Natural history of postoperative neuropathies in gynecologic surgery.

INTRODUCTION AND HYPOTHESIS: Neuropathy following pelvic surgery is an uncommon but important complication. The current literature about the natural history and treatment of these neuropathies is limited. We aim to describe the characteristics, treatments and natural history of postoperative neuropathy following benign gynecologic surgery. METHODS: This retrospective case series included patients who underwent benign gynecologic surgery for ≥ 60 min in lithotomy. Patients with preexisting neurologic disease were excluded. Patient demographics, identification of postoperative neuropathy and details regarding evaluation and treatment were obtained from the medical record. Neuropathies were characterized by anatomic location and nerve/dermatome distribution. Duration of symptoms was classified as < 1 week, 1 week to 3 months or > 3 months with neuropathy symptoms grouped as resolved, persistent but improved or persistent. Data were analyzed with appropriate descriptive statistics, Pearson correlation and chi-square test. RESULTS: The study included 2449 patients who had undergone benign gynecologic surgery, with 78 (3.2%) patients identified as having postoperative neuropathy. Most patients with neuropathies demonstrated either complete resolution [59 (75.6%)] or persistent but improved [13 (16.7%)] symptoms. Twenty-eight (35.9%) had symptoms of ≥ 3 months. Most neuropathies were sensory only [63 (80.8%)], and the most frequently documented nerve distribution was femoral [23 (29.5%)]. Evaluation and treatment of neuropathy most commonly included physical therapy consult [17 (21.8%)] and neurology consult [8 (10.3%)]. CONCLUSIONS: The incidence of postoperative neuropathy in this large, benign gynecologic surgery population was 3.2%. Most neuropathies are sensory only and self-limited. While physical therapy was the most common treatment, most patients received no specific intervention.

Differential Expression Patterns of Lynx Proteins and Involvement of Lynx1 in Prepulse Inhibition.

Negative allosteric modulators, such as lynx1 and lynx2, directly interact with nicotinic acetylcholine receptors (nAChRs). The nAChRs are integral to cholinergic signaling in the brain and have been shown to mediate different aspects of cognitive function. Given the interaction between lynx proteins and these receptors, we examined whether these endogenous negative allosteric modulators are involved in cognitive behaviors associated with cholinergic function. We found both cell-specific and overlapping expression patterns of lynx1 and lynx2 mRNA in brain regions associated with cognition, learning, memory, and sensorimotor processing, including the prefrontal cortex (PFC), cingulate cortex, septum, hippocampus, amygdala, striatum, and pontine nuclei. Since lynx proteins are thought to play a role in conditioned associations and given the expression patterns across brain regions, we first assessed whether lynx knockout mice would differ in a cognitive flexibility task. We found no deficits in reversal learning in either the lynx1-/- or lynx2-/- knockout mice. Thereafter, sensorimotor gating was examined with the prepulse inhibition (PPI) assessment. Interestingly, we found that both male and female lynx1-/- mice exhibited a deficit in the PPI behavioral response. Given the comparable expression of lynx2 in regions involved in sensorimotor gating, we then examined whether removal of the lynx2 protein would lead to similar behavioral effects. Unexpectedly, we found that while male lynx2-/- mice exhibited a decrease in the baseline startle response, no differences were found in sensorimotor gating for either male or female lynx2-/- mice. Taken together, these studies provide insight into the expression patterns of lynx1 and lynx2 across multiple brain regions and illustrate the modulatory effects of the lynx1 protein in sensorimotor gating.

Postoperative Lower Extremity Neuropathy With Boot Stirrups Compared With Candy Cane Stirrups.

OBJECTIVE: To assess whether candy cane stirrup use is associated with an increased risk of lower extremity peripheral neuropathy compared with boot stirrups in women undergoing surgery requiring dorsal lithotomy positioning. METHODS: This retrospective cohort study (June 2008-August 2015) included patients who underwent gynecologic surgery for benign indication lasting 60 minutes or longer in the lithotomy position. Patients with preexisting neurologic disease were excluded. Stirrup type, demographics, medical history, surgical factors, and relevant outcomes were collected from the medical record. Postoperative neuropathy was identified in clinical diagnoses or in physician documentation through the 6-week postoperative visit. Patient characteristics and outcomes were compared using Student's t test, χ2 test, or Fisher exact test. Logistic regression analysis was used to adjust for other clinical characteristics associated with the outcome at P≤.1. RESULTS: The study included 2,449 patients, 1,838 (75.1%) with boot and 611 (24.9%) with candy cane stirrups. Women positioned in boot stirrups were younger (mean age 45.6 years [SD 13.5] vs 55.9 [SD 15.7] years; P<.001), heavier (mean body mass index [BMI] 31.5 [SD 8.7] vs 29.6 [SD 7.0]; P<.001), more likely to smoke (n=396 [21.5%] vs n=105 [17.2%]; P=.021), and had longer surgical duration (mean 176.5 minutes [SD 90.0] vs 145.3 [SD 63.9] minutes; P<.001), respectively. Diabetes (8.3%) did not differ between the groups (P=.122. Neuropathy occurred less often in the boot cohort (n=29, 1.6%, 95% CI 1.1-2.3%) than in the candy cane cohort (n=21, 3.4%, 95% CI 2.1-5.2%) (P=.008). After adjusting for age, BMI, smoking, anesthesia type and surgical time, only candy cane stirrup type (adjusted odds ratio [aOR] 2.87, 95% CI 1.59-5.19) and surgical time (per hour) (aOR 1.40, 95% CI 1.20-1.63) were independently associated with postoperative neuropathy. CONCLUSION: Candy cane stirrups are associated with a significantly increased risk of lower extremity postoperative neuropathy compared with boot stirrups for women undergoing gynecologic surgery for benign indication.

The Interpeduncular-Ventral Hippocampus Pathway Mediates Active Stress Coping and Natural Reward.

Maladaptive stress-related behaviors are integral to multiple complex psychiatric disorders, and it has been well established that serotonergic signaling mediates various aspects of these maladaptive states. In these studies, we sought to uncover the function of a previously undefined serotonergic pathway, which projects from the interpeduncular nucleus (IPN) to the ventral hippocampus (vHipp). Intersectional retrograde and chemogenetic viral manipulation strategies were employed to manipulate the function of the IPN-vHipp pathway during a variety of behavioral measures in male mice. We found a significant effect of circuit inhibition on behaviors associated with coping strategies and natural reward. Specifically, inhibition of the IPN-vHipp pathway dramatically increased active stress-induced escape behaviors, in addition to moderately affecting sucrose consumption and food self-administration. During inhibition of this pathway, agonist activation of serotonergic 5-HT2A/2C receptors in the vHipp reversed the effects of IPN-vHipp circuit inhibition on active escape behaviors, thereby supporting the synaptic mechanism underlying the behavioral effects evidenced. IPN-vHipp inhibition did not induce differences in generalized locomotion, anxiety-associated behavior, and intravenous nicotine self-administration. Importantly, these findings are in opposition to the canonical understanding of serotonin in such escape behaviors, indicating that serotonin exerts opposing effects on behavior in a pathway-specific manner in the brain. Taken together, these findings thereby have important implications for our understanding of serotonergic signaling and associated therapeutic approaches for the treatment of disease symptomology.

Cannabinoid and nicotine exposure during adolescence induces sex-specific effects on anxiety- and reward-related behaviors during adulthood.

Nicotine and cannabis use during adolescence has the potential to induce long lasting changes on affective and cognitive function. Here, we examined whether adolescent exposure to nicotine, the cannabinoid agonist WIN55-212,2 (WIN), or co-exposure to both would alter operant learning, locomotion, and anxiety- and reward-related behaviors in male and female mice during adulthood. Males exposed to a moderate dose of WIN (2 mg/kg) or co-exposed to nicotine and the moderate dose of WIN exhibited decreased anxiety-associated behaviors and increased cognitive flexibility, but did not differ in operant learning or generalized locomotion. In contrast, differences were not found among the females in these measures at the moderate WIN dose or in both sexes with exposure to a low WIN dose (0.2 mg/kg). Furthermore, a sex-dependent dissociative effect was found in natural reward consumption. Males exposed to the moderate dose of WIN or co-exposed to nicotine and the moderate dose of WIN demonstrated increased sucrose consumption. In contrast, females exposed to the moderate dose of WIN exhibited a decrease in sucrose consumption, which was ameliorated with co-administration of nicotine. Together, these novel findings demonstrate that adolescent exposure to cannabinoids in the presence or absence of nicotine results in altered affective and reward-related behaviors during adulthood.

Altered Baseline and Nicotine-Mediated Behavioral and Cholinergic Profiles in ChAT-Cre Mouse Lines.

The recent development of transgenic rodent lines expressing cre recombinase in a cell-specific manner, along with advances in engineered viral vectors, has permitted in-depth investigations into circuit function. However, emerging evidence has begun to suggest that genetic modifications may introduce unexpected caveats. In the current studies, we sought to extensively characterize male and female mice from both the ChAT(BAC)-Cre mouse line, created with the bacterial artificial chromosome (BAC) method, and ChAT(IRES)-Cre mouse line, generated with the internal ribosome entry site (IRES) method. ChAT(BAC)-Cre transgenic and wild-type mice did not differ in general locomotor behavior, anxiety measures, drug-induced cataplexy, nicotine-mediated hypolocomotion, or operant food training. However, ChAT(BAC)-Cre transgenic mice did exhibit significant deficits in intravenous nicotine self-administration, which paralleled an increase in vesicular acetylcholine transporter and choline acetyltransferase (ChAT) hippocampal expression. For the ChAT(IRES)-Cre line, transgenic mice exhibited deficits in baseline locomotor, nicotine-mediated hypolocomotion, and operant food training compared with wild-type and hemizygous littermates. No differences among ChAT(IRES)-Cre wild-type, hemizygous, and transgenic littermates were found in anxiety measures, drug-induced cataplexy, and nicotine self-administration. Given that increased cre expression was present in the ChAT(IRES)-Cre transgenic mice, as well as a decrease in ChAT expression in the hippocampus, altered neuronal function may underlie behavioral phenotypes. In contrast, ChAT(IRES)-Cre hemizygous mice were more similar to wild-type mice in both protein expression and the majority of behavioral assessments. As such, interpretation of data derived from ChAT-Cre rodents must consider potential limitations dependent on the line and/or genotype used in research investigations.SIGNIFICANCE STATEMENT Altered baseline and/or nicotine-mediated behavioral profiles were discovered in transgenic mice from the ChAT(BAC)-Cre and ChAT(IRES)-Cre lines. Given that these cre-expressing mice have become increasingly used by the scientific community, either independently with chemicogenetic and optogenetic viral vectors or crossed with other transgenic lines, the current studies highlight important considerations for the interpretation of data from previous and future experimental investigations. Moreover, the current findings detail the behavioral effects of either increased or decreased baseline cholinergic signaling mechanisms on locomotor, anxiety, learning/memory, and intravenous nicotine self-administration behaviors.