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Xiu Ling Jacqueline Sim,1 Chin Wen Tan,2,3 Cheng Teng Yeam,4 Hon Sen Tan,2,3 Rehena Sultana,5 Ban Leong Sng2,3 1Department of Anesthesiology, Singapore General Hospital, Singapore, Singapore; 2Department of Women’s Anesthesia, KK Women’s and Children’s Hospital, Singapore, Singapore; 3Anesthesiology and Perioperative Sciences Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore; 4MOH Holdings, Singapore, Singapore; 5Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore, SingaporeCorrespondence: Ban Leong Sng Tel +65 6394 1081Fax +65 6291 2661Email sng.ban.leong@singhealth.com.sgBackground: Labor pain is a variable and complex experience with both sensory and affective components. Pain catastrophizing tendencies are predictive of increased distress during labor. Likewise, pain severity has important associations with increased depressive symptoms in mothers, with consequences on perinatal and infant outcomes. Hence, we investigated the association between increased early labor pain with both pre-delivery pain catastrophizing and depressive states.Methods: We recruited nulliparous women who had requested labor epidural analgesia. Pre-delivery questionnaires including short-form McGill pain questionnaire– 2 (SF-MPQ-2), pain catastrophizing scale (PCS), and Edinburgh postnatal depression score (EPDS) were administered.Results: A total of 712 women completed the pre-delivery questionnaires. There was a significant association between SF-MPQ-2 neuropathic subscale and EPDS ≥ 10 (unadjusted OR 1.74, 95% CI 1.11– 2.73, p = 0.0161), as well as PCS ≥ 25 (unadjusted OR 1.55, 95% CI 1.06– 2.26, p = 0.0244). SF-MPQ-2 sensory intermittent subscale and EPDS ≥ 10 (unadjusted OR 2.02, 95% CI 1.34– 3.03, p = 0.0007), and PCS ≥ 25 (unadjusted OR 1.59, 95% CI 1.14– 2.23, p = 0.0069) also showed significant association.Conclusion: Increased sensory intermittent and neuropathic subsets of early labor pain are significantly correlated with increased pre-delivery pain catastrophizing and depressive states in nulliparous women. This positive association may be useful for pre-delivery risk stratification for early interventions towards a more holistic care management.Keywords: labor pain, pain catastrophizing, pre-delivery depression, survey

Hon Sen Tan,1 Ashraf S Habib2 1Department of Women’s Anesthesia, KK Women’s and Children’s Hospital, 229899, Singapore; 2Department of Anesthesiology, Division of Women’s Anesthesia, Duke University Medical Center, Durham, NC, 27710, USACorrespondence: Ashraf S HabibDepartment of Anesthesiology, Division of Women’s Anesthesia, Duke University Medical Center, Box 3094, Durham, NC, 27710, USATel +1 9196682024Email ashraf.habib@duke.eduAbstract: Optimal pain relief requires a balance between adequate analgesia and risk of adverse effects. Opioids remain the cornerstone for managing moderate to severe pain, but are associated with opioid-induced respiratory depression (OIRD) and gastrointestinal complications. Opioids exert their analgesic effects predominantly via G-protein signaling, however, adverse effects including OIRD are mediated by the β-arrestin pathway. Oliceridine is the first of a new class of biased opioid agonists that preferentially activate G-protein signaling over β-arrestin, which would theoretically improve analgesia and reduce the risk of adverse effects. Oliceridine is approved by the Food and Drug Administration (FDA) for the treatment of moderate to severe acute pain. The efficacy of Oliceridine was mainly established in two randomized controlled Phase III clinical trials of patients experiencing moderate to severe pain after bunionectomy (APOLLO-1) and abdominoplasty (APOLLO-2). The results of the APOLLO studies demonstrate that Oliceridine, when administered via patient-controlled analgesia (PCA) demand boluses of 0.35mg and 0.5mg, provides superior analgesia compared to placebo, and is equianalgesic to PCA morphine 1mg demand boluses, without significant difference in the incidence of respiratory complications. In a more pragmatic trial of surgical and non-surgical patients, the ATHENA observational cohort study reported rapid onset of analgesia with Oliceridine given with or without multimodal analgesia. However, these studies were designed to evaluate analgesic efficacy, and it is still uncertain if Oliceridine has a better safety profile than conventional opioids. Although several post hoc analyses of pooled data from the APOLLO and ATHENA trials reported that Oliceridine was associated with lower OIRD and gastrointestinal complications compared to morphine, prospective studies are needed to elucidate if biased agonists such as Oliceridine reduce the risk of adverse effects compared to conventional opioids.Keywords: TRV130, biased ligand, opioid agonist, mu-opioid receptor

Hon Sen Tan,1 Rehena Sultana,2 Nian-Lin Reena Han,3 Chin Wen Tan,1,4 Alex Tiong Heng Sia,1,4 Ban Leong Sng1,4 1Department of Women’s Anaesthesia, KK Women’s and Children’s Hospital, Singapore; 2Centre for Quantitative Medicine, Duke-NUS Medical School, Singapore; 3Division of Clinical Support Services, KK Women’s and Children’s Hospital, Singapore; 4Anesthesiology and Perioperative Sciences Academic Clinical Program, SingHealth-Duke-NUS Medical School, SingaporeCorrespondence: Ban Leong SngDepartment of Women’s Anaesthesia, KK Women’s and Children’s Hospital, 100 Bukit Timah Road 229899, SingaporeTel +65 6394 1077Email sng.ban.leong@singhealth.com.sgPurpose: Hysterectomy is associated with a high incidence of chronic post-hysterectomy pain (CPHP). Pain catastrophizing, a negative cognitive-affective response to pain, is associated with various pain disorders but its role in CPHP is unclear. We aimed to determine the association of high preoperative pain catastrophizing with CPHP development and functional impairment 4 months after surgery.Patients and Methods: Secondary analysis of a prospective cohort study of women undergoing abdominal/laparoscopic hysterectomy to investigate the association between high pain catastrophizing (pain catastrophizing scale, PCS≥ 20) with CPHP and associated functional impairment (defined as impairment with standing for ≥ 30 minutes, sitting for ≥ 30 minutes, or walking up or down stairs). CPHP and functional impairment were assessed via 4- and 6-month phone surveys.Results: Of 216 patients, 72 (33.3%) had high PCS, with mean (SD) of 30.0 (7.9). In contrast, 144 (66.7%) patients had low PCS, with mean (SD) of 9.0 (4.7). At 4 months, 26/63 (41.3%) patients in the high PCS group developed CPHP, compared to 24/109 (22.0%) in the low PCS group. At 6 months, 14/53 (26.4%) high PCS patients developed CPHP, compared to 10/97 (10.3%) patients with low PCS. High PCS was independently associated with CPHP at 4 months (OR 2.49 [95% CI 1.27 to 4.89], p=0.0082) and 6 months (OR 3.12 [95% CI 1.28 to 7.64], p=0.0126) but was not associated with functional impairment. High PCS≥ 20, presence of evoked mechanical temporal summation (MTS), and history of abdominal/pelvic surgery predict CPHP at 4 months with area under the curve (AUC) of 0.69. Similarly, PCS≥ 20 and increasing MTS magnitude predicted CPHP at 6 months with AUC of 0.76.Conclusion: High PCS was independently associated with CPHP. Future studies should identify other CPHP associated factors to formulate a risk-prediction model and investigate the effectiveness of early intervention for pain catastrophizers in improving pain-related outcomes.Keywords: pain catastrophizing scale, mechanical temporal summation