This paper is the forty-fifth consecutive installment of the annual anthological review of research concerning the endogenous opioid system, summarizing articles published during 2022 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides and receptors as well as effects of opioid/opiate agonists and antagonists. The review is subdivided into the following specific topics: molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors (1), the roles of these opioid peptides and receptors in pain and analgesia in animals (2) and humans (3), opioid-sensitive and opioid-insensitive effects of nonopioid analgesics (4), opioid peptide and receptor involvement in tolerance and dependence (5), stress and social status (6), learning and memory (7), eating and drinking (8), drug abuse and alcohol (9), sexual activity and hormones, pregnancy, development and endocrinology (10), mental illness and mood (11), seizures and neurologic disorders (12), electrical-related activity and neurophysiology (13), general activity and locomotion (14), gastrointestinal, renal and hepatic functions (15), cardiovascular responses (16), respiration and thermoregulation (17), and immunological responses (18). 

Endogenous opiates and behavior: 2022

Background: Total hip replacement (THR) is frequently associated with intense post-surgical pain. Effective pain management is of crucial importance to improving patient's condition and increasing his/her satisfaction in the post-operative time. Objectives: This study aimed to compare the analgesic effect and safety of oxycodone and fentanyl after THR. Methods: Seventy-two cases scheduled for elective THR were included in this randomized, triple-blind trial. The patients were equally randomized into 2 groups: fentanyl group (50 ug of fentanyl) and oxycodone group (oxycodone 4 mg). Drugs were received 20 min prior to the end of the operation. Results: Post-operative visual analog scale (VAS) measurements at rest and movement at the post-anesthesia care unit (PACU) and in the ward, 2 h, 4 h, and 8 h post-operatively exhibited a significantly reduced value in the oxycodone group compared to the fentanyl group (P-value < 0.05). Time to first rescue for analgesia was delayed significantly in the oxycodone compared to the fentanyl group (P-value < 0.001). Fentanyl consumption (ug) in the 1st post-operative 12 h, 24 h, and 48 h decreased significantly in the oxycodone group compared to the fentanyl group (P-value < 0.001). Post-operative nausea, vomiting, headache, and pruritus were matched between the 2 groups (P > 0.05). Conclusions: A bolus dose of 4 mg of oxycodone provided superior analgesic efficacy than 50 ug fentanyl as evidenced by significantly lower pain score, delayed onset to first request for analgesia, and the smaller amount of fentanyl consumption at 12, 24, and 48 h post-total hip arthroplasty compared to fentanyl. The incidence of adverse events was comparable between the 2 groups.

Comparison of Effectiveness and Safety of Oxycodone Hydrochloride and Fentanyl for Post-operative Pain Following Total Hip Arthroplasty: A Randomized Triple-Blind Trial

Backgroud To compare how five common opioids affect rat intestinal muscle tension and frequency across concentrations, establishing an animal model to provide translational evidence for selecting opioids with the least gastrointestinal impact. Methods Isolated rat small intestine specimens were prepared, and six intestinal segments were selected from the same rat and placed into remifentanil, sufentanil, oxycodone, nalbuphine, butorphanol, and the control group with balanced solution. Experiments were carried out to observe and compare the changes in the contraction tension and contraction frequency of small intestinal smooth muscle during the change in concentration gradients of 10– 9 , 10– 8 , 10– 7 , 10– 6 , 10– 5 , and 10– 4 M. Statistical analysis obtained from 10 rats in the in vitro intestinal tube experiment was performed. Results The results revealed that when the concentration increased to 10 −7 M, the intestinal contraction tension in the butorphanol group began to decrease significantly, and the intestinal contraction tension in the nalbuphine and oxycodone groups began to decrease significantly at concentrations of 10 −6 M. while the sufentanil group and the remifentanil group showed a significant decrease in intestinal contractile tension at 10 −5 M and 10 −4 M, respectively. When the concentration of the drug increased to 10 −4 M, the contraction frequency of the sufentanil group decreased significantly, and there was no statistical difference among concentrations of other drugs. Conclusion As the concentration increased, different opioids inhibited the contractile tone of rat intestinal smooth muscle in vitro . The intensity of inhibition was butorphanol &amp;gt; nalbuphine ≈ oxycodone &amp;gt; sufentanil &amp;gt; remifentanil, and the Contraction frequency was almost unaffected except in the very high concentration sufentanil group. 

pdf/effects-of-different-opioids-on-the-contractile-tension-of-hojrf3z9vh0q.pdf

Effects of different opioids on the contractile tension of isolated rat intestinal smooth muscle

Perioperative opioid use is associated with postoperative bowel dysfunction, which causes longer hospital stay and higher healthcare costs. This study aimed to investigate the effect of the equivalent doses of fentanyl, oxycodone, and butorphanol on bowel function in patients undergoing laparoscopic hysterectomy.In this randomized controlled trial, 135 patients undergoing laparoscopic hysterectomy received postoperative intravenous patient-controlled analgesia (IV-PCA) with fentanyl 8.3 μg/kg, butorphanol 0.16 mg/kg, and oxycodone 0.5 mg/kg (1: 20: 60), respectively. The primary outcome measure was the recovery of bowel function. We also evaluated and recorded the following nine indicators: pain score, sedation level, leukocyte count, percentage of neutrophils, plasma potassium levels, time to first ambulation, postoperative side effects, patients' satisfaction, and postoperative hospital length of stay.The mean time to flatus was significantly prolonged in Group B (45.2 ± 11.6 h) compared with Group F (33.1 ± 11.2 h, P < 0.001) and Group O (36.2 ± 10.9 h, P = 0.001). The incidence of somnolence and dizziness prove higher in Group B (P < 0.001). No statistical difference was observed in the mean time to tolerate oral diet, time to defecation, analgesic outcome, satisfaction score, time to first ambulation, and postoperative hospital length of stay.Compared with fentanyl and oxycodone, butorphanol prolonged the recovery of bowel function with more severe somnolence and dizziness, suggesting that butorphanol is not well suitable for IV-PCA in patients undergoing laparoscopic hysterectomy.ClinicalTrials.gov- NCT04295109 . Date of registration: March, 2020. 

/pdf/the-effects-of-fentanyl-oxycodone-and-butorphanol-on-l3ma3urc.pdf

The effects of fentanyl, oxycodone, and butorphanol on gastrointestinal function in patients undergoing laparoscopic hysterectomy: a prospective, double-blind, randomized controlled trial

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The effects of fentanyl, oxycodone, and butorphanol on gastrointestinal function in patients undergoing laparoscopic hysterectomy: a prospective, double-blind, randomized controlled trial