Surgeon experience affects perioperative pain in cats undergoing elective ovariohysterectomy: a randomized clinical trial.

OBJECTIVE: This study aimed to compare the outcomes between surgeries performed by either experienced or inexperienced surgeons by assessing intraoperative nociception and perioperative analgesia. METHODS: 16 healthy, client-owned female cats were randomly allocated into 2 groups of 8: one undergoing surgery by an experienced surgeon (GES group) and the other by inexperienced surgeons (GIS group). Both groups received IM premedication with acepromazine (0.05 mg/kg) and methadone (0.3 mg/kg). After 20 minutes, venipuncture and induction with propofol (dose-response, IV) were performed. Maintenance was achieved with inhaled isoflurane. Intraoperative vital parameters were monitored, and fentanyl (2.5 µg/kg, IV) was administered as rescue analgesia when needed. Postoperatively, pain was assessed with a visual analog scale and the multidimensional pain scale of the Universidade Estadual Paulista in Botucatu; morphine (0.2 mg/kg, IM) was used for rescue analgesia, as necessary. RESULTS: In the GIS group, significant increases in heart rate and systolic blood pressure were noted during surgery, especially during pedicle clamping. Respiratory rate and end-tidal isoflurane levels were higher in the GIS group at specific surgical stages. Survival analysis indicated that the GIS group had a greater need for fentanyl. Postoperative pain scores were generally low, but a higher proportion of GIS cats required rescue analgesia. CONCLUSIONS: Surgeon experience influences intraoperative parameters and fentanyl consumption. Inexperienced surgeons contribute to increased postoperative pain and poorer wound healing outcomes in cats undergoing elective ovariohysterectomy. CLINICAL RELEVANCE: Ovariohysterectomy is a common procedure in veterinary practice, and surgical expertise significantly impacts pain management and recovery. Yet, its effects have been underexplored, potentially compromising animal welfare.

Opioid free versus opioid sparing strategies for multimodal antinociception during laparoscopic colectomy: a randomised controlled trial.

BACKGROUND: It remains unclear whether opioid-free anesthesia (OFA), when compared to opioid-sparing anesthesia (OSA), reduces postoperative opioid consumption while still providing adequate pain control. We thus tested the hypothesis that patients having an OFA strategy during laparoscopic colectomy would require less postoperative opioids when compared to an OSA strategy. METHODS: This single-center, prospective randomized controlled superiority trial, randomly allocated consecutive patients undergoing laparoscopic colectomy to receive either sevoflurane-dexmedetomidine anesthesia with a continuous infusion of lidocaine and ketamine (OFA group) or sevoflurane-sufentanil boluses anesthesia with a continuous infusion of lidocaine (OSA group). Both groups received multimodal antinociception with boluses of dexamethasone, lidocaine, and ketamine during anesthesia induction, as well as acetaminophen, ketoprofen, and nefopam before the end of the surgery. OFA patients also received a dose of magnesium sulfate during induction. The primary outcome was cumulative opioid consumption at 48 h after surgery, expressed in oral morphine equivalents (OME). Secondary exploratory outcomes were pain scores, opioid-related adverse events, and patient quality of life (WHODAS score). RESULTS: Of the 160 randomized patients, 155 were included in a modified intention-to-treat analysis. Median [Q1-Q3] OME consumption at 48 hours after surgery did not differ between groups (9 [0-30] mg for OFAvs. 14 [0-30] mg for OSA; p = 0.861). Key secondary outcomes were not different between groups except a three time higher incidence of bradycardia in the OFA group. CONCLUSIONS: In patients undergoing laparoscopic colectomy with a multimodal antinociception protocol, OFA, when compared to OSA, did not decrease postoperative opioid consumption. CLINICAL TRIAL REGISTRY AND NUMBER: NCT05031234.

Antinociceptive and antineuropathic effects of Trifolium resupinatum L. on formalin-induced nociception and cervical spinal cord hemi-contusion: Underlying Mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Trifolium resupinatum L. (Fabaceae), known as Persian clover, ethnomedicinally used in Persian folk medicine to treat peritoneal inflammation, rheumatism, and back pain. AIM OF THE STUDY: To investigate the antineuropathic and antinociceptive activities of Trifolium resupinatum leaves essential oil (TREO) in male Wistar rats, as well as to explore the potential mechanisms of action. MATERIALS AND METHODS: The antinociceptive activity of TREO and its main constituents, quercetin (Qc) was assessed using the formalin-induced paw licking test. Moreover, the potential mechanisms of antinociception were evaluated through various competitive and non-competitive antagonisms. Additionally, the antineuropathic potential was investigated using the cervical spinal cord hemi-contusion (CCS) model, and the role of phosphorylated Stat-3 was analyzed using Western blotting. RESULTS: TREO exerted significant antinociceptive activity (P < 0.01) in both phases of the formalin-induced test; however, its effects were more pronounced in the second phase. Modulators of the NO-cGMP-K+ channel pathway significantly reversed the antinociceptive activity of TREO (P < 0.05). Additionally, antagonists of TRPV1 and TRPV2, as well as CB1 and GABAA receptors, significantly reversed the antinociceptive effects of TREO (P < 0.05). In another study, both TREO and Qc significantly attenuated hyperalgesia and mechanical allodynia (P < 0.01) when evaluated using the CCS-induced nociception model. Notably, TREO also reduced the expression levels of interleukin-1 beta, interleukin-2, and tumor necrosis factor alpha in CCS-induced rats (P < 0.05). CONCLUSION: TREO and Qc exhibit both antinociceptive and anti-neuropathic activities. The antinociceptive effects are partially mediated through the NO-cGMP-K+ channel pathways, along with the activation of TRPV, GABA, and cannabinoid receptors. Furthermore, the anti-neuropathic activity of TREO may be partially regulated through the inhibition of cytokines.

Nociception level index-directed superficial parasternal intercostal plane block vs erector spinae plane block in open-heart surgery: a propensity matched non-inferiority clinical trial.

This single-center study explored the efficacy of superficial parasternal intercostal plane block (SPIPB) versus erector spinae plane block (ESPB) in opioid-sparing within Nociception Level (NOL) index-directed anesthesia for elective open-heart surgery. After targeted propensity matching, 19 adult patients given general anesthesia with preincisional SPIPB were compared to 33 with preincisional ESPB. We hypothesized that SPIPB is non-inferior to ESPB in reducing total intraoperative fentanyl consumption, with a non-inferiority margin (δ) set at 0.1 mg. Intraoperative fentanyl dosing targeted a NOL index ≤ 25. Postoperatively, paracetamol 1 g 6-hourly and morphine for numeric rating scale (NRS) ≥ 4 were administered. This study could not demonstrate that SPIPB was inferior to ESPB for total intraoperative fentanyl consumption, as the confidence interval for the median difference of 0.1 mg (95% CI 0.05-0.15) crossed the predefined δ, with the lower bound falling below and the upper bound exceeding δ, p = 0.558. SPIPB led to higher postoperative morphine use at 24 and 48 h: 0 (0-40.6) vs. 59.5 (28.5-96.1) µg kg-1, p < 0.001 and 22.2 (0-42.6) vs. 63.5 (28.5-96.1) µg kg-1, p = 0.001. Four times fewer SPIPB patients remained morphine-free at 48 h, p < 0.001, and their time to first morphine dose was three times shorter compared to ESPB patients, p = 0.001. SPIPB led to higher time-weighted average NRS scores at rest, 1 (0-1) vs. 1 (1-2), p = 0.004, and with movement, 2 (1-2) vs. 3 (2-3), p = 0.002, calculated over the 48-h period post-extubation. The SPIPB group had a significantly higher average NOL index, p = 0.003, and greater NOL index variability, p = 0.027. This study could not demonstrate that SPIPB was inferior to ESPB for intraoperative fentanyl consumption. Significant differences were observed in secondary outcomes, with SPIPB leading to higher postoperative morphine use, higher pain scores, and reduced nociception control.

Assessment of the antinociceptive effect of a single fentanyl bolus dose in children: A pharmacokinetic and pharmacodynamic analysis based on the nociception level index during sevoflurane general anesthesia.

BACKGROUND: The Nociception Level Index has shown benefits in estimating the nociception/antinociception balance in adults, but there is limited evidence in the pediatric population. Evaluating the index performance in children might provide valuable insights to guide opioid administration. AIMS: To evaluate the Nociception Level Index ability to identify a standardized nociceptive stimulus and the analgesic effect of a fentanyl bolus. Additionally, to characterize the pharmacokinetic/pharmacodynamic relationship of fentanyl with the Nociception Level Index response during sevoflurane anesthesia. METHODS: Nineteen children, 5.3 (4.1-6.7) years, scheduled for lower abdominal or urological surgery, were studied. After sevoflurane anesthesia and caudal block, a tetanic stimulus (50 Hz, 60 mA, 5 s) was performed in the forearm. Following the administration of fentanyl 2 µg/kg intravenous bolus, three similar consecutive tetanic stimuli were performed at 5-, 15-, and 30-min post-fentanyl administration. Changes in the Nociception Level Index, heart rate, mean arterial pressure, and bispectral index were compared in response to the tetanic stimuli. Fentanyl plasma concentrations and the Nociception Level Index data were used to elaborate a pharmacokinetic/pharmacodynamic model using a sequential modeling approach in NONMEM®. RESULTS: After the first tetanic stimulus, both the Nociception Level Index and the heart rate increased compared to baseline (8 ± 7 vs. 19 ± 10; mean difference (CI95) -12(-18--6) and 100 ± 10 vs. 102 ± 10; -2(-4--0.1)) and decrease following fentanyl administration (19 ± 10 vs. 8 ± 8; 12 (5-18) and 102 ± 10 vs. 91 ± 11; 11 (7-16)). In subsequent tetanic stimuli, heart rate remained unchanged, while the Nociception Level Index progressively increased within 15 min to values similar to those before fentanyl. An allometric weight-scaled, 3-compartment model best characterized the pharmacokinetic profile of fentanyl. The pharmacokinetic/pharmacodynamic modeling analysis revealed hysteresis between fentanyl plasma concentrations and the Nociception Level Index response, characterized by plasma effect-site equilibration half-time of 1.69 (0.4-2.9) min. The estimated fentanyl C50 was 1.93 (0.73-4.2) ng/mL. CONCLUSION: The Nociception Level Index showed superior capability compared to traditional hemodynamic variables in discriminating different nociception-antinociception levels during varying fentanyl concentrations in children under sevoflurane anesthesia.

Characterization of a rapid avoidance behavior in Manduca sexta larvae in response to noxious stimuli.

This study focuses on the nociceptive responses observed in the tobacco hornworm (Manduca sexta). While prior investigations have described the sensory neurons and muscle activation patterns associated with the 'strike' behavior, there remains a gap in our understanding of the alternative 'withdrawal' movement, wherein the animal bends its head and thorax away from the stimulus. Our results show that stimulus location determines which nocifensive behavior is elicited. Interestingly, stimulation of specific mid-body segments could result in either withdrawal or strike, indicating a decision process rather than a hard-wired circuit. The withdrawal behavior was characterized using high-speed videography and electromyography. The results show that withdrawal in Manduca is driven by contralateral ventral muscles, followed by an increase in ipsilateral muscle activation just before the bending stops. Dorsal muscles are co-activated throughout the movement. Although both withdrawal and strike behaviors involve sequential activation of lateral muscles, these behaviors involve different muscle groups. This discovery provides a novel model system to investigate the context-dependence and decision-making processes triggered by stressful or noxious stimuli.

Impact of deep neuromuscular blockade on intraoperative NOL-guided remifentanil requirement during desflurane anesthesia in laparoscopic colorectal surgeries: A randomised controlled trial.

STUDY OBJECTIVE: Evaluate the impact of deep neuromuscular blockade on intraoperative nociception Deep neuromuscular blockade has been shown to improve surgical conditions and postoperative outcomes compared to moderate neuromuscular blockade in laparoscopic surgery. Still, its impact on intraoperative nociception and opioid requirement has never been assessed. DESIGN: Monocentric randomised controlled trial. SETTING: Operating room. PATIENTS: We included 100 ASA I to III patients who underwent colorectal laparoscopic surgery with desflurane-remifentanil anesthesia. INTERVENTIONS: Patients were randomised into two groups to achieve either moderate (1-3 train of four response) or deep (1-2 post-tetanic count) neuromuscular block (NMB) with repeated boluses of rocuronium. The Nociception Level (NOL) index guided intraoperative remifentanil administration in both groups. MEASUREMENTS: The primary endpoint was total intraoperative remifentanil administration per hour of surgery. Secondary endpoints included, Leiden Surgical Rating Scale (L-SRS), intra-abdominal pressure, postoperative pain scores and opioids' consumption. MAIN RESULTS: Ninety-three patients were analysed. Forty-five in the deep group and 48 patients in moderate group. Intraoperative administration of remifentanil was 348 (228-472) µg.h-1 in the deep NMB group compared to 494 (392-618) µg.h-1 in the moderate NMB group (P < 0.001). Lowest L-SRS was 5 (4-5) in the deep NMB group versus 3 (2-5) (P < 0.001) in the moderate NMB group. Mean intra-abdominal pressure was 11.9 (1.3) in the deep NMB group versus 13 (1.3) (P < 0.001) in the moderate NMB group. Secondary postoperative outcomes including pain scores and analgesics administration were not significantly different. CONCLUSIONS: This study shows that deep neuromuscular blockade reduces intraoperative NOL-guided administration of remifentanil in colorectal laparoscopic surgeries. It also improves surgical conditions. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov under NCT03910998.

Nuclear Magnetic Resonance Treatment Induces ßNGF Release from Schwann Cells and Enhances the Neurite Growth of Dorsal Root Ganglion Neurons In Vitro.

Peripheral nerve regeneration depends on close interaction between neurons and Schwann cells (SCs). After nerve injury, SCs produce growth factors and cytokines that are crucial for axon re-growth. Previous studies revealed the supernatant of SCs exposed to nuclear magnetic resonance therapy (NMRT) treatment to increase survival and neurite formation of rat dorsal root ganglion (DRG) neurons in vitro. The aim of this study was to identify factors involved in transferring the observed NMRT-induced effects to SCs and consequently to DRG neurons. Conditioned media of NMRT-treated (CM NMRT) and untreated SCs (CM CTRL) were tested by beta-nerve growth factor (ßNGF) ELISA and multiplex cytokine panels to profile secreted factors. The expression of nociceptive transient receptor potential vanilloid 1 (TRPV1) channels was assessed and the intracellular calcium response in DRG neurons to high-potassium solution, capsaicin or adenosine triphosphate was measured mimicking noxious stimuli. NMRT induced the secretion of ßNGF and pro-regenerative-signaling factors. Blocking antibody experiments confirmed ßNGF as the main factor responsible for neurotrophic/neuritogenic effects of CM NMRT. The TRPV1 expression or sensitivity to specific stimuli was not altered, whereas the viability of cultured DRG neurons was increased. Positive effects of CM NMRT supernatant on DRG neurons are primarily mediated by increased ßNGF levels.

The relationship of pain catastrophizing in principal caregivers of postoperative children with malignant bone tumors and children's kinesiophobia and pain perception: A cross-sectional survey.

OBJECTIVE: To examine the phenomenon of pain catastrophizing among the principal caregivers of postoperative children with malignant bone tumors and explore its impact on pain perception and kinesiophobia in children. DESIGN: A cross-sectional study design. METHODS: Using a cross-sectional study design, a questionnaire-based survey was conducted among 140 children with malignant bone tumors and their principal caregivers, who were admitted to a tertiary hospital in Shanghai from 2020 to 2023. Pearson's univariate and multiple regression analyses were conducted. The questionnaire included general data, the Parental Pain Catastrophizing Scale, the Short-Form McGill Pain Questionnaire, and the Tampa Scale of Kinesiophobia. RESULTS: The frequency of pain catastrophizing for the principal caregivers was 16.8%. The frequency of kinesiophobia in children was 93.1%. The level of pain catastrophizing was positively correlated with the level of kinesiophobia and pain perception (r = 0.556, 0.614, p < 0.05). Multiple logistic regression analysis showed that the level of pain catastrophizing in principal caregivers was an important factor of kinesiophobia in children (B = 0.370, Std. = 0.119, Wald = 9.687, Ex (P) = 1.448, p = 0.002). Multiple linear regression analysis showed that the incidence of pain catastrophizing and the level of kinesiophobia were important influencing factors in pain perception (p < 0.05), with R2 = 0.272, adjusted R2 = 0.249, F = 11.579, and p < 0.001. CONCLUSIONS: The level of pain catastrophizing in the principal caregivers was an important factor in postoperative kinesiophobia and pain perception in children with a malignant bone tumor. PRACTICE IMPLICATIONS: It is important to evaluate the patients' and their families' emotional changes and psychological needs during the perioperative period. Nurses play a crucial role in providing appropriate interventions for patients or families to reduce the negative pain experience and improve patients' prognosis.

The Anti-Arthritic Potential of the Ethanolic Extract of Salvia Lachnostachys Benth. Leaves and Icetexane Dinor-Diterpenoid Fruticuline B.

The decoction of Salvia lachnostachys Benth. leaves is used in Brazilian folk medicine for anti-spasmodic, antipyretic, and anxiolytic purposes. Some of the biological effects of an S. lachnostachys extract have been shown to be anti-inflammatory, anti-cancer, and antidepressant effects. In addition, this medicinal plant produces several compounds including icetexane diterpenoids, such as fruticuline A and fruticuline B. The aim of the present work was to evaluate the anti-hyperalgesic and anti-inflammatory properties of fruticuline B (FRUT B) and the ethanolic extract obtained from the leaves of S. lachnostachys (EESL) in experimental mouse models. EESL (30, 100, and 300 mg/kg) and FRUT B (1 mg/kg) were evaluated in articular inflammation-induced models in Swiss mice. In articular inflammation induced by Zymosan, EESL (300 mg/kg) and FRUT B (1 mg/kg) significantly reduced mechanical hyperalgesia (83.17% inhibition for EESL and 81.19% for FRUT B); edema (68.75% reduction for EESL and 33.66% for FRUT B); leukocyte migration (81.3% for EESSL and 92.2% for FRUT B), and nitric oxide production (88.3% for EESL and 74.4% for FRUT B). The exposure to fruticuline B significantly inhibited the edema (51.5%), mechanical (88.12%) and cold hyperalgesia (80.8%), and myeloperoxidase (MPO) (63.4%) activity 24 h after CFA injection. In the pleurisy model, FRUT B reduced 89.1% of leukocyte migration and 50.3% in nitric oxide production. Four hours after carrageenan injection, FRUT B (1 mg/kg) diminished 89.11% of mechanical hyperalgesia, 65.8% of paw edema, and 82.12% of the response to cold hyperalgesia. In the MTT test, EESL and fruticuline B caused no cytotoxicity. The present study revealed, for the first time, the anti-arthritic and anti-nociceptive effects of FRUT B, pointing out the therapeutic potential of the species to control inflammation and nociception. Future studies are needed to evaluate other biological properties of fruticuline B and to better understand its mechanism of action.

Linkage of alternative exon assembly in Drosophila TrpA1 transcripts.

Drosophila TrpA1 (transient receptor potential ankyrin 1) transcripts are alternatively spliced at 2 distinct sites each with a choice of mutually exclusive exons. The first site determines exon1 encoding the amino terminus to produce either nucleophile-, electrophile- and noxious temperature-gated TRPA1(A) or electrophile- and innocuous warmth-gated TRPA1(B). The second site selects for exon10, resulting in TrpA1 variants with either exon10a or exon10b encoding a domain between the N-terminal ankyrin repeats and the transmembrane segments. Although unbiased assembly would generate TRPA1 with 4 different domain combinations, the functional impact of these alternative domains remains to be thoroughly examined. Here, we find that there is a relatively strong linkage in mRNA splicing between the 2 sites in the case of TrpA1(B), but not TrpA1(A), transcripts. Our semiquantitative assay, consisting of reverse transcription polymerase chain reaction and Sanger sequencing, revealed that exon10b is little coupled with TrpA1(B) transcripts, suggesting that only 3 isoforms, TRPA1(A)-exon10a [denoted as TRPA1(A)], TRPA1(A)-exon10b [TRPA1(A)10b], and TRPA1(B)-exon10a [TRPA1(B)], are present at detectable levels using our method. Interestingly, heterologously expressed TRPA1(A)10b showed elevated sensitivity to low concentrations of N-methyl maleimide, a cysteine-modifying electrophile, compared with other isoforms. Equivalent isoforms in malaria-transmitting Anopheles gambiae displayed a similar pattern of isoform-dependent N-methyl maleimide dose dependences, suggesting that the chemosensory regulation by selective domain assembly is conserved in insect TRPA1s. Thus, alternative RNA splicing of exon10 is coordinated in conjunction with the first exons, regulating chemical sensitivity of insect TRPA1s.

Monitoring surgical nociception using multisensor physiological models.

Monitoring nociception, the flow of information associated with harmful stimuli through the nervous system even during unconsciousness, is critical for proper anesthesia care during surgery. Currently, this is done by tracking heart rate and blood pressure by eye. Monitoring objectively a patient's nociceptive state remains a challenge, causing drugs to often be over- or underdosed intraoperatively. Inefficient management of surgical nociception may lead to more complex postoperative pain management and side effects such as postoperative cognitive dysfunction, particularly in elderly patients. We collected a comprehensive and multisensor prospective observational dataset focused on surgical nociception (101 surgeries, 18,582 min, and 49,878 nociceptive stimuli), including annotations of all nociceptive stimuli occurring during surgery and medications administered. Using this dataset, we developed indices of autonomic nervous system activity based on physiologically and statistically rigorous point process representations of cardiac action potentials and sweat gland activity. Next, we constructed highly interpretable supervised and unsupervised models with appropriate inductive biases that quantify surgical nociception throughout surgery. Our models track nociceptive stimuli more accurately than existing nociception monitors. We also demonstrate that the characterizing signature of nociception learned by our models resembles the known physiology of the response to pain. Our work represents an important step toward objective multisensor physiology-based markers of surgical nociception. These markers are derived from an in-depth characterization of nociception as measured during surgery itself rather than using other experimental models as surrogates for surgical nociception.

Decrease of the peak heights of EEG bicoherence indicated insufficiency of analgesia during surgery under general anesthesia.

BACKGROUND: Studies show that the two peak heights of electroencephalographic bicoherence (pBIC-high, pBIC-low) decrease after incision and are restored by fentanyl administration. We investigated whether pBICs are good indicators for adequacy of analgesia during surgery. METHODS: After local ethical committee approval, we enrolled 50 patients (27-65 years, ASA-PS I or II) who were scheduled elective surgery. Besides standard anesthesia monitors, to assess pBICs, we used a BIS monitor and freeware Bispectrum Analyzer for A2000. Fentanyl 5 µg/kg was completely administered before incision, and anesthesia was maintained with sevoflurane. After skin incision, when the peak of pBIC-high or pBIC-low decreased by 10% in absolute value (named LT10-high and LT10-low groups in order) or when either peak decreased to below 20% (BL20-high and BL20-low groups), an additional 1 g/kg of fentanyl was administered to examine its effect on the peak that showed a decrease. RESULTS: The mean values and standard deviation for pBIC-high 5 min before fentanyl administration, at the time of fentanyl administration, and 5 min after fentanyl administration for LT10-high group were 39.8% (10.9%), 26.9% (10.5%), and 35.7% (12.5%). And those for pBIC-low for LT10-low group were 39.5% (6.0%), 26.8% (6.4%) and 35.0% (7.0%). Those for pBIC-high for BL20-high group were 26.3% (5.6%), 16.5% (2.6%), and 25.7% (7.0%). And those for pBIC-low for BL20-low group were 26.7% (4.8%), 17.4% (1.8%) and 26.9% (5.7%), respectively. Meanwhile, at these trigger points, hemodynamic parameters didn't show significant changes. CONCLUSION: Superior to standard anesthesia monitoring, pBICs are better indicators of analgesia during surgery. TRIAL REGISTRY: Clinical trial Number and registry URL: UMIN ID: UMIN000042843 https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno = R000048907.

Preventing Postoperative Catheter-Related Bladder Discomfort (CRBD) with Bladder Irrigation Using 0.05% Lidocaine Saline Solution: Monitoring with Analgesia Nociception Index (ANI) after Transurethral Surgery.

(1) Background and Objectives: Catheter-related bladder discomfort (CRBD), a common and distressing consequence of indwelling urinary catheters, can significantly impact postoperative recovery. This study aimed to determine the effectiveness of bladder irrigation with a 0.05% lidocaine normal saline solution for the prevention of CRBD following transurethral surgery. (2) Materials and Methods: In this randomized, double-blind, placebo-controlled trial, patients were assigned to either a control group receiving normal saline or a treatment group receiving 0.05% lidocaine (2% lidocaine 25 mL in 1000 mL saline) for bladder irrigation. Both groups were administered fentanyl (1 µg/kg) for analgesia at the end of the procedure. The primary endpoint was the assessment of the incidence and severity of CRBD upon awakening within the first 6 h postoperatively, using a four-grade scale based on the patients' reports of discomfort. (3) Results: Out of 79 patients completing the study, the incidence of moderate to severe CRBD was significantly lower in the lidocaine group (5.1%, 2/39) compared to the control group (25%, 10/40) at 10 min after waking from anesthesia (p = 0.014). Furthermore, the lidocaine group experienced significantly less CRBD at 1 and 2 h postoperative (2.6% and 0%, respectively) compared to the control group (20% and 10%, respectively) (p = 0.015, p = 0.043), with no significant differences at 6 h (p = 0.317). (4) Conclusions: The results suggest that bladder irrigation with 0.05% lidocaine reduces the occurrence of moderate to severe CRBD by nearly 80% in the initial 2 h postoperative period after transurethral surgery.

Down-regulation of microRNA-382-5p reduces neuropathic pain by targeting regulation of dual specificity phosphatase-1.

Background: MicroRNA (miRNA) plays a crucial role in neuropathic pain (NP) by targeting mRNAs. This study aims to analyze the regulatory function and mechanism of miR-382-5p/dual specificity phosphatase-1 (DUSP1) axis in NP. Methods: We utilized rats with chronic constriction injury (CCI) of the sciatic nerve as the NP model. The levels of miR-382-5p and DUSP1 were reduced by intrathecal injection of lentiviral interference vectors targeting miR-382-5p and DUSP1. The mRNA levels of miR-382-5p and DUSP1 in the dorsal root ganglions (DRGs) were measured by RT-qPCR assay. The pain behavior was evaluated by mechanical nociceptive sensitivity and thermal nociceptive sensitivity. The expression levels of interleukin-6 (IL)-6, IL-1ß, and tumor necrosis factor-α in the DRGs were analyzed by ELISA assay. The targeting relationship between miR-382-5p and DUSP1 was verified by DLR assay and RIP assay. Results: Compared to the Sham group, the CCI rats exhibited higher levels of miR-382-5p and lower levels of DUSP1. Overexpression of miR-382-5p significantly decreased DUSP1 levels. Reducing miR-382-5p levels can lower the mechanical nociceptive sensitivity and thermal nociceptive sensitivity of CCI rats and inhibit the over-activation of pro-inflammatory factors. Reduced miR-382-5p levels decreased NP in CCI rats. DUSP1 is the target of miR-382-5p, and down-regulation of DUSP1 reverses the inhibitory effect of reduced miR-382-5p levels on NP. Conclusions: Down-regulation of miR-382-5p inhibits the over-activation of pro-inflammatory factors by targeting and regulating the expression of DUPS1, thereby alleviating NP.

High frequency variability index in predicting postoperative pain in video/robotic-assisted thoracoscopic surgery under combined general anesthesia and peripheral nerve block: an observational study.

The high frequency variability index (HFVI)/analgesia nociception index (ANI) is purported to assess the balance between nociception and analgesia in patients under general anesthesia. This observational study investigated whether intraoperative HFVI/ANI correlates with postoperative pain in patients performed with nerve block under general anesthesia in video/robotic-assisted thoracoscopic surgery (VATS/RATS). We investigated whether maximum postoperative pain at rest and postoperative morphine consumption are associated with HFVI/ANI just before extubation, mean HFVI/ANI during anesthesia, the difference in HFVI/ANI between before and 5 min after the start of surgery, and the difference in HFVI/ANI between before and 5 min after the nerve block. Data obtained from 48 patients were analyzed. We found no significant association between HFVI/ANI just before extubation and postoperative Numerical Rating Scale (NRS) score. Receiver operating characteristic curve analysis revealed that moderate (NRS > 3) or severe (NRS > 7) postoperative pain could not be predicted by HFVI/ANI just before extubation. In addition, there were no associations between postoperative morphine consumption and HFVI/ANI at any time points. The present study demonstrated that it is difficult to predict the degree of postoperative pain in patients undergoing VATS/RATS under general anesthesia combined with peripheral nerve block, by using HFVI/ANI obtained at multiple time points during general anesthesia.

Analysis of the Effects of Epidural Anesthesia on the Nociception Level Index (NOL®) during Abdominal Surgery.

Background: The NOL® system (PMD-200™ Nociception Level Monitor; Medasense Ltd., Ramat Gan, Israel) is used for the real-time detection of physiological nociception in anesthetized patients by assessing the parameters indicative of sympathetic activity, such as photoplethysmography, skin conductance, peripheral temperature, and accelerometry, which are quantified into the NOL®-Index. This index is more sensitive than traditional clinical parameters in estimating pain and stress responses. While its effectiveness in general anesthesia is well documented, its efficacy in epidural anesthesia needs further investigation. Methods: This retrospective study analyzed NOL®-Index dynamics compared to conventional parameters after epidural administration of bupivacaine. Following ethics committee approval, 119 NOL® measurements were retrospectively analyzed after thoracic epidural catheter administration in 40 patients undergoing abdominal and urological surgery. The NOL-Index® was assessed at 0, 1, 3, and 5 min post application and compared to heart rate, blood pressure, and bispectral index dynamics. Results: This study showed a significant decrease in the NOL®-Index post-local-anesthetic administration with better sensitivity than classical clinical parameters (0 min = 38 ± 11; 1 min = 22 ± 13*; 3 min = 17 ± 11*; 5 min = 12 ± 10*). Higher doses of local anesthetics led to a significant, dose-dependent decrease in NOL®-Index (low dose, 5 min = 15 ± 10*; high dose, 5 min = 8 ± 8*). Conclusions: This study is the first to demonstrate the effectiveness of the NOL®-Index in measuring nociceptive effects following epidural administration, highlighting its potential superiority over conventional parameters and its sensitivity to dose variations.

Evaluation of the Therapeutic Potential of Amantadine in a Vincristine-Induced Peripheral Neuropathy Model in Rats.

This study aimed to evaluate the therapeutic potential of amantadine in a vincristine-induced peripheral neuropathy model in rats. Forty-eight male Wistar rats were used. The treated groups received oral amantadine at doses of 2, 5, 12, 25 and 50 mg/kg, with daily applications for 14 days. The mechanical paw withdrawal threshold was measured using a digital analgesimeter. Immunohistochemical analysis of IL-6, TNFα, MIP1α, IL-10, CX3CR1, CXCR4, SOD, CAT and GPx, and enzymatic activity analysis of CAT, SOD and GPx were performed, in addition to quantitative PCR of Grp78, Chop, Ho1, Perk, Bax, Bcl-xL, Casp 3, Casp 9, IL-6, IL-10, IL-18 and IL-1ß. The results showed an increase in nociceptive thresholds in animals that received 25 mg/kg and 50 mg/kg amantadine. Immunohistochemistry showed a decrease in the immunostaining of IL-6, TNFα, MIP1α and CX3CR1, and an increase in IL-10. CAT and SOD showed an increase in both immunochemistry and enzymatic analysis. qPCR revealed a reduced expression of genes related to endoplasmic reticulum stress and regulation in the expression of immunological and apoptotic markers. Amantadine demonstrated antinociceptive, anti-inflammatory and antioxidant effects in the vincristine-induced peripheral neuropathy model in rats, suggesting that amantadine may be considered an alternative approach for the treatment of vincristine-induced peripheral neuropathic pain.

Assessment of the nociceptive response to the use of cannabidiol alone and in combination with meloxicam through infrared pupillometry in female dogs undergoing elective ovariohysterectomy.

The negative effects of pain are a constant concern in the surgical management of animals, leading to the search for new drugs or more effective analgesic protocols to control this negative emotion. This study aimed to evaluate the nociceptive response of cannabidiol (CBD) alone and in combination with meloxicam using infrared pupillometry in female dogs undergoing elective ovariohysterectomy (OVH) under isoflurane anesthesia. A total of 60 female dogs of different breeds were included. These dogs were randomly assigned to four study groups according to the treatment: Control Group (G0: n = 15) receiving saline solution; group premedicated with meloxicam at a dose of 0.2 mg Kg-1 IV (GMelox: n = 15). Postoperatively this drug was used at 0.1 mg Kg-1 IV every 24 h; the CBD-treated Group (GCBD: n = 15) at a dose of 2 mg Kg-1 orally in the preoperative. Postoperatively was administrated every 12 h; and the Group premedicated with the combination of meloxicam and CBD (GMelox/CBD: n = 15) Meloxicam at a dose of 0.2 mg Kg-1 IV preoperatively, and 0.1 mg Kg-1 IV during the postoperative. CBD at a dose of 2 mg Kg-1 orally in the preoperative, and every 12 h in the postoperative. Treatments were administered for 48 postoperative hours. After OVH, the pupillary neurologic index, pupillary size, minimum diameter (MIN), percentage change, constriction latency (Lat), constriction velocity, and maximum constriction velocity were recorded as pupillometric variables in both eyes during events (E): Baseline (30 min before drug administration), E30 min, E1h, E2h, E3h, E4h, E8h, E12h, E24h, and E48h. The Short-Form of the Glasgow Composite Measure Pain Scale (GCMPS-SF) was used to assess pain during the same events. Overall, it was observed that the pupillometric variables Size, MIN., and Lat. were significantly higher in G0 compared to the other groups during E30 min, E1h, and E2h (p = 0.03), indicating greater pupil dilation in G0 animals. Additionally, no statistically significant differences were observed in GCMPS-SF between GMelox, GCBD, and GMelox/CBD during the postoperative period (p > 0.05). In contrast, the scores were statistically different compared to G0 (p = 0.00001), where all animals in this group received rescue analgesia at 2 h post-surgery. According to pupillometry and scores on the GCMPS-SF scale, it was observed that monotherapy with cannabidiol provides a similar analgesic effect to meloxicam alone or in combination with cannabidiol to manage acute pain in dogs. Similarly, these findings suggest that infrared pupillometry could be a tool for recognizing acute pain in dogs.

Comparison of analgesia nociception index, surgical pleth index and hemodynamic parameters between patients receiving fentanyl versus dexmedetomidine analgesia for supratentorial craniotomy - an open label active-controlled randomized trial.

Dexmedetomidine decreases heart rate (HR) and increases high frequency (HF) component of HR variability (HRV). Analgesia Nociception Index (ANI) measures nociception by analyzing the influence of respiration on HF component of HRV while surgical pleth index (SPI) derives this information from photoplethymographic signals of finger arterioles. Therefore, during administration of dexmedetomidine, reliability of ANI may vary. This study compared the changes in ANI, SPI and hemodynamics (HR and mean arterial pressure [MAP]) during various noxious stimuli with fentanyl and dexmedetomidine intraoperative analgesia. In this trial, patients undergoing elective supratentorial surgery under general anesthesia were randomized to receive either fentanyl or dexmedetomidine infusion for intraoperative analgesia. ANI (instantaneous and mean), SPI, HR and MAP were compared before and after noxious stimuli (intubation, skull pin insertion, skin incision and craniotomy) with respect to magnitude of maximum change in the variable and the time taken for the maximal change (defined as response time) between the groups. A total of 58 patients, 29 in each group were recruited into the study. At intubation, SPI changed significantly more in the fentanyl group compared to dexmedetomidine group (37 versus 20 units, p = 0.007). At skull pinning, ANI values (both instantaneous and mean) changed more in dexmedetomidine group (p = 0.024 and 0.009) with significantly longer response time (p = 0.039). There was no difference between the groups with respect to any of the variables at skin incision and craniotomy. ANI during use of dexmedetomidine and SPI while using fentanyl, might be the better choices as intraoperative nociception monitors.