The arousal level of consciousness required for working memory performance: An anaesthesia study.

Regarding the stage of arousal level required for working memory to function properly, limited studies have been conducted on changes in working memory performance when the arousal level of consciousness decreases. This study aimed to experimentally clarify the stages of consciousness necessary for optimal working memory function. In this experiment, the sedation levels were changed step-by-step using anaesthesia, and the performance accuracy during the execution of working memory was assessed using a dual-task paradigm. Participants were required to categorize and remember words in a specific target category. Categorization performance was measured across four different sedative phases: before anaesthesia (baseline), and deep, moderate and light stages of sedation. Short-delay recognition tasks were performed under these four sedative stages, followed by long-delay recognition tasks after participants recovered from sedation. The results of the short-delay recognition task showed that the performance was lowest at the deep stage. The performance of the moderate stage was lower than the baseline. In the long-delay recognition task, the performance under moderate sedation was lower than that under baseline and light sedation. In addition, the performance under light sedation was lower than that under baseline. These results suggest that task performance becomes difficult under half sedation and that transferring information to long-term memory is difficult even under one-quarter sedation.

Copeptin is associated with microalbuminuria and renal function in the general Japanese population.

An association between copeptin (precursor molecule of arginine vasopressin) and markers for renal function has been reported, but data on the Japanese population has been limited. In this study, we investigated whether elevated copeptin levels are associated with microalbuminuria and renal dysfunction in the general Japanese population. A total of 1,262 participants (842 female and 420 male) were enrolled. Multiple regression analysis was performed to assess the association of copeptin levels (logarithm) with estimated glomerular filtration rate (eGFR) and the urine albumin-to-creatinine ratio (UACR) after adjusting for age, BMI, and lifestyle variables. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression methods in which chronic kidney disease (CKD) was the dependent variable. The copeptin levels differed significantly with sex, but were not found to be related to age or the span of time from preceding meal to blood sampling. In female participants, copeptin level was negatively correlated with eGFR (beta = -0.100, p-value = 0.006) and positively correlated with UACR (beta = 0.099, p-value = 0.003). In male participants, a negative correlation (beta = -0.140, p-value = 0.008) was observed for eGFR. In both females and males, those with high copeptin levels had more than double the ORs of CKD (OR = 2.1-2.9) adjusted for CKD-related factors. The present study found elevated copeptin levels to be associated with renal function loss in the Japanese population and microalbuminuria in female. Moreover, it was evident that high copeptin levels are associated with CKD. These results suggest that copeptin could be considered a marker of renal function.

Ubiquitin specific peptidase 32 acts as an oncogene in epithelial ovarian cancer by deubiquitylating farnesyl-diphosphate farnesyltransferase 1.

Epithelial ovarian cancer (EOC) is the seventh most common cancer worldwide and the deadliest gynecological malignancy because of its aggressiveness and high recurrence rate. To discover new therapeutic targets for EOC, we combined public EOC microarray datasets with our previous in vivo shRNA screening dataset. The top-ranked gene ubiquitin specific peptidase 32 (USP32), coding a deubiquitinating enzyme, is a component of the ubiquitin proteasome system. Clinically, USP32 is expressed in primary ovarian cancer, especially in metastatic peritoneal tumors, and negatively impacts the survival outcome. USP32 regulates proliferative and epithelial mesenchymal transition capacities that are associated with EOC progression. Proteomic analysis identified farnesyl-diphosphate farnesyltransferase 1 (FDFT1) as a novel substrate of USP32 that is an enzyme in the mevalonate pathway, essentially associated with cell proliferation and stemness. USP32 and FDFT1 expression was higher in tumor spheres than in adherent cells. Inhibition of USP32, FDFT1, or mevalonate pathway considerably suppressed tumor sphere formation, which was restored by adding squalene, a downstream product of FDFT1. These findings suggested that USP32-FDFT1 axis contributes to EOC progression, and could be novel therapeutic targets for EOC treatment.

The Relationships Between Pain-Catastrophizing Subcomponents and Multiple Pain-Related Outcomes in Japanese Outpatients with Chronic Pain: A Cross-Sectional Study.

OBJECTIVES: The present study sought to examine associations between the pain-catastrophizing subcomponents and multiple pain-related outcomes in Japanese individuals with chronic pain. METHODS: A cross-sectional study design was employed with 213 chronic pain outpatients. The participants were recruited from 3 units at a university hospital and from a pain clinic at a municipal hospital. Study measures were used to assess pain catastrophizing, anxiety, depression, pain interference, and pain severity. RESULTS: Path analysis with multiple pain-related outcomes while controlling for age and gender revealed that the Helplessness subcomponent was associated with anxiety, depression, pain interference, and pain severity. The Magnification subcomponent was related to anxiety and depression, and the Rumination subcomponent accounted for the variance of pain interference. DISCUSSION: The present results suggested the important role of helplessness across cultural backgrounds. It also provides guidance on the application of cognitive behavioral techniques for chronic pain management in Japan.

Go-sha-jinki-Gan (GJG) ameliorates allodynia in chronic constriction injury-model mice via suppression of TNF-α expression in the spinal cord.

BACKGROUND: Alternative medicine is noted for its clinical effect and minimal invasiveness in the treatment of neuropathic pain. Go-sha-jinki-Gan, a traditional Japanese herbal medicine, has been used for meralgia and numbness in elderly patients. However, the exact mechanism of GJG is unclear. This study aimed to investigate the molecular mechanism of the analgesic effect of GJG in a chronic constriction injury model. RESULTS: GJG significantly reduced allodynia and hyperalgesia from the early phase (von Frey test, p<0.0001; cold-plate test, p<0.0001; hot-plate test p»0.011; two-way repeated measures ANOVA). Immunohistochemistry and Western blot analysis revealed that GJG decreased the expression of Iba1 and tumor necrosis factor-a in the spinal cord. Double staining immunohistochemistry showed that most of the tumor necrosis factor-a was co-expressed in Iba1-positive cells at day 3 post-operation. GJG decreased the phosphorylation of p38 in the ipsilateral dorsal horn. Moreover, intrathecal injection of tumor necrosis factor-a opposed the anti-allodynic effect of GJG in the cold-plate test. CONCLUSIONS: Our data suggest that GJG ameliorates allodynia in chronic constriction injury model mice via suppression of tumor necrosis factor-a expression derived from activated microglia. GJG is a promising drug for the treatment of neuropathic pain induced by neuro-inflammation.

Sensory cognitive abnormalities of pain in autism spectrum disorder: a case-control study.

BACKGROUND: The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) recently included sensory processing abnormalities in the diagnostic criteria for individuals with autism spectrum disorder (ASD). However, there is no standard method for evaluating sensory abnormalities in individuals with ASD. METHODS: Fifteen individuals with ASD and 15 age- and sex-matched controls were enrolled in this study. We compared objective pain sensitivity by measuring the pain detection threshold and pain tolerance to three different stimuli (electricity, heat, and cold). Then, we compared both subjective pain sensitivity, assessed by the visual analog scale (VAS), and quality of pain, assessed by the short-form McGill Pain Questionnaire (SF-MPQ), to determine the maximum tolerable pain intensities of each stimulation. RESULTS: The pain detection threshold and pain tolerance of individuals with ASD were not impaired, indicating that there were no differences in the somatic perception of pain between groups. However, individuals with ASD were hyposensitive to subjective pain intensity compared to controls (VAS; electrical: p = 0.044, cold: p = 0.011, heat: p = 0.042) and hyposensitive to affective aspects of pain sensitivity (SF-MPQ; electrical: p = 0.0071, cold: p = 0.042). CONCLUSIONS: Our results suggest that the cognitive pathways for pain processing are impaired in ASD and, furthermore, that our methodology can be used to assess pain sensitivity in individuals with ASD. Further investigations into sensory abnormalities in individuals with ASD are needed to clarify the pathophysiologic processes that may alter sensory processing in this disorder.

Validation of the Japanese version of the pain self-efficacy questionnaire in Japanese patients with chronic pain.

OBJECTIVES: The present study aimed to develop the Japanese version of the Pain Self-Efficacy Questionnaire (PSEQ-J) and to evaluate its psychometric properties. DESIGN: Cross-sectional design. SETTING: A pain clinic, a neurosurgery unit, and an orthopedic surgery unit in one university hospital and a pain clinic in a municipal hospital. METHODS: One hundred and seventy-six participants completed study measures, which included 1) the PSEQ-J, 2) the Hospital Anxiety and Depression Scale, 3) the Pain Catastrophizing Scale, 4) the Medical Outcome Study Short-Form 36, 5) the Pain Disability Assessment Scale, and 6) the Short-Form McGill Pain Questionnaire. RESULTS: The PSEQ-J demonstrated adequate reliability and validity. Hierarchical multiple regression analyses showed that pain self-efficacy as measured with the PSEQ-J accounted for a significant proportion of the variance on the measures administered in the present study. The PSEQ-J was most strongly associated with social activity. CONCLUSIONS: The results demonstrated that the PSEQ-J has adequate psychometric properties, supporting its use in clinical and research settings and suggest that the PSEQ-J may be particularly strongly associated with more social and less physical activity.

Validity, reliability, and assessment sensitivity of the Japanese version of the short-form McGill pain questionnaire 2 in Japanese patients with neuropathic and non-neuropathic pain.

OBJECTIVE: The objective of this study was to define the validity, reliability, and assessment sensitivity of the Japanese version of the Short-Form McGill Pain Questionnaire 2 (SF-MPQ-2-J). DESIGN: This is a cross-sectional study. PATIENTS AND METHODS: The original SF-MPQ-2 was translated into Japanese to create the SF-MPQ-2-J, and the cross-cultural equivalence of assessment tool for Japanese patients was validated. The reliability of the SF-MPQ-2-J was assessed using internal consistency, reliability coefficients (Cronbach's α), and reproducibility coefficients (intraclass correlation coefficient) obtained using 234 patients with chronic pain. SF-MPQ-2-J validity was assessed based on associations identified between total and subscale scores compared with other assessment methods. A confirmatory factor analysis (CFA) was also performed to test the theoretical structure of the SF-MPQ-2-J. RESULTS: The internal consistencies calculated included continuous pain, α=0.893; intermittent pain, α=0.875; predominantly neuropathic pain, α=0.917; affective descriptors, α=0.857; and total score, α=0.907. The reproducibility coefficients calculated included continuous pain, ρ=0.81; intermittent pain, ρ=0.78; predominantly neuropathic pain, ρ=0.85; affective descriptors, ρ=0.75; and total score, ρ=0.83. The CFA showed that the model fit of the readily interpretable subscales was acceptable, and the goodness of fit index value was 0.917. In addition, the mean predominantly neuropathic pain subscale score was found to be significantly higher for patients with neuropathic pain vs non-neuropathic pain. CONCLUSION: These findings suggest that the reliability and validity of the SF-MPQ-2-J are excellent, and the SF-MPQ-2-J represents a cross-cultural equivalent to SF-MPQ-2. Consequently, the latter is suitable for research and clinical use, and for discriminating neuropathic pain from non-neuropathic pain.

Non-invasive differentiation of hepatic steatosis and steatohepatitis in a mouse model using nitroxyl radical as an MRI-contrast agent.

Drug-induced steatohepatitis is considered more serious than drug-induced hepatic steatosis, so that differentiating between the two is crucial in drug development. In addition, early detection of drug-induced steatohepatitis is considered important since recovery is possible with drug withdrawal. However, no method has been established to differentiate between the two. In the development of drug-induced steatohepatitis, reactive oxygen species (ROS) is excessively generated in the liver. It has been reported that ROS can be monitored with electron spin resonance (ESR) and dynamic nuclear polarization-magnetic resonance imaging (DNP-MRI) by using nitroxyl radicals, which are known to participate in various in vivo redox reactions. The decay/reduction rate, which is an index for monitoring nitroxyl radicals, has been reported to be increased in tissues with excessive ROS levels other than liver, but decreased in methionine choline deficient (MCD) diet-induced steatohepatitis with excess ROS. Therefore, looking to differentiate between drug-induced hepatic steatosis and steatohepatitis, we examined whether the reduction rate decreases in steatohepatitis other than the MCD-diet induced disease and whether the decrease could be detected by MRI. We used STAM™ mice in which hepatic steatosis and steatohepatitis developed sequentially under diabetic conditions. 3-carbamoyl-PROXYL (CmP), one of the nitroxyl radicals, was injected intravenously during the MRI procedure and the reduction rate was calculated. The reduction rate was significantly higher in early steatohepatitis than in hepatic steatosis and the control. Excess ROS in early steatohepatitis was detected by an immunohistochemical marker for ROS. Therefore, it was indicated that the increase or decrease in the reduction rate in steatohepatitis differs depending on the model, and early steatohepatitis could be noninvasively differentiated from hepatic steatosis using CmP in MRI. Since the change in direction of the reduction rate in steatohepatitis in clinical studies could be predicted by confirming the reduction rate in preclinical studies, the present method, which can be used consistently in clinical and preclinical studies, warrants consideration as a candidate monitoring method for differentiating between early drug-induced steatohepatitis and hepatic steatosis in drug development.

Evaluation of in vivo MRI for detecting midodrine-induced arteritis in rats.

There are no specific and sensitive biomarkers for arteritis, and the occurrence of arteritis in nonclinical toxicological studies of a candidate drug makes development of the drug very difficult. However, we showed in a previous study that the high signal intensity region around the artery on magnetic resonance imaging (MRI) could be a candidate biomarker for detection of arteritis. The present study was conducted to clarify the details of midodrine hydrochloride (MH)-induced arteritis lesions and whether arteritis induced by a mechanism other than the vasodilatory effect, which was evaluated in a previous study, could be detected by MRI. MH is a selective peripherally acting alpha-1 adrenergic receptor agonist, known to induce arteritis due to its vasoconstrictor action, but there is not enough information about MH-induced arteritis. Based on the data obtained under multiple dosing conditions, MH was administered subcutaneously to each rat once daily for 2 days at a dose level of 40 mg/kg/day for MRI assessment. The mesenteric arteries were examined using in vivo MRI at 1 day or 7 days after administration of the final dose and examined histopathologically. On the day after the final dose, high signal intensity region around the artery was observed in animals with minimal perivascular lesions confirmed by histopathology and not observed in an animal without histological changes. On the 7th day after the final dose, no abnormality was observed in histopathological examinations and no high signal intensity regions were observed by MRI in any animal. In conclusion, although further investigation is needed to confirm that high signal intensity is a reliable biomarker for humans, it is suggested that high signal intensity around the artery could be a versatile candidate biomarker with high specificity and sensitivity.

Comparison of 1H-magnetic resonance spectroscopy and blood biochemistry as methods for monitoring non-diffuse hepatic steatosis in a rat model.

No method of monitoring drug-induced hepatic steatosis has been established, which is a concern in drug development. Hepatic steatosis is divided into diffuse and non-diffuse forms according to the pattern of fat deposition. Diffuse hepatic steatosis was reported as evaluable by 1H-magnetic resonance spectroscopy (1H-MRS), which is used as an adjunct to the MRI examination. Blood biomarkers for hepatic steatosis have been also actively investigated. However, there are few reports to conduct 1H-MRS or blood test in human or animal non-diffuse hepatic steatosis with reference to histopathology. Therefore, to investigate whether non-diffuse hepatic steatosis can be monitored by 1H-MRS and/or blood samples, we compared histopathology to 1H-MRS and blood biochemistry in a non-diffuse hepatic steatosis rat model. Non-diffuse hepatic steatosis was induced by feeding rats the methionine choline deficient diet (MCDD) for 15 days. The evaluation sites of 1H-MRS and histopathological examination were three hepatic lobes in each animal. The hepatic fat fraction (HFF) and the hepatic fat area ratio (HFAR) were calculated from 1H-MRS spectra and digital histopathological images, respectively. Blood biochemistry analyses included triglycerides, total cholesterol, alanine aminotransferase, and aspartate aminotransferase. A strong correlation was found between HFFs and HFARs in each hepatic lobe (r = 0.78, p < 0.0001) in rats fed the MCDD. On the other hand, no correlation was found between blood biochemistry values and HFARs. This study showed that 1H-MRS parameters correlated with histopathological changes but blood biochemistry parameters didn't, so that it is suggested that 1H-MRS has the potential to be a monitoring method for non-diffuse hepatic steatosis in rats fed the MCDD. Given that 1H-MRS is commonly used in preclinical and clinical studies, 1H-MRS should be considered a candidate method for monitoring drug-induced hepatic steatosis.

Benefits of Laparoscopic Surgery for Bleeding Events in Patients with Implantable Left Ventricular Assist Devices during Antithrombotic Therapy.

Hemorrhagic ovarian cysts (HOCs), a common gynecological disease causing intraabdominal bleeding, can be life threatening in patients undergoing antithrombotic therapy, especially those with left ventricular assist device (LVAD) implantation under strong antithrombotic therapy. We encountered three postLVAD implantation cases with intraabdominal bleeding due to suspected HOCs, which required surgery for hemostasis. Such patients are not only at a higher risk of bleeding but also have restrictions in available surgical incision sites to avoid damaging the LVAD driveline located underneath the abdominal wall. Laparoscopic surgery, which can be performed through minute incisions with flexible site selection, may benefit intraabdominal hemorrhage patients with LVADs.

Detection of fenoldopam-induced arteritis in rats using ex vivo / in vivo MRI.

A method capable of identifying drug-induced arteritis is highly desirable because no specific and sensitive biomarkers have yet been defined. Although magnetic resonance imaging (MRI) may be used to find a biomarker candidate for drug-induced arteritis, there are no reports on the evaluation of drug-induced arteritis by MRI. The present study was conducted to clarify whether Fenoldopam mesylate (FM)-induced arteritis in rats can be detected by MRI. FM, a dopamine (D1 receptor) agonist, is known to induce arteritis in rats. FM was administered subcutaneously to each rat once daily for 2 days at a dose of 100 mg/kg/day. These arteries were examined with ex vivo high-resolution MRI or postmortem MRI after euthanasia. These arteries were also examined using in vivo MRI on the day after final dosing or 3 days after administration of the final dose. These arteries were examined histopathologically in all experiments. The ex vivo MRI showed low-intensity areas and a high signal intensity region around the artery, and these findings were considered to be erythrocytes infiltrating the arterial wall and perivascular edema, respectively. In the in vivo study, the MRI of the FM-administered group showed a high signal intensity region around the artery. The perivascular edema observed histopathologically was recognized as a high signal intensity region around the artery on the image of MRI. In conclusion, detection of the high signal intensity region around the artery by MRI is considered to be a useful method for identifying arteritis. Although further investigation is needed to be a reliable biomarker, it is suggested that it could be a biomarker candidate.

The animal model of spinal cord injury as an experimental pain model.

Pain, which remains largely unsolved, is one of the most crucial problems for spinal cord injury patients. Due to sensory problems, as well as motor dysfunctions, spinal cord injury research has proven to be complex and difficult. Furthermore, many types of pain are associated with spinal cord injury, such as neuropathic, visceral, and musculoskeletal pain. Many animal models of spinal cord injury exist to emulate clinical situations, which could help to determine common mechanisms of pathology. However, results can be easily misunderstood and falsely interpreted. Therefore, it is important to fully understand the symptoms of human spinal cord injury, as well as the various spinal cord injury models and the possible pathologies. The present paper summarizes results from animal models of spinal cord injury, as well as the most effective use of these models.

Sleeping Beauty Transposon Mutagenesis Identifies Genes Driving the Initiation and Metastasis of Uterine Leiomyosarcoma.

Uterine leiomyosarcoma (ULMS) is a malignancy, which arises from the uterine smooth muscle. Because of its rarity, aggressive nature, and extremely poor prognosis, the molecular mechanisms driving ULMS remain elusive. To identify candidate cancer genes (CCG) driving ULMS, we conducted an in vivo Sleeping Beauty (SB) transposon mutagenesis screen in uterine myometrium-specific, PTEN knockout, KRAS mutant (PTEN KO/KRAS) mice. ULMS quickly developed in SB PTEN KO/KRAS mice, but not in PTEN KO/KRAS mice, demonstrating the critical importance of SB mutagenesis for driving ULMS in this model. Subsequent sequencing of SB insertion sites in these tumors identified 19 ULMS CCGs that were significantly enriched in known cancer genes. Among them, Zfp217 and Sfmbt2 functioned at early stages of tumor initiation and appeared to be oncogenes. Expression of ZNF217, the human homolog of ZFP217, was shown to be elevated in human ULMS compared with paired normal uterine smooth muscle, where it negatively correlated with patient prognosis. Inhibition of ZNF217 suppressed, whereas overexpression induced, proliferation, survival, migration, and stemness of human ULMS. In a second ex vivo ULMS SB metastasis screen, three CCGs were identified that may drive ULMS metastasis to the lung. One of these CCGs, Nrd1 (NRDC in humans), showed stronger expression in human metastatic tumors compared with primary ULMS and negatively associated with patient survival. NRDC knockdown impaired migration and adhesion without affecting cell proliferation, whereas overexpression had the opposite effect. Together, these results reveal novel mechanism driving ULMS tumorigenesis and metastasis and identify ZNF217 and NRDC as potential targets for ULMS therapy. SIGNIFICANCE: An in vivo Sleeping Beauty transposon mutagenesis screen identifies candidate cancer genes that drive initiation and progression of uterine leiomyosarcoma and may serve as therapeutic targets.

Pregnancy does not enhance volatile anesthetic sensitivity on the brain: an electroencephalographic analysis study.

BACKGROUNDS: Parturients are thought to be more sensitive to inhalational anesthetics because their minimum alveolar concentration is decreased. However, this conventional theory may be wrong, because, according to recent animal studies, minimum alveolar concentration indicates anesthetic effect on the spinal cord but not on the brain. The aim of this electroencephalographic study was to investigate the differences in the hypnotic effect of sevoflurane on parturients and nonpregnant patients. METHODS: Fifteen parturients undergoing cesarean section and 15 patients undergoing elective gynecologic surgery were enrolled. Anesthesia was induced with 4 mg/kg thiopental, 2 microg/kg fentanyl, and 2 mg/kg suxamethonium or 0.15 mg/kg vecuronium. Anesthesia was maintained with sevoflurane and fentanyl. The electroencephalographic signals, obtained from the bispectral index monitor, were recorded on a computer. We calculated 95% spectral edge frequency, amplitude, and bicoherence using custom software (Bispectrum Analyzer for bispectral index). After confirming that end-tidal sevoflurane had reached equilibrium, we measured electroencephalographic parameters of sevoflurane at 2.0 and 1.5% during surgery and at 1.0 and 0.5% after surgery. RESULTS: With the decrease of end-tidal sevoflurane concentration from 2.0 to 0.5%, 95% spectral edge frequency, amplitude, bispectral index, and bicoherence values changed dose-dependently in pregnant and nonpregnant women (P<0.0001). However, there were no significant differences in those electroencephalographic parameters in pregnant and nonpregnant women. CONCLUSIONS: This electroencephalographic study has shown that pregnancy does not enhance hypnotic effect of sevoflurane. These results suggested that the decrease in minimum alveolar concentration during pregnancy does not mean an enhanced volatile anesthetic effect on the brain.

Corrigendum: An Evolutionarily Threat-Relevant Odor Strengthens Human Fear Memory.

[This corrects the article DOI: 10.3389/fnins.2020.00255.].

An Evolutionarily Threat-Relevant Odor Strengthens Human Fear Memory.

Olfaction is an evolutionary ancient sense, but it remains unclear to what extent it can influence routine human behavior. We examined whether a threat-relevant predator odor (2-methyl-2-thiazoline) would contextually enhance the formation of human fear memory associations. Participants who learned to associate visual stimuli with electric shock in this predator odor context later showed stronger fear responses to the visual stimuli than participants who learned in an aversiveness-matched control odor context. This effect generalized to testing in another odor context, even after extinction training. Results of a separate experiment indicate that a possible biological mechanism for this effect may be increased cortisol levels in a predator odor context. These results suggest that innate olfactory processes can play an important role in human fear learning. Modulatory influences of odor contexts may partly explain the sometimes maladaptive persistence of human fear memory, e.g., in post-traumatic stress disorders.

The role of RNA editing of the serotonin 2C receptor in a rat model of oro-facial neuropathic pain.

We examined whether infraorbital nerve injury affected the RNA editing efficiency of the serotonin (5HT) 2C receptor in the cervical spinal cord, in association with increased pain thresholds, and whether a 5HT reuptake inhibitor (fluvoxamine; Depromel, Meiji Seika, Tokyo, Japan) altered this editing. Accordingly, we injured rats with an infraorbital nerve loose ligation and examined the pain thresholds, mRNA and mRNA editing of the 5HT2C receptor. We evaluated changes in mRNA editing and 5HT2C mRNA expression using cloning along with sequence analysis and quantitative reverse transcription-polymerase chain reaction to compare samples taken at post-injury day 28 from spinal cord sites, including the trigeminal nucleus caudalis, in naive, sham and injured rats (groups of each type had also received fluvoxamine). 5HT2C receptor expression was maintained post-injury. The RNA editing efficiency was statistically significantly lower at molecular sites A and B in ipsilateral spinal cord samples from injured rats than in bilateral samples from naive and sham rats, and in contralateral samples from injured rats. After injury, the proportional presence of two receptor isoforms changed, i.e. statistically significantly less VNV and significantly more INV and ISV. The proportions reverted after fluvoxamine administration. The post-injury change might be evidence of a functional adaptation mechanism that increases the expression of 5HT2C mRNA isoforms that encode receptors that are more sensitive to 5HT. This would activate the brainstem-spinal descending 5HT systems and, in effect, suppress nociceptive signals from primary afferent neurons to the spinal trigeminal nucleus caudalis.

Serotonin2C receptor mRNA editing in neuropathic pain model.

We investigated the effects on 5HT(serotonin) 2C receptor RNA editing efficiency of contusive SCI (spinal cord injury). Using cloning followed by sequence analysis on spinal cord samples taken, we compared mRNA editing. Our results might be evidence of a functional adaptation mechanism in which increased expression of 5HT2C mRNA isoforms that encode receptors more sensitive to serotonin works to activate brainstem-spinal descending 5HT systems to, in effect, suppress transmission of nociceptive signals from primary afferent neurons to the spinal dorsal horn.