Review of enhanced recovery programs in benign gynecologic surgery.

INTRODUCTION AND HYPOTHESIS: Enhanced recovery programs (ERPs) are evidence-based protocols designed to improve functional rehabilitation after surgery. ERPs have gained widespread acceptance in many surgical disciplines, and their use leads to significant improvements in patient outcomes while reducing hospital length of stay (LOS). There remains a paucity of data on the use of ERPs in benign gynecologic surgery. The purpose of this review was to evaluate current literature on the use of ERP concepts in benign gynecologic surgery. METHODS: A systematic search of PubMed, CINAHL, Web of Science, and the Cochrane databases was conducted, cross-referencing search terms related to gynecologic surgery and ERP concepts. The search was limited to publications available in English. Studies published prior to 2000, and those involving gynecologic oncology, nonadult patients, and outpatient surgery were excluded. RESULTS: Nine studies were included in the analysis. Due to heterogeneity of the included studies, no statistical pooling was possible and comparison between studies was limited to their respective themes. Primary study outcomes included LOS, postoperative nausea and vomiting (PONV), pain management, patient satisfaction, and hospital costs. Five studies investigated ERPs, two evaluated measures to improve PONV, and four focused on unique aspects of pain management. Across the studies, ERPs that focused on the patients' basic symptoms and recovery were found to have equal, if not better, outcomes than standard practice. CONCLUSIONS: This integrative review supports the implementation of ERPs in benign gynecologic surgery. The results showed that the use of ERPs decreased LOS, improved pain scores, and reduced hospital costs, without increasing perioperative complications. We suggest additional randomized controlled trials of ERP concepts in benign gynecologic surgery to support their more widespread use and application.

The mixed-action delta/mu opioid agonist MMP-2200 does not produce conditioned place preference but does maintain drug self-administration in rats, and induces in vitro markers of tolerance and dependence.

Previous work in our laboratories provides preclinical evidence that mixed-action delta/mu receptor glycopeptides have equivalent efficacy for treating pain with reduced side effect profiles compared to widely used mu agonist analgesics such as morphine. This study evaluated the rewarding and reinforcing effects of a lead candidate, mixed-action delta/mu agonist MMP-2200, using a conditioned place preference assay as well as a drug self-administration procedure in rats. In place conditioning studies, rats underwent a 2-week conditioning protocol and were then tested for chamber preference. Rats receiving MMP-2200, at previously determined analgesic doses, could not distinguish between the drug and saline-paired chamber, whereas rats receiving the opioid agonist morphine showed a strong preference for the morphine-paired chamber. In self-administration studies, rats were trained to respond for the high efficacy mu opioid receptor agonist fentanyl on an FR5 schedule of reinforcement. Following complete dose-response determinations for fentanyl, a range of doses of MMP-2200 as well as morphine were tested. Relative to the mu agonist morphine, MMP-2200 maintained a significantly lower number of drug infusions. To begin investigating potential molecular mechanisms for the reduced side effect profile of MMP-2200, we also examined ßarrestin2 (ßarr2) recruitment and chronic MMP-2200 induced cAMP tolerance and super-activation at the human delta and mu receptors in vitro. MMP-2200 efficaciously recruited ßarr2 to both receptors, and induced cAMP tolerance and super-activation equivalent to or greater than morphine at both receptors. The in vivo findings suggest that MMP-2200 may be less reinforcing than morphine but may have some abuse potential. The reduced side effect profile cannot be explained by reduced ßarr2 recruitment or reduced cAMP tolerance and superactivation at the monomeric receptors in vitro.

Monosodium iodoacetate-induced osteoarthritis produces pain-depressed wheel running in rats: implications for preclinical behavioral assessment of chronic pain.

Pain stimulates some behaviors (e.g., withdrawal responses) and depresses other behaviors (e.g., feeding and locomotion). We are developing methods for testing candidate analgesics using measurements of pain-depressed behaviors. Such assays may model important aspects of clinical pain and complement traditional procedures that measure pain-stimulated behaviors. The present study characterized the effects of a chronic pain manipulation (monosodium iodoacetate (MIA)-induced osteoarthritis) on wheel running in rats. Rats had 24 h voluntary access to running wheels. Duration of running wheel acquisition was manipulated such that rats had either 21 or 7 days of running wheel access prior to MIA administration. Wheel running was monitored for an additional 21 days following MIA administration. MIA produced concentration- and acquisition length-dependent decreases in wheel running. Parallel experiments demonstrated that MIA produced concentration-dependent tactile allodynia and shifts in hind limb weight bearing. MIA was differentially potent across assays with a potency rank: weight-bearing≥von Frey>running wheel. MIA produced greater depression of wheel running in rats with relatively high baseline running rates compared to rats with relatively low baseline running rates. The differential potency of MIA across assays and apparent rate-dependent effects in running wheels may impact our traditional interpretations of preclinical nociceptive and antinociceptive testing.

Targeting pain-depressed behaviors in preclinical assays of pain and analgesia: drug effects on acetic acid-depressed locomotor activity in ICR mice.

AIMS: Pain depresses expression of many behaviors, and one goal of analgesic treatment is to restore pain-depressed behaviors. Assays that focus on pain-depressed behaviors may contribute to preclinical assessment of candidate analgesics. MAIN METHODS: This study compared effects of the mu opioid receptor agonist morphine (an acknowledged analgesic), the dopamine receptor antagonist haloperidol (a non-analgesic sedative), the adenosine receptor antagonist caffeine (a non-analgesic stimulant) and the neurokinin-1 receptor antagonist CJ 11,974-01 (a candidate analgesic) on acetic acid-induced writhing (a traditional pain-stimulated behavior) and acetic acid-induced suppression of locomotor activity (a pain-depressed behavior) in male ICR mice. Drug effects on non-depressed (baseline) locomotor activity were also examined. KEY FINDINGS: I.P. administration of acetic acid (0.18-1%) was equipotent in stimulating writhing and depressing locomotor activity. Morphine blocked both acid-induced stimulation of writhing and depression of locomotion, although it was 56-fold less potent in the assay of acid-depressed locomotion. Haloperidol and CJ 11,974-01 decreased acid-stimulated writhing, but failed to block acid-induced depression of locomotion. Caffeine had no effect on acid-stimulated writhing or acid-depressed locomotor activity, although it did increase non-depressed locomotion. Thus, morphine was the only drug to block both acid-stimulated writhing and acid-depressed locomotion. SIGNIFICANCE: Complementary assays of pain-stimulated and pain-depressed behaviors may improve the predictive validity of preclinical studies that assess candidate analgesic drugs. The low potency of morphine to block acid-induced depression of locomotion suggests that locomotor activity may be a relatively insensitive measure for studies of pain-depressed behavior.

A guide to cancer pain management.

Most, if not all, cancer patients require care from community teams at some stage during their disease trajectory. For many of these patients, community nurses and General Practitioners are the main point of contact. Pain is reported by between 55-95% of patients with advanced or terminal disease. Optimal pain control positively impacts on the physical, emotional and functional well-being of the patient. Despite the existence of guidelines (WHO, 1996) (SIGN, 2000) and a wealth of literature on cancer pain management, half of all patients in Western countries still do not receive adequate pain relief. This article looks at the reasons behind this and provides community nurses with an overview of up-to-date information on pain pathophysiology and management, so that the control of cancer pain can be optimized in the community.