1.
Systematic Review and Meta-Analysis of Genetic Risk of Developing Chronic Postsurgical Pain.
Chidambaran, V, Gang, Y, Pilipenko, V, Ashton, M, Ding, L
The journal of pain. 2020;(1-2):2-24
Abstract
Chronic postsurgical pain (CPSP) is a significant detriment to postsurgical recovery and a risk factor for prolonged opioid use. Emerging evidence suggests the estimated heritability for chronic pain is 45% and that genetic factors partially explain individual susceptibility to CPSP. The aim of this study was to systematically review, assess quality, and summarize the studies in humans that have investigated genetic factors associated with CPSP. We also conducted a meta-analysis to derive a single effect size for evaluable genetic associations with CPSP. Our comprehensive literature search included review of 21 full-text articles evaluating variants of 69 genes for association with CPSP. We found significant gene variant associations reported for variants/haplotypes of 26 genes involved in neurotransmission, pain signaling, immune responses and neuroactive ligand-receptor interaction, with CPSP. Six variants of 5 genes (COMT: rs4680 and rs6269, OPRM1: rs1799971, GCH1: rs3783641, KCNS1: rs734784 and TNFA rs1800629), were evaluated by more than one study and were included in the meta-analysis. At rs734784 (A>G) of KCNS1, presence of G allele marginally increased risk of CPSP (Additive genetic model; Odds ratio: 1.511; 95% CI 1-2.284; P value: .050), while the other variants did not withstand meta-analyses criteria. Our findings demonstrate the role of genetic factors with different functions in CPSP, and also emphasize that single genetic factors have small effect sizes in explaining complex conditions like CPSP. Heterogeneity in surgical cohorts, population structure, and outcome definitions, as well as small number of available studies evaluating same variants, limit the meta-analysis. There is a need for large-scale, homogenous, replication studies to validate candidate genes, and understand the underlying biological networks underpinning CPSP. PERSPECTIVE Our systematic review comprehensively describes 21 studies evaluating genetic association with CPSP, and limitations thereof. A meta-analysis of 6 variants (5 genes) found marginally increased risk for CPSP associated with rs734784 A>G of the potassium voltage-gated channel gene (KCNS1). Understanding genetic predisposition for CPSP will enable prediction and personalized management.
2.
Effects of Postoperative Pain Management on Immune Function After Laparoscopic Resection of Colorectal Cancer: A Randomized Study.
Kim, SY, Kim, NK, Baik, SH, Min, BS, Hur, H, Lee, J, Noh, HY, Lee, JH, Koo, BN
Medicine. 2016;(19):e3602
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Abstract
There has been a rising interest in the possible association between perioperative opioid use and postoperative outcomes in cancer patients. Continuous surgical wound infiltration with local anesthetics is a nonopioid analgesic technique that can be used as a postoperative pain management alternative to opioid-based intravenous patient-controlled analgesia (IV PCA). The aim of this study was to compare the effects of an opioid-based analgesic regimen versus a local anesthetic wound infiltration-based analgesic regimen on immune modulation and short-term cancer recurrence or metastasis in patients undergoing laparoscopic resection of colorectal cancer.Sixty patients undergoing laparoscopic resection of colorectal cancer were randomly assigned to either the opioid group or the ON-Q group. For postoperative analgesia during the first 48 hours, the opioid group (n = 30) received fentanyl via IV PCA, whereas the ON-Q group (n = 30) received continuous wound infiltration of 0.5% ropivacaine with an ON-Q pump and tramadol via IV PCA. Pethidine for the opioid group and ketorolac or propacetamol for the ON-Q group were used as rescue analgesics. Anesthesia was induced and maintained with propofol and remifentanil. The primary outcome was postoperative immune function assessed by natural killer cell cytotoxicity (NKCC) and interleukin-2. Secondary outcomes were postoperative complications, cancer recurrence, or metastasis within 1 year after surgery, and postoperative inflammatory responses measured by white blood cell count, neutrophil percentage, and C-reactive protein. Immune function and inflammatory responses were measured before surgery and 24 and 48 hours after surgery.Fifty-nine patients completed the study. In the circumstance of similar pain control efficacy between the opioid group and the ON-Q group, postoperative NKCC and interleukin-2 levels did not differ between the 2 groups. The incidence of postoperative complications and recurrence or metastasis within 1 year after surgery was comparable between the groups. Postoperative inflammatory responses were also similar between the groups.When compared with ropivacaine wound infiltration-based analgesia, fentanyl-based analgesia did not further decrease NKCC or affect short-term cancer recurrence or metastasis. Thus, a fentanyl-based analgesic regimen and a ropivacaine wound infiltration-based analgesic regimen can both be used for postoperative pain management in laparoscopic resection of colorectal cancer.
3.
Intrathecal morphine suppresses NK cell activity following abdominal surgery.
Yokota, T, Uehara, K, Nomoto, Y
Canadian journal of anaesthesia = Journal canadien d'anesthesie. 2000;(4):303-8
Abstract
PURPOSE The effects of morphine on natural killer (NK) cell activity were investigated in patients who underwent hysterectomy. METHODS Forty patients were divided into four groups of ten. The groups received intrathecal 0.5 mg morphine (Group IT0.5), intrathecal 0.1 mg morphine (Group IT0.1) or 10 mg morphine i.v. (Group IV). The remaining ten patients served as controls and received inhalation anesthesia alone (Group C). Blood samples were withdrawn before and two hours after surgery and on postoperative days one and two to determine the blood NK cell activity using a chromium release assay with K562 cells as targets, plasma catecholamines and cortisol levels. The postoperative pain score and side effects were studied in the four groups. RESULTS In Group IT0.5, the NK cell activity was lower on postoperative day 1 (23.9 +/- 8.4%) than the baseline level (45.7 +/- 13%) before surgery, and recovered on postoperative day 2. In Groups IT0.1, C and IV, the NK cell activities showed no significant changes. In all four groups, neither plasma adrenaline nor noradrenaline concentrations changed. In all four groups, the plasma cortisol levels increased after surgery, on postoperative days 1 and 2. The pain score was lower two hours after surgery and on postoperative day 1 in Group IT0.5 than in the other groups. CONCLUSION These results suggest that long-lasting analgesic effects of intrathecal 0.5 mg morphine suppress the immune response following abdominal surgery.