The effect of vitamin D and omega-3 fatty acid supplementation on pain prevalence and severity in older adults: a large-scale ancillary study of the VITamin D and OmegA-3 triaL (VITAL).

ABSTRACT: A diet supplemented with vitamin D and marine omega-3 fatty acids may prevent and treat painful disorders by promoting the resolution of inflammation. However, large, randomized placebo-controlled trials evaluating the effects of supplementation with omega-3 fatty acids and vitamin D on the presence and severity of pain are lacking. VITamin D and OmegA-3 triaL-Pain (VITAL-Pain) is an ancillary study to the VITAL trial, a large randomized, double-blind, placebo-controlled trial of vitamin D (2000 IU/day) and omega-3 supplementation (1 g/day) over 5.3 years of median follow-up, among 25,871 older men and women. We assessed pain among those reaching the end of the VITAL intervention phase using questions from the 2012 National Health Interview Survey. We used ordinal logistic regression to test the effect of vitamin D and omega-3 fatty acids on the odds ratio (OR) and 95% confidence interval [CI] of reporting higher pain prevalence or severity. Overall, 19,611 participants provided complete pain information at the end of the VITAL trial. The ORs for higher pain prevalence or severity for vitamin D and omega-3 supplementation vs placebo were 0.99 ([CI] 0.94-1.05) and 0.99 ([CI] 0.94-1.04), respectively. There was no interaction between the 2 active treatments. Dietary supplementation with commonly used moderate doses of vitamin D or omega-3 fatty acids over a median of 5.3 years did not result in a lower prevalence or severity of pain in middle-aged and older U.S. adults.

Perioperative Sleep Disturbance Following Mastectomy: A Longitudinal Investigation of the Relationship to Pain, Opioid Use, Treatment, and Psychosocial Symptoms.

OBJECTIVES: Sleep disturbance negatively impacts the quality of life and recovery. Our objective was to evaluate the relationship between the individual patient and surgical factors with greater sleep disturbance following breast surgery. METHODS: In this prospective longitudinal study, patients completed validated measures regarding sleep disturbance, pain, opioid use, and psychological symptoms preoperatively and then 2 weeks, 6 and 12 months postoperatively. Univariable and multivariable generalized estimating equations evaluated demographic, surgical, pain, and psychological predictors of sleep disturbance during the first year after breast surgery. RESULTS: Female patients (n=259) reported varying degrees of sleep disturbance, which were longitudinally associated with pain and psychosocial factors (eg, anxiety, depression, and affect). Independent preoperative predictors of worse sleep disturbance included younger age (B=-0.09, P =0.006), opioid use (B=3.09, P =0.02), and higher pain (B=0.19, P =<0.001) and anxiety (B=0.45, P =<0.001) at baseline. In addition, higher baseline positive affect (B=-0.14, P =<0.012) and the surgical category total mastectomy without reconstruction (B=-2.81, P =<0.006) were independently associated with lower sleep disturbance. Those with worse baseline sleep required more opioid analgesics during surgical recovery, and continued use of opioids at 2 weeks postsurgery was associated with disturbed sleep. DISCUSSION: Certain patient characteristics, including younger age and baseline anxiety, positive affect, pain, and opioid use, were associated with greater sleep disturbance in the first year after breast surgery. Sleep disturbance was also associated with the greater perioperative and postoperative opioid requirements. Preoperative interventions (eg, anxiety management, cultivating positive affect, and multimodal pain management) in high-risk individuals may enhance sleep and recovery postoperatively, and allow more moderate and less prolonged opioid use.

Less stress, better success: a scoping review on the effects of anxiety on anesthetic and analgesic consumption.

Preoperative anxiety has an incidence of 11-80% in patients undergoing surgical or interventional procedures. Understanding the role of preoperative anxiety on intraoperative anesthetic requirements and postoperative analgesic consumption would allow personalized anesthesia care. Over- or under-anesthetizing patients can lead to complications such as postoperative cognitive dysfunction in elderly patients, or procedural discomfort, respectively. Our scoping review focuses on the current evidence regarding the association between preoperative anxiety and intraoperative anesthetic and/or postoperative analgesic consumption in patients undergoing elective surgical or interventional procedures. Based on 44 studies that met the inclusion criteria, we found that preoperative anxiety has a significant positive correlation effect on intraoperative propofol and postoperative opioid consumption. The analysis of the literature is limited by the heterogeneity of preoperative anxiety tools used, study designs, data analyses, and outcomes. The use of shorter, validated preoperative anxiety assessment tools may help optimize the intraoperative anesthetic and postoperative analgesic regimen. Further research to determine the most feasible and clinically relevant preoperative anxiety tool and subsequent implementation has the potential to optimize perioperative care and improve patient outcomes.

Biosynthetic metabolomes of cysteinyl-containing immunoresolvents.

Resolution of inflammation is an active process regulated by specialized proresolving mediators where we identified 3 new pathways producing allylic epoxide-derived mediators that stimulate regeneration [i.e., peptido-conjugates in tissue regeneration (CTRs)]. Here, using self-limited Escherichia coli peritonitis in mice, we identified endogenous maresin (MaR) CTR (MCTR), protectin (PD) CTR (PCTR), and resolvin CTR in infectious peritoneal exudates and distal spleens, as well as investigated enzymes involved in their biosynthesis. PCTRs were identified to be temporally regulated in peritoneal exudates and spleens. PCTR1 and MCTR1 were each produced by human recombinant leukotriene (LT) C4 synthase (LTC4S) and glutathione S-transferases (GSTs) [microsomal GST (mGST)2, mGST3, and GST-µ (GSTM)4] from their epoxide precursors [16S,17S-epoxy-PD (ePD) and 13S,14S-epoxy-MaR (eMaR)], with preference for GSTM4. Both eMaR and ePD inhibited LTB4 production by LTA4 hydrolase. LTC4S, mGST2, mGST3, and GSTM4 were each expressed in human M1- and M2-like macrophages where LTC4S inhibition increased CTRs. Finally, PCTR1 showed potent analgesic action. These results demonstrate CTR biosynthesis in mouse peritonitis, human spleens, and human macrophages, as well as identification of key enzymes in these pathways. Moreover, targeting LTC4S increases CTR metabolomes, giving a new strategy to stimulate resolution and tissue regeneration.-Jouvene, C. C., Shay, A. E., Soens, M. A., Norris, P. C., Haeggström, J. Z., Serhan, C. N. Biosynthetic metabolomes of cysteinyl-containing immunoresolvents.

Anesthesia considerations and post-operative pain management in pregnant women with chronic opioid use.

The prevalence of opioid use disorder in pregnancy has escalated markedly in recent years. Chronic opioid use during pregnancy poses several challenges for providing adequate analgesia and anesthesia in the peripartum period. These challenges include the potential for withdrawal, opioid tolerance and opioid-induced hyperalgesia. Here we discuss alterations in analgesic pharmacokinetics and pharmacodynamics that are associated with chronic opioid use. In addition, when treating pain in patients with opioid use disorder it is important to distinguish between different subgroups. In this review, we will discuss practical management strategies for parturients with (1) untreated opioid use disorder, (2) parturients on medication-assisted treatment (methadone, buprenorphine) and (3) patients recovering from opioid use disorder that are currently abstinent. Finally, we offer an overview of non-opioid strategies that may be utilized as part of a multimodal approach to providing optimal analgesia in this patient population.

Association of Interindividual Variation in Plasma Oxytocin With Postcesarean Incisional Pain.

Oxytocin has known antinociceptive effects and is upregulated perinatally. This pilot study investigated the association of plasma oxytocin and postcesarean incisional pain. Plasma samples from 18 patients undergoing elective cesarean delivery were drawn at 1 hour preoperatively and 1 and 24 hours postoperatively and analyzed by using enzyme-linked immunosorbent assay. Pain was assessed at 1 day, 8 weeks, 3 months, and 6 months postoperatively. Incisional pain at 24 hours was inversely correlated with 1- and 24-hour oxytocin levels, with higher plasma oxytocin associated with lower pain (ρ, -0.52 and -0.66; P < .05).

A Randomized, Double-blinded Trial of a "Rule of Threes" Algorithm versus Continuous Infusion of Oxytocin during Elective Cesarean Delivery.

BACKGROUND: The administration of uterotonic agents during cesarean delivery is highly variable. The authors hypothesized a "rule of threes" algorithm, featuring oxytocin 3 IU, timed uterine tone evaluations, and a systematic approach to alternative uterotonic agents, would reduce the oxytocin dose required to obtain adequate uterine tone. METHODS: Sixty women undergoing elective cesarean delivery were randomized to receive a low-dose bolus or continuous infusion of oxytocin. To blind participants, the rule group simultaneously received intravenous oxytocin (3 IU/3 ml) and a "wide-open" infusion of 0.9% normal saline (500 ml); the standard care group received intravenous 0.9% normal saline (3 ml) and a "wide-open" infusion of oxytocin (30 IU in 0.9% normal saline/500 ml). Uterine tone was assessed at 3, 6, 9, and 12 min, and if inadequate, additional uterotonic agents were administered. Uterine tone, total dose and timing of uterotonic agent use, maternal hemodynamics, side effects, and blood loss were recorded. RESULTS: Adequate uterine tone was achieved with lower oxytocin doses in the rule versus standard care group (mean, 4.0 vs. 8.4 IU; point estimate of the difference, 4.4 ± 1.0 IU; 95% CI, 2.60 to 6.15; P < 0.0001). No additional oxytocin or alternative uterotonic agents were needed in either group after 6 min. No differences in the uterine tone, maternal hemodynamics, side effects, or blood loss were observed. CONCLUSION: A "rule of threes" algorithm using oxytocin 3 IU results in lower oxytocin doses when compared with continuous-infusion oxytocin in women undergoing elective cesarean delivery.

Prolonged cutaneous analgesia with transdermal application of amitriptyline and capsaicin.

BACKGROUND AND OBJECTIVES: Capsaicin selectively binds to TRPV1, the vanilloid subtype 1 of the superfamily of transient receptor potential ion channels, which is highly expressed in pain-transmitting C fibers. Recent reports have demonstrated that the coadministration of capsaicin with a local anesthetic (LA) at the rat sciatic nerve elicits a prolonged nociceptive-selective nerve block, suggesting that activation of the TRPV1 receptor may allow LAs to enter the nerve through the TRPV1 pore. In previous studies, we demonstrated that transdermal amitriptyline achieves clinical analgesic effects and is more potent than lidocaine. Here we examine whether the combined application of amitriptyline and capsaicin as a transdermal patch will produce prolonged cutaneous analgesia compared with amitriptyline alone. METHODS: Male Sprague-Dawley rats (weights 250-300 g) were assigned to five treatment groups (n = 6-8 per group). Transdermal patches containing amitriptyline with different concentrations of capsaicin were applied for 3 hrs to rats' shaved backs: 2.5% amitriptyline alone (control group) and in combination with 0.05%, 0.15%, 1%, and 8% capsaicin. Behavioral testing for cutaneous nociception was conducted before drug application and after patch removal using the cutaneous trunci muscle reflex. In addition, skin appearance was assessed to determine irritation by these formulations. RESULTS: The cutaneous analgesic effect is significantly prolonged when amitriptyline is applied in combination with 8% capsaicin. Amitriptyline alone provided a complete block to pinprick for 4.5 hrs, and the time to full recovery was 96 hrs. Amitriptyline with 8% capsaicin produced a complete block to pinprick for 6 to 9 hrs, and the time to full recovery was 216 hrs (P = 0.002). Amitriptyline alone causes toxic effects in skin, whereas the higher the concentration of capsaicin, the less skin irritation was noted, and the combination of amitriptyline 2.5% with capsaicin 8% caused no adverse skin reactions. CONCLUSIONS: This study demonstrates that the combined application of amitriptyline and capsaicin results in prolonged cutaneous analgesia compared with amitriptyline alone, suggesting that the activation of the TRPV1 channel by capsaicin facilitates the passage of amitriptyline into nociceptors. This transdermal patch achieves far longer cutaneous analgesia than currently available patch applications such as EMLA cream. The mechanism that underlies the lesser skin irritation noted when amitriptyline is combined with higher doses of capsaicin compared with amitriptyline alone is unclear and may be related to a counteraction of amitriptyline-induced vasoconstriction.

Obstetric anesthesia for the obese and morbidly obese patient: an ounce of prevention is worth more than a pound of treatment.

BACKGROUND: The incidence of obesity has been dramatically increasing across the globe. Anesthesiologists, are increasingly faced with the care for these patients. Obesity in the pregnant woman is associated with a broad spectrum of problems, including dramatically increased risk for cesarean delivery, diabetes, hypertension and pre-eclampsia. A thorough understanding of the physiology, associated conditions and morbidity, available options for anesthesia and possible complications is therefore important for today's anesthesiologist. METHODS: This is a personal review in which different aspects of obesity in the pregnant woman, that are relevant to the anesthesiologist, are discussed. An overview of maternal and fetal morbidity and physiologic changes associated with pregnancy and obesity is provided and different options for labor analgesia, the anesthetic management for cesarean delivery and potential post-partum complications are discussed in detail. RESULTS AND CONCLUSION: The anesthetic management of the morbidly obese parturient is associated with special hazards. The risk for difficult or failed intubation is exceedingly high. The early placement of an epidural or intrathecal catheter may overcome the need for general anesthesia, however, the high initial failure rate necessitates critical block assessment and catheter replacement when indicated.