OBJECTIVE: To assess the importance of appropriate opioid administration methods according to nociceptive monitoring.
METHODS: We conducted a randomized controlled trial involving 54 patients who underwent robot-assisted laparoscopic radical prostatectomy at our hospital. Patients were randomly allocated to either receive nociception level (NOL)-directed intraoperative opioid management with a minimum flow of remifentanil (NOL group) or conventional intraoperative analgesic management (control group). The primary outcome was the mean intraoperative remifentanil infusion flow rate (intraoperative remifentanil usage [μg]/ideal body weight [kg]/operation time [min]). The main secondary outcomes were plasma concentrations of three perioperative inflammatory biomarkers (interleukin-6, C-reactive protein [CRP], and cortisol levels) and postoperative pain (Numeric Rating Scale [NRS]) scores 2 h postoperatively and on postoperative days 1, 2, 3, and 7.
RESULTS: Compared with standard analgesia management, NOL-directed analgesic management reduced remifentanil consumption by 20% ( - 0.038; 95% confidence interval, - 0.059 to - 0.017; p = 0.0007). NOL-directed management did not lead to an increase in IL-6, CRP, or cortisol levels compared with conventional analgesic management. Furthermore, this protocol led to improvements in the NRS scores at rest 2 h postoperatively and upon movement up to postoperative day 3.
CONCLUSIONS: NOL-directed analgesic management reduced remifentanil consumption by 20% and the NRS scores at rest 2 h postoperatively and upon movement up to postoperative day 3 without an increase in inflammatory marker levels.
UNASSIGNED: Japan Registry of Clinical Trials, JRCTs052220034.

BACKGROUND: Effective pain management is vital in critical care settings, particularly post-surgery. Clinicians should maintain objective and efficient standards to assess pain in a patient-centered manner, in order to effectively manage this complex issue. A newer technology, the nociception level (NOL) index, shows promise in achieving this task through its multi-parameter evaluation.
METHODS: This study was a prospective, controlled, randomized trial involving two groups of patients (n=30 each) in a diverse intensive care unit. Participants were over 18 years old with American Society of Anesthesiology scores ranging from I to III and were scheduled for critical care follow-up after general anesthesia. All subjects followed a standard analgesia protocol that included rescue analgesia. Drug administration was guided by a numeric rating scale and the critical care pain observation tool in the Control Group, while it was guided by nociception level index monitoring in the NOL Group.
RESULTS: Pain scores between the two groups did not significantly differ. However, within the NOL Group, pain scores and noci-ception values displayed a strong positive correlation. Notably, total analgesic consumption was significantly lower in the NOL Group (p=0.036).
CONCLUSIONS: Monitoring pain using the nociception level index is an effective method for detecting pain compared to standard pain scores utilized in critical care. Its guidance facilitates personalized analgesic titration. Additionally, the potential of nociception level index guidance to reduce the duration of intensive care and hospital stays may be linked to its effects on delirium, a connection that awaits further exploration in future studies.

Both tissue hypoperfusion and elevated surgical stress during surgery are involved in the pathogenesis of postoperative acute kidney injury (AKI). Although intraoperative hypotension, which evokes renal hypoperfusion, has been reported to be associated with the development of postoperative AKI, there is no consensus on the association between surgical stress responses (e.g., hypertension and inflammation) and postoperative AKI. Given that intraoperative values of nociceptive response (NR) index are reportedly associated with surgical stress responses, the present study was performed to assess associations between intraoperative NR index and postoperative AKI in patients undergoing non-cardiac surgery. In this single-institutional retrospective cohort study, data of the highest and lowest values of NR index during surgery were obtained in consecutive adult patients undergoing non-cardiac surgery under general anesthesia from February 2022 to August 2023. Data on highest and lowest mean blood pressure (MBP) during surgery were also obtained. In 5,765 patients enrolled, multivariate regression analysis revealed that the development of early postoperative AKI was significantly associated with highest NR during surgery ≥ 0.920, lowest MBP during surgery < 54 mmHg, age ≥ 48 years, male sex, ASA-PS ≥ III, emergency, and duration of surgery ≥ 226 min. In addition to intraoperative hypotension, a higher level of intraoperative NR index is likely associated with higher incidence of early postoperative AKI in adult patients undergoing non-cardiac surgery under general anesthesia.

The aim of this prospective clinical study was to evaluate the efficacy of the Surgical Pleth Index (SPI), a validated nociception monitor in human anaesthesia, in dogs. The technology uses a plethysmographic signal from a specific pulse oximetry probe to analyse pulse wave amplitudes and heartbeat intervals. Twenty-six healthy dogs anaesthetised for castration were included. SPI, invasive mean arterial pressure (MAP) and heart rate (HR) were continuously monitored. The occurrence or resolution of a haemodynamic reaction (HDR), defined as a > 20% increase in HR and/or MAP, was assessed at predefined times: cutaneous incision, testicles\' exteriorization, cutaneous suture, and fentanyl administration. Following nociceptive events, the dogs presenting a HDR showed a significant 8% and 10% increase in SPI at 3 and 5 min respectively, whereas after fentanyl administration, a 13% and 16% significant decrease in SPI were noted. Receiver operating characteristic curves analysis indicated a moderate performance for the dynamic variations of SPI over 1 min to predict a HDR (AUC: 0.68, threshold value: +15%) or its resolution after fentanyl administration (AUC of 0.72, threshold value: -15%) within 3 min. The SPI varied according to perioperative nociceptive events and analgesic treatment; however, its performance to anticipate a HDR was limited with high specificity but low sensivity. Refinement of the algorithm to specifically accommodate for the canine species may be warranted. Further studies are required to evaluate the influence of other factors on the performance of this index.

UNASSIGNED: The mode of delivery might prompt a long-lasting alteration in physiological and behavioral responsiveness in offspring.
UNASSIGNED: This study was intended to evaluate if the mode of delivery could alter sensitivity to thermal and chemical stimuli in female rats.
UNASSIGNED: 56 adult female Wistar rats (200-220 gr) that were born by vaginal or cesarean section (C-section) were used (n = 28/each). Inflammatory pain was induced by subcutaneous injection of formalin into the hind paw. The thermal nociceptive threshold was determined by tail-flick and hot plate tests. Besides, the Western blot test was used to evaluate the spinal cord levels of c-Fos and c-Jun proteins.
UNASSIGNED: Formalin-induced inflammation was significantly decreased in C-section group as compared to vaginally born rats (p < 0.001). The baseline nociceptive threshed and morphine-induced analgesia were significantly increased in C-section groups in comparison to vaginally born rats. In addition, the levels of c-Fos and c-Jun proteins were significantly decreased in the spinal cord of C-section rats as compared to vaginally born animals (p < 0.01). Morphine treatment could decrease the expression of c-Fos and c-Jun in the C-section group (p < 0.05).
UNASSIGNED: Overall, C-section rats showed lower spinal nociceptive processing and neuronal activity later in life, compared to the vaginal born rats.

BACKGROUND: Low back pain (LBP) is a significant public health problem, is very prevalent, and is often characterized by the persistence of symptoms. Transcutaneous electrical nerve stimulation (TENS) may benefit people with chronic LBP because it can activate descending inhibitory pathways and inhibit central excitability. However, previous studies that have investigated the effects of TENS on pain in people with LBP have failed to use proper intensities of current, and the timing of the assessment of pain was not performed during the peak of the analgesic response or functional activities. Therefore, the present study aims to assess the effects of TENS on measures of pain, function, and descending inhibition using the maximal tolerable intensity of TENS in participants with LBP.
METHODS: This study will be a randomized crossover trial. The participants for this study will be recruited from various places, including the University of Hartford, physical therapy clinics, and local businesses in the Hartford area, as well as online websites geared towards clinical trial recruitment. A total of 34 participants will receive all three treatments: active TENS, placebo TENS, and no treatment control. The treatment order will be randomized using a website-based randomization tool. For active TENS, a modulating frequency of 2-125 Hz will be applied with a variable pulse duration and maximal tolerable intensity for 30 min. The TENS will be left on for post-treatment testing to assess the effects during its maximally effective period for a total of 50 to 60 min. Furthermore, the intensity may be turned down if muscle twitching is present to ensure blinding of the evaluator. For placebo TENS, the unit will deliver current for 45 s, ramping to 0 in the last 15 s. The primary outcome will be pain intensity at rest and with movement, determined using the numerical pain rating scale. The secondary outcomes will be pressure pain threshold, heat pain threshold, temporal summation of pain, conditioned pain modulation, sit-to-stand test, and repeated trunk flexion. The assessments will be performed immediately before and after treatment. Statistical analysis of the data obtained will consider a significance level of p < 0.05.
CONCLUSIONS: This study will provide evidence concerning the effects and mechanisms of TENS treatment in participants with chronic non-specific low back pain. The outcomes, including pain, function, and descending inhibition, will help us gain a greater understanding of how TENS can be used for these participants.
BACKGROUND: ClinicalTrials.gov NCT05812885. Registered on 24th May 2023.

UNASSIGNED: The efficacy and safety of opioid-free anaesthesia during bariatric surgery remain debated, particularly when administering multimodal analgesia. As multimodal analgesia has become the standard of care in many centres, we aimed to determine if such a strategy coupled with either dexmedetomidine (opioid-free anaesthesia) or remifentanil with a morphine transition (opioid-based anaesthesia), would reduce postoperative morphine requirements and opioid-related adverse events.
UNASSIGNED: In this prospective double-blind study, 172 class III obese patients having laparoscopic gastric bypass surgery were randomly allocated to receive either sevoflurane-dexmedetomidine anaesthesia with a continuous infusion of lidocaine and ketamine (opioid-free group) or sevoflurane-remifentanil anaesthesia with a morphine transition (opioid-based group). Both groups received at anaesthesia induction a bolus of magnesium, lidocaine, ketamine, paracetamol, diclofenac, and dexamethasone. The primary outcome was 24-h postoperative morphine consumption. Secondary outcomes included postoperative quality of recovery (QoR40), incidence of hypoxaemia, bradycardia, and postoperative nausea and vomiting (PONV).
UNASSIGNED: Eighty-six patients were recruited in each group (predominantly women, 70% had obstructive sleep apnoea). There was no significant difference in postoperative morphine consumption (median [inter-quartile range]: 16 [13-26] vs 15 [10-24] mg, P=0.183). The QoR40 up to postoperative day 30 did not differ between groups, but PONV was less frequent in the opioid-free group (37% vs 59%, P=0.005). Hypoxaemia and bradycardia were not different between groups.
UNASSIGNED: During bariatric surgery, a multimodal opioid-free anaesthesia technique did not decrease postoperative morphine consumption when compared with a multimodal opioid-based strategy. Quality of recovery did not differ between groups although the incidence of PONV was less in the opioid-free group.
UNASSIGNED: NCT05004519.

Background and Objectives: The analgesia/nociception index (ANI) potentially monitors nociceptive status during anesthesia, but its link to preoperative pain sensitivity is unclear. We investigated the relationship between pre-anesthetic ANI scores and propofol injection pain (PIP) in patients receiving remifentanil. Materials and Methods: This study included 124 male patients aged 19-60 undergoing general anesthesia (ASA class I or II). Patients were randomized to group R (n = 62, remifentanil 4 ng/mL) or group C (n = 62, saline). The primary outcome was the association between PIP and ANI. Secondary outcomes included the incidence and severity of PIP or rocuronium-induced withdrawal movement (RIWM) and their association with ANI. Results: PIP and RIWM incidence and severity were lower in group R than in group C. A weak negative correlation between PIP and ANI at pre-induction (rpb = -0.21, p = 0.02, rpb = -0.37, p < 0.01) and a moderate negative correlation during propofol injection (rpb = -0.48, p = 0.02) were observed. A significant negative correlation was found between RIWM and ANI during rocuronium injection (τb = -0.61, p < 0.01). AUC, cut-off value, specificity, and sensitivity in ANI at pre-induction for predicting PIP were 0.67 (p = 0.02), 59, 76%, and 55%, respectively. AUC, cut-off value, specificity, and sensitivity in ANI during propofol injection for PIP were 0.77 (p < 0.01), 65, 81%, and 67%, respectively. Conclusions: ANI scores demonstrated significant differences between groups, suggesting potential predictive value for PIP despite the low pre-induction AUC value. This study highlights the potential of using ANI scores to predict and manage PIP in patients receiving remifentanil.

Pain is one of the key non-motor symptoms experienced by a large proportion of people living with Parkinson\'s disease (PD), yet the mechanisms behind this pain remain elusive and as such its treatment remains suboptimal. It is hoped that through the study of animal models of PD, we can start to unravel some of the contributory mechanisms, and perhaps identify models that prove useful as test beds for assessing the efficacy of potential new analgesics. However, just how far along this journey are we right now? Is it even possible to model pain in PD in animal models of the disease? And have we gathered any insight into pain mechanisms from the use of animal models of PD so far? In this chapter we intend to address these questions and in particular highlight the findings generated by others, and our own group, following studies in a range of rodent models of PD.

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