. While there is substantial data in the literature assessing predictive factors for readmissions after head and neck cancer surgery, there are a paucity of studies which attempt to understand if such readmissions are preventable. The goal of this paper is to determine factors associated with 30-day hospital readmissions after head and neck cancer surgery and to understand if these readmissions were preventable. MATERIALS AND METHODS: Retrospective review from a single academic tertiary care center. Patients readmitted within 30 days after undergoing surgery for cancers of the head and neck between 2015 and 2018 were identified. RESULTS: Over a 3-year period, 26 patients undergoing resection with or without reconstruction of head and neck cancers were readmitted to the hospital within 30 days of discharge. There were 15 (58%) men and 11 (42%) women with a mean age of 68 years (SD 14 years). Twenty-one (81%) patients had squamous cell carcinoma and 13 (50%) had a primary site in the oral cavity. Thirteen (50%) had undergone free or regional flap reconstruction. The indication for readmission was related to the surgical wound in 19 (73%) and to medical complications in 7 (27%). Each case was categorized as "possibly preventable" versus "uncertain if preventable" based on whether a reasonable and feasible change in management may have prevented readmission. Six (23%) readmissions were deemed possibly preventable. Four were related to the surgical wound where initial free or regional flaps may have prevented complication. Two were medical complications that may have benefited from longer inpatient observation. CONCLUSIONS: For a subset of patients readmitted within 30 days of head and neck cancer surgery, a reasonable and feasible change in management may have prevented their hospital readmission. The significance of better understanding this patient population is underscored by the high mortality rate.

[Pain therapy in in-patients with cancer. Effects of a manual-based approach as guideline for pain-consulting service at a university hospital]. / Stationäre medikamentöse Schmerztherapie bei Tumorpatienten: Effekte einer manualisierten Leitlinie für den Konsildienst eines Universitätsklinikums.

BACKGROUND: Appropriate medication is an important and substantial part in the therapy of tumor-induced pain. OBJECTIVE: The objective of this study was to investigate the efficiency of anaesthesiology-based consultant service characterizing the quality of this type of treatment in daily clinical practice of a university hospital, i. e., in the patient profile of a tertiary center (study design: systematic clinical, unicenter observational study reflecting clinical practice and study-based control of therapeutic care quality). METHODS: In the course of consulting function with regard to pain care on the single wards a considerable portion of cancer patients are recieving drugs. For most patients such care comprises several consultations and subsequently initiated treatment modifications. The consulting function ends if the patients feel free of pain or report a substantial improvement. From 1/1/2010 to 12/31/2012 detailed information on the drug therapy applied prior to, during and after the consultation was prospectively documented.This data was retrospectively evaluated as "pre-vs.-post" comparison (Chi-squared test, Fisher's exact test and McNemar's test), in particular, focussing on the quality of pain medication using the WHO index as well as pain intensity obtained by means of the visual analogue scale (VAS). RESULTS: In total, 375 in-patients were treated. The modified pain medication by the anesthesiological consultant service led to a significant increase (p < 0.001; Wilcoxon's test) in the mean WHO index from 6.37 (SD, 1.83) to 8.43 (SD, 1.47). Furthermore, a reduction of VAS from 5.00 (SD, 2.39) to 2.64 (SD, 1.64) was noted (p < 0.001; Wilcoxon's test). CONCLUSION: The consequent application of established guidelines (according to WHO scheme) and the WHO index leads to a qualitative and measurable improvement of drug therapy for cancer-related pain.

Washout of sevoflurane from the GE Avance and Amingo Carestation anesthetic machines.

BACKGROUND: Inhalational anesthetics must be removed from anesthetic machines to prevent malignant hyperthermia (MH) in susceptible patients or to treat MH occurring during inhalational general anesthesia. This study examines the sevoflurane washout from the GE Avance and Amingo Carestations™. METHODS: The care stations were contaminated with sevoflurane during general anesthesia. Then, the vaporizer was removed, the CO2 absorber was exchanged against an empty one and the breathing tubes were substituted by clean ones. In the first part, the fresh gas flow was 10 l/min. In the second part, the Advanced Breathing System™ (ABS™), the internal breathing circuit, was replaced by a laundered component. The fresh gas flow was set to 10 l/min for 10 min and to 5 l/min for the following 20 min. RESULTS: In the 25 measurements of the first part, the sevoflurane concentration decreased from a median of 31.60 ppm [interquartile range (IQR) 130.12 ppm] within 22 min in every case to values below 5 ppm and stayed there for the last 8 min of the measuring (P < 0.0001). In the 15 measurements of the second part, the sevoflurane concentration fell from the median of 8.56 ppm (IQR 8.99 ppm) within 5 min to values being significantly below 5 ppm and stayed there for the following 25 min (P < 0.0001). CONCLUSIONS: In case of sudden onset of MH, the Avance or Amingo Carestation™ can stay in place, if the fresh gas flow is increased to 10 l/min or more. To prepare these machines for MH-susceptible patients, the ABS™ should be substituted by a laundered component.

Involvement of multiple loci in quorum quenching of autoinducer I molecules in the nitrogen-fixing symbiont Rhizobium (Sinorhizobium) sp. strain NGR234.

Rhizobium sp. strain NGR234 is a unique alphaproteobacterium (order Rhizobiales) that forms nitrogen-fixing nodules with more legumes than any other microsymbiont. Since we have previously described the complete genome sequence of NGR234, we now report on a genome-wide functional analysis of the genes and enzymes involved in autoinducer I hydrolysis in this microbe. Altogether we identified five cosmid clones that repeatedly gave a positive result in our function-based approach for the detection of autoinducer I hydrolase genes. Of these five cosmid clones, two were located on pNGR234b and three were on cNGR234. Subcloning and in vitro mutagenesis in combination with BLAST analyses identified the corresponding open reading frames (ORFs) of all cosmid clones: dlhR, qsdR1, qsdR2, aldR, and hitR-hydR. Analyses of recombinant DlhR and QsdR1 proteins by using high-performance liquid chromatography-mass spectrometry (HPLC-MS) demonstrate that these enzymes function as acyl homoserine lactone (AHL) lactonases. Furthermore, we showed that these enzymes inhibited biofilm formation and other quorum-sensing-dependent processes in Pseudomonas aeruginosa, Chromobacterium violaceum, and Agrobacterium tumefaciens. Finally, our experimental data suggest that competitive colonization of roots in the rhizospheres of cowpea plants is affected by DlhR and QsdR1.

BpiB05, a novel metagenome-derived hydrolase acting on N-acylhomoserine lactones.

The N-acyl-homoserine lactones (N-AHLs) play an important role in bacterial cell-cell signaling. Up to date, however, only a few different experimentally proven classes of N-AHL ring-cleaving enzymes are known. Here we report on the isolation and biochemical characterization of a novel hydrolase derived from the soil metagenome and acting on N-AHLs. The identified protein designated BpiB05 is weakly similar to hypothetical proteins from Bacteroides fragilis, the draft genomes of two Burkholderia species as well as a marine metagenomic ORF but is otherwise not similar to any known protein. BpiB05 was overexpressed in Escherichia coli as a 10× His-tagged fusion protein. The recombinant protein revealed a molecular weight of about 70kDa and was tested for its quorum quenching (QQ) activities using a lacZ-bioassay. Additional HPLC-MS analyses confirmed the lactonolytic activity of the purified protein in the presence of Ca²âº. Further tests suggested that BpiB05 strongly reduces motility in Pseudomonas aeruginosa, pyocyanin synthesis and biofilm formation in this microbe. Because BpiB05 is not distantly related to any of the currently known hydrolases it forms probably a novel group within the growing number of proteins acting on N-AHLs.

Metagenome-derived clones encoding two novel lactonase family proteins involved in biofilm inhibition in Pseudomonas aeruginosa.

Here we report the isolation and characterization of three metagenome-derived clones that interfere with bacterial quorum sensing and degrade N-(3-oxooctanoyl)-l-homoserine lactone (3-oxo-C(8)-HSL). By using a traI-lacZ gene fusion, the metagenome-derived clones were identified from a soil DNA library and analyzed. The open reading frames linked to the 3-oxo-C(8)-HSL-degrading activities were designated bpiB01, bpiB04, and bpiB07. While the BpiB07 protein was similar to a known lactonase, no significant similarities were observed for the BpiB01 and BpiB04 proteins or the deduced amino acid sequences. High-performance liquid chromatography-mass spectrometry analyses confirmed that the identified genes encode novel lactone-hydrolyzing enzymes. The original metagenome-derived clones were expressed in Pseudomonas aeruginosa and employed in motility and biofilm assays. All clones were able to reproducibly inhibit motility in P. aeruginosa. Furthermore, these genes clearly inhibited biofilm formation in P. aeruginosa when expressed in P. aeruginosa PAO1. Thus, this is the first study in which metagenome-derived proteins have been expressed in P. aeruginosa to successfully inhibit biofilm formation.

[Postoperative pain management. Application of an iontophoretic patient-activated transdermal system]. / Postoperative Schmerztherapie. Einsatz des iontophoretischen, patientenaktivierten transdermalen Systems.

Intravenous patient-controlled analgesia (i.v. PCA) for parenteral postoperative pain control is considered standard therapy as patients can individually titrate the amount of analgesic as needed. Iontophoretic patient-activated transdermal systems (IPATS) are a new non-invasive pre-programmed method for postoperative pain control. By pressing the dosing button a 40 microg dose of fentanyl is delivered over a 10 min period via iontophoresis through the intact skin. Several comparative randomized controlled trials have demonstrated that IPATS provide postoperative pain control equivalent to i.v. PCA with morphine. Thus, IPATS is a new method in the management of acute postoperative pain which increases patient mobility and reduces time and effort of care as well as the risk of programming errors. In this review the efficacy, pharmacokinetics, handling and process cost-effectiveness of IPATS are discussed.

[Study protocol of the VISEP study. Response of the SepNet study group]. / Studienprotokoll der VISEP-Studie. Entgegnung der SepNet-Studiengruppe.

In the commentary by Zander et al. the authors appear concerned about the methods and results of our, at that time, unpublished sepsis trial evaluating hydroxyethyl starch (HES) and insulin therapy. Unfortunately, the authors' concerns are based on false assumptions about the design, conduct and modes of action of the compounds under investigation. For instance, in our study the HES solution was not used for maintenance of daily fluid requirements, so that the assumption of the authors that this colloid was used "exclusively" is wrong. Moreover, the manufacturer of Hemohes, the HES product we used, gives no cut-off value for creatinine, thus the assumption that this cut-off value was "doubled" in our study is also incorrect. Other claims by the authors such as that lactated solutions cause elevated lactate levels, iatrogenic hyperglycemia and increase O(2) consumption are unfounded. There is no randomized controlled trial supporting such a claim - this claim is neither consistent with our study data nor with any credible published sepsis guidelines or with routine practice worldwide. We fully support open scientific debate. Our study methods and results have now been published after a strict peer-reviewing process and this data is now open to critical and constructive reviewing. However, in our opinion this premature action based on wrong assumptions and containing comments by representatives of pharmaceutical companies does not contribute to a serious, unbiased scientific discourse.

[Practicability of a German version of the "Oswestry Low Back Pain Disability Questionnaire". A questionnaire to assess disability caused by back pain]. / Praxistauglichkeit einer deutschen Version des "Oswestry Low Back Pain Disability Questionnaire". Ein Fragebogen zur Beeinträchtigung durch Rückenschmerzen.

While caring for patients with chronic low back pain, a standardized measurement of pain and pain-related reduction of the quality of life is needed. Easy application and data collection are decisive for routine use. The Oswestry Low Back Pain Disability Questionnaire is an internationally widely used instrument, which was now scrutinized in 148 patients in two orthopedic hospitals. A higher pain disability was related to age, female gender, limitations experienced in social life, impact of pain, use of analgetics, low net income, and patients in Eastern Germany. The available German version of the questionnaire is suitable for daily use to measure the intensity of pain and pain-related disability in everyday life, including social impairment due to low back pain.

[A survey of labour pain management in Germany]. / Eine Umfrage zur geburtshilflichen Schmerztherapie in Deutschland.

BACKGROUND: In a survey of German hospitals with obstetric units, data on anaesthesia and analgesia in obstetric pain management were collected. METHODS: At each of 918 hospitals with obstetric units, the head of the anaesthetic department received a questionnaire on obstetric pain management. RESULTS: The response rate was 47.1%. On average, there were 748+/-407 (median 663;1st/3rd quartiles 309/1,303) births per year and hospital, 69.4% with spontaneous vaginal delivery. Opioids were the systemic analgesics most frequently administered in the delivery rooms. Epidural analgesia (EA) was given to 17.5+/-12.6% of the parturients. The number of deliveries per annum had a significant influence on the frequency of EA (<500 deliveries/year: 12.7%, 500-1000/year: 18.6%, >1,000/year: 21.6%). The preferred local anaesthetics were ropivacaine und bupivacaine. When an opioid was given this was almost always sufentanil. In 16% of the responding hospitals adrenaline was added to the epidural test bolus. CONCLUSION: EA is the mainstream method of relieving labour pains in almost all German hospitals, but is used significantly more often in hospitals with rather high numbers of yearly deliveries than in hospitals in which there are few deliveries per year.

Efficacy and safety of pregabalin in treatment refractory patients with various neuropathic pain entities in clinical routine.

AIMS: Conventional approaches to the management of neuropathic pain (NeP) often yield unsatisfactory results. We aimed to investigate pregabalin, a gamma-aminobutyric acid (GABA)-analogue, in a wide range of pregabalin naive patients with treatment refractory NeP. METHODS: Investigator-initiated, 4-week, open, prospective multicentre study in tertiary care. Pregabalin was prescribed at physicians' discretion based on patients' individual responses and tolerability, with or without concomitant analgesics. Consecutive patients were requested to fill in questionnaires at baseline and after 14 and 28 days with numerical pain rating scales (0, none; 10, worst possible), sleep rating scales, parts of the Brief Pain Inventory, Pain Experience Scale, Short Questionnaire on Current Burden and the SF-12 health-related quality of life scale. RESULTS: In 55 patients, the mean pregabalin dose was 142 +/- 26 mg at day 1 and 348 +/- 161 mg at day 28. The mean pain score decreased from 6.5 +/- 1.7 to 5.5 +/- 1.9 at day 14 and to 4.9 +/- 1.8 at day 28 (-24.6%, p < 0.0001). Significant and rapid improvements were noted in the sleep interference score (p < 0.00001), Short Questionnaire on Current Burden (p < 0.01) and SF-12 (somatic score p < 0.001; psychological score p < 0.01). Pregabalin was well tolerated, and only three patients (5%) discontinued treatment prematurely. CONCLUSIONS: Our findings suggest that pregabalin is an effective and well-tolerated drug in difficult-to-treat NeP patients under daily clinical practice conditions. A flexible dosing approach appears appropriate to ensure patient compliance and treatment success.

Iontophoretic transdermal system using fentanyl compared with patient-controlled intravenous analgesia using morphine for postoperative pain management.

BACKGROUND: The fentanyl iontophoretic transdermal system (fentanyl ITS) enables needle-free, patient-controlled analgesia for postoperative pain management. This study compared the efficacy, safety, and ease of care of fentanyl ITS with patient-controlled, i.v. analgesia (PCIA) with morphine for postoperative pain management. METHODS: A prospective, randomized, multicentre trial enrolled patients in Europe after abdominal or orthopaedic surgery. Patients received fentanyl ITS (n = 325; 40.0 microg fentanyl over 10 min) or morphine PCIA [n = 335; bolus doses (standard at each hospital)] for < or =72 h. Supplemental i.v. morphine was available during the first 3 h. The primary efficacy measure was the patient global assessment (PGA) of the pain control method during the first 24 h. RESULTS: PGA ratings of 'good' or 'excellent' were reported by 86.2 and 87.5% of patients using fentanyl ITS or morphine PCIA, respectively (95% CI, -6.5 to 3.9%). Mean (sd) last pain intensity scores (numerical rating scale, 0-10) were 1.8 (1.77) and 1.9 (1.86) in the fentanyl ITS and morphine PCIA groups, respectively (95% CI, -0.38 to 0.18). More patients reported a system-related problem for fentanyl ITS than morphine PCIA (51.1 vs 17.9%, respectively). However, fewer of these problems interrupted pain control (4.4 vs 41.3%, respectively). Patients, nurses, and physiotherapists reported more favourable overall ease-of-care ratings for fentanyl ITS than morphine PCIA. Study termination rates and opioid-related side-effects were similar between groups. CONCLUSION: Fentanyl ITS and morphine PCIA were comparably effective and safe.

[Expression und function of the ORL-1 receptor on human leukocytes]. / Expression und Funktion des ORL-1-Rezeptors auf humanen Leukozyten.

BACKGROUND: The ORL-1 receptor is expressed by human leukocytes. Limited knowledge exists about the function and interaction between the nervous and immune systems. The aim of our study was to investigate the expression of the nociceptin-ORL-1 receptor system on different leukocyte subsets and the influence of the ORL-1 receptor on the intracellular production of cytokines. METHODS: Blood from healthy volunteers of different age and sex was analysed for the expression of the ORL-1 receptor by PCR and flow cytometry and the influence of nociceptin on the LPS-induced production of intracellular cytokines by flow cytometry. RESULTS: The ORL-1 receptor mRNA is expressed by granulocytes, lymphocytes and monocytes. We could also show the expression of the ORL-1 receptor protein on the cell surface of all types of white blood cells. Nociceptin has no influence on LPS-induced cytokine production in human monocytes. There was neither a difference between young and old nor between male or female volunteers. CONCLUSION: The ORL-1 receptor is expressed by all subtypes of leukocytes. The function of this receptor is not the modulation of cytokine production and requires further studies.

[Cardiac arrest caused by an ecstasy intoxication]. / Hyperdynamer Kreislaufstillstand nach Ingestion von Ecstasy.

We report about a 19 years old man, suffering from an cardiac arrest (ventricular fibrillation) caused by an ecstasy intoxication. A supraventricular tachycardia was recorded on day three after resuscitation. No pathological findings were demonstrated by coronary angiography. An slow- fast- av -nodal- reentry- tachycardia (AVNRT) was detected and successfully treated by electrical ablation of the slow pathway during electrophysiological mapping. No severe neurological deficits were found in discharge from hospital.

[Efficacy and safety of 0.1 mg of intrathecal morphine in arthroscopic knee joint surgery]. / Spinalanästhesie bei der Arthroskopie des Kniegelenks. Effektivität und Sicherheit von Morphin 0.1 mg als Zusatz--Eine doppelblinde, randomisierte Untersuchung.

BACKGROUND AND OBJECTIVE: Intrathecal morphine provides effective postoperative analgesia but is associated with the risk of respiratory depression. A dose of only 0.1 mg has been shown to be optimal for effective and safe pain relief after abdominal surgery. This study was designed to determine whether the addition of 0.1 mg of morphine to the local anesthetic for spinal anesthesia produces adequate analgesia following arthroscopic knee joint surgery. METHODS: A prospective, randomized, placebo-controlled, double-blind clinical trial was performed. Forty ASA I/II patients undergoing knee arthroscopy under spinal anesthesia were randomized to receive either mepivacaine 4% with 0.1 mg of morphine or mepivacaine 4% with saline (placebo) intrathecally. Postoperative analgesia consisted of intravenous morphine delivered by patient-controlled analgesia (bolus: 2 mg, lockout time: 5 min). During the study period of 24 h, pain intensity at rest and on movement (visual analogue scale, 0: no pain, 100: maximum pain), vigilance, and vital parameters were recorded every hour. RESULTS: There were no statistically significant differences between the two groups in postoperative pain scores, morphine requirements, vigilance, blood pressure, heart rate, and breathing frequency. The patients of the morphine group required 12.3+/-10.2 mg (mean+/-SD) and those of the placebo group 11.6+/-8.4 mg of intravenous morphine from patient-controlled analgesia. The pain scores at rest and on movement were 10.0+/-8.1 and 16.0+/-12.6 in the morphine group and 8.2+/-7.9 and 11.7+/-11.3 in the placebo group. We did not observe severe side effects in any of the patients. CONCLUSION: Intrathecal administration of 0.1 mg of morphine does not contribute to postoperative analgesia after arthroscopic knee joint surgery.

[Effectiveness and results of intraoperative neuromonitoring in thyroid surgery. Statement of the Interdisciplinary Study Group on Intraoperative Neuromonitoring of Thyroid Surgery]. / Zuverlässigkeit und Konsequenzen des intraoperativen Neuromonitorings in der Schilddrüsenchirurgie. Stellungnahme der "Interdisziplinären Studiengruppe Intraoperatives Neuromonitoring Schilddrüsenchirurgie"

Intraoperative neuromonitoring (IONM) has yielded an increasing effect on thyroid surgery. During IONM, the recurrent laryngeal nerve is stimulated electrically and an acoustically transformed electromyographic signal is derived via either a needle electrode placed in the vocalis muscle or an electrode adjusted to the intubation tube. The IONM is used for identifying and predicting the function of the recurrent laryngeal nerve. Especially under difficult anatomic conditions, IONM has proven a valuable tool for identification of recurrent laryngeal nerves. This can lead to decreased occurrence of nerve palsy rates, as shown in numerous studies. The reliability of the IONM signal (defined as the correlation between intraoperative signal interpretation and postoperative vocal cord function) is reflected by a specificity as high as 98.2%, as shown by German multicenter studies. Thus, normal vocal cord function could be demonstrated postoperatively in over 98.2% of patients with intraoperatively unchanged neuromonitoring signals. If the neuromonitoring signal changed during operation, 39% of the patients suffered from transient vocal cord immobility and 12% had permanent loss of vocal cord function.

[Regulation of spinal nociceptin expression by neuropathic pain]. / Regulation der spinalen Expression von Nociceptin unter neuropathischen Schmerzen.

Nociceptin is the endogenous ligand of a new opioid receptor, the opioid receptor-like-1 (ORL1) receptor. Chronic inflammatory pain causes an increase in the expression of nociceptin and the ORL1 receptor in the dorsal horn of rat spinal cord, thus indicating an involvement of the endogenous nociceptin/ORL1 system in mechanisms of pathological pain. This study investigates the influence of neuropathic pain on the expression of nociceptin using immunohistochemistry. To induce neuropathic pain, a ligation of the sciatic nerve was performed in 12 rats under general anesthesia. A sham operation was performed in 12 rats of the control group. Nerve ligation caused a significant ipsilateral thermal hyperalgesia, a typical sign of neuropathic pain. The paw withdrawal latency was decreased by 45.7+/-4.9% ( p<0.05) at day 5 and by 37.3+/-1.8% ( p<0.05) at day 10. Although hyperalgesia was fully present after 5 days, no changes in nociceptin immunoreactivity in the lumbar spinal cord were detected at this time point. Ten days after nerve ligation, there was a 2.46+/-0.38 fold ( p<0.05) bilateral increase in nociceptin immunoreactivity in the lamina superficiales (I and II), with a notable increase in the inner lamina II at the level of L4. Further investigations are necessary to elucidate the relationship between neuropathic pain, the nociceptin-ORL1 receptor system and potential therapeutic options.