Humanin's impact on pain markers and neuronal viability in diabetic neuropathy model.

OBJECTIVE: This study investigates the impact of chronic humanin (HN) treatment on pain-related markers (NMDA, substance P, TRPV1, and IL-1ß) in diabetic mice's dorsal root ganglia (DRG). Additionally, we assess the effects of HN on cellular viability in DRG neurons. METHODS: In vivo experiments involved 15 days of HN administration (4 mg/kg) to diabetic mice (n = 10). Protein levels of NMDA, IL-1ß, TRPV1, and substance P were measured in diabetic DRG. In vitro experiments explored HN's impact on apoptosis and cellular viability, focusing on the JAK2/STAT3 pathway. RESULTS: Humanin significantly reduced the elevated expression of NMDA, IL-1ß, TRPV1, and substance P induced by diabetes (p < .05). Furthermore, HN treatment increased cellular viability in DRG neurons through JAK2/STAT3 pathway activation (p < .05). CONCLUSION: These findings highlight the significance of understanding mitochondrial function and pain markers, as well as apoptosis in diabetes. The study provides insights for managing the condition and its complications.

Elevated Asprosin Levels in Breast Cancer: Insights from a Comparative Study.

Background: Breast cancer (BC) is the most common type of cancer in women. Diagnosis in the early stage is very important for cancer treatment. There is no good biomarker to diagnose BC in T1-T2 or N0 stage. This study aimed to evaluate asprosin (ASP) levels of BC compared with non-cancer. Materials and Methods: An enzyme-linked immunosorbent assay was used to evaluate serum ASP levels in 40 patients with BC and 40 healthy women. The cancer group included T1-T4, N1-N3, and M0-M1 patients. T stages were divided into groups as T1-T2 and T3-T4. N stages were divided into groups as N (0) and N (+). Results: ASP showed good discrimination (area under the curve = 0.767, 95% confidence interval: 0.657-0.878) between the BC group and the healthy group and acceptable discriminating ability (sensitivity = 0.825; specificity = 0.750) at the optimal cutoff value of 1.82 ng/mL. ASP indicated no difference for T, N, and M stages (p = 0.919, p = 0.859, and p = 0.225, respectively). There was a significant difference between grades within cancer patients in terms of ASP (p = 0.025). Conclusions: These findings provide evidence of a potential association between elevated ASP levels and the presence of BC. The observed higher levels of ASP in women with BC compared with healthy individuals suggest that ASP could potentially serve as a biomarker for distinguishing between the two groups. These results may contribute to our understanding of the potential role of ASP in BC detection and highlight its potential as a diagnostic marker. Further studies are required to establish whether ASP can be used to diagnose BC.

Modulation of Neuronal Damage in DRG by Asprosin in a High-Glucose Environment and Its Impact on miRNA181-a Expression in Diabetic DRG.

Asprosin, a hormone secreted from adipose tissue, has been implicated in the modulation of cell viability. Current studies suggest that neurological impairments are increased in individuals with obesity-linked diabetes, likely due to the presence of excess adipose tissue, but the precise molecular mechanism behind this association remains poorly understood. In this study, our hypothesis that asprosin has the potential to mitigate neuronal damage in a high glucose (HG) environment while also regulating the expression of microRNA (miRNA)-181a, which is involved in critical biological processes such as cellular survival, apoptosis, and autophagy. To investigate this, dorsal root ganglion (DRG) neurons were exposed to asprosin in a HG (45 mmol/L) environment for 24 hours, with a focus on the role of the protein kinase A (PKA) pathway. Expression of miRNA-181a was measured by using real-time polymerase chain reaction (RT-PCR) in diabetic DRG. Our findings revealed a decline in cell viability and an upregulation of apoptosis under HG conditions. However, pretreatment with asprosin in sensory neurons effectively improved cell viability and reduced apoptosis by activating the PKA pathway. Furthermore, we observed that asprosin modulated the expression of miRNA-181a in diabetic DRG. Our study demonstrates that asprosin has the potential to protect DRG neurons from HG-induced damage while influencing miRNA-181a expression in diabetic DRG. These findings provide valuable insights for the development of clinical interventions targeting neurotoxicity in diabetes, with asprosin emerging as a promising therapeutic target for managing neurological complications in affected individuals.

Exploring the potential of humanin as a biomarker for early breast cancer detection: a study of serum levels and diagnostic performance.

INTRODUCTION: Breast cancer is a leading cause of cancer death in women worldwide, and early detection is crucial for effective treatment. Mitochondrial dysfunction has been linked to cancer development and progression. Humanin, a mitochondrial-derived peptide, has been shown to have cytoprotective effects and may be involved in breast cancer development. In this study, we aimed to investigate the potential of humanin as a biomarker for breast cancer. METHODS: We recruited 45 female patients diagnosed with primary invasive ductal breast cancer and 45 healthy volunteers. Serum humanin levels were measured using ELISA, and other cancer markers were measured using an Advia Centaur Immunology Analyser. RESULTS: Our results showed that serum humanin levels were significantly higher in breast cancer patients than in healthy controls (p = 0.008). ROC curve analysis indicated that humanin could effectively discriminate between patients and healthy individuals, with a sensitivity of 62.5% and a specificity of 77.5%. CONCLUSION: This suggests that humanin may be a potential new biomarker for breast cancer screening and early detection. Further research is needed to fully understand the relationship between humanin and breast cancer and to develop new diagnostic and therapeutic strategies.

Protective effects of chronic humanin treatment in mice with diabetic encephalopathy: A focus on oxidative stress, inflammation, and apoptosis.

Diabetes is known to cause cognitive impairments through various mechanisms, including oxidative stress, inflammation, and apoptosis. Humanin (HN) has been shown to have protective effects on cognitive impairments induced by factors such as Aß, muscarinic receptor antagonists, and aging in rodents. However, the mechanisms underlying the protective effects of HN in the prefrontal cortex and hippocampus in the context of diabetes are not well understood. In this study, we aimed to investigate the potential protective role of HN on oxidative stress, inflammation, and apoptosis in mice with diabetes. We divided the mice into four groups, including a control group (treated with saline), a humanin group (treated with 4 mg/kg of HN), a streptozotocin (STZ) group (diabetic control), and an STZ+Humanin group. The mice were administered HN daily for 15 days. Our results showed that in the prefrontal cortex and hippocampus of the diabetes group, oxidative stress parameters, pro-inflammatory cytokines, apoptosis and, blood glucose levels were increased, while antioxidant and anti-inflammatory cytokines were diminished compared to the control group. However, HN treatment was able to modulate these markers, including blood glucose and the markers of oxidative stress, inflammation, and apoptosis. In conclusion, our findings suggest that hyperglycemia, oxidative stress, inflammation, and apoptosis may contribute to the development of diabetes-induced cognitive impairments. By regulating these changes with HN treatment, we may be able to positively contribute to the treatment of cognitive impairments induced by diabetes.

Asprosin, a novel therapeutic candidate for painful neuropathy: an experimental study in mice.

Recent studies indicate presence of a strong link between adipokines and neuropathic pain. However, the effects of asprosin, a novel adipokine, on neuropathic pain have not been studied in animal models.Mouse models were employed to investigate the antinociceptive effectiveness of asprosin in the treatment of three types of neuropathic pain, with metabolic (streptozocin/STZ), toxic (oxaliplatin/OXA), and traumatic (sciatic nerve ligation/CCI [chronic constriction nerve injury]) etiologies, respectively. Changes in nociceptive behaviors were assessed relative to controls using thermal (the hot plate and cold plate tests, at 50 °C and 4 °C respectively) and mechanical pain (von Frey test) tests after intraperitoneal (i.p.) administration of asprosin (10 µg/kg) and gabapentin (50 mg/kg) in several times intervals. Besides, possible effect of asprosin on the motor coordination of mice was assessed with a rotarod test. Serum level of asprosin was quantified by ELISA.In neuropathic pain models (STZ, OXA, and CCI), asprosin administration significantly reduced both mechanical and thermal hypersensitivity, indicating that it exhibits a clear-cut antihypersensitivity effect in the analyzed neuropathic pain models. The most effective time of asprosin on pain threshold was observed 60 min after its injection. Also, asprosin displayed no notable effect on the motor activity. Asprosin levels were significantly lower in neuropathic pain compared to healthy group (p < 0.05).The results yielded by the present study suggest that asprosin exhibits an analgesic effect in the neuropathic pain models and may have clinical utility in alleviating chronic pain associated with disease and injury originating from peripheral structures.

The modulatory effects of irisin on asprosin, leptin, glucose levels and lipid profile in healthy and obese male and female rats.

OBJECTIVES: The main aim of this study was to investigate the effects of irisin on asprosin, leptin, glucose levels and lipid profile in healthy and obese male and female rats. METHODS: Irisin was subcutaneously administered with osmotic minipumps at the dose of 100 ng/kg/day for 28 days and then, the serum levels of asprosin, leptin, glucose and lipid profile were investigated. RESULTS: Irisin infusion increased asprosin levels in male rats (p = .02) but not in female rats. Irisin inhibited obesity-induced high glucose, low-density lipoprotein (LDL), triglyceride (TG) and leptin levels in all groups; however, it did not lead to any change in asprosin levels in both obese female and male rats. CONCLUSIONS: It was determined that irisin increased serum asprosin levels and decreased LDL, TG, glucose and leptin levels, and this could indicate a protective role of irisin against obesity development.

The Long-Term Effects of Plasma Disc Coagulation Therapy for Cervical Disc Hernia.

OBJECTIVES: Recently, plasma disc coagulation therapy (PDCT) has been used in the treatment of lumbar and cervical disc hernia (CDH), but the long-term effects of PDCT have not been well documented. The aim of this study was to assess the long-term effects of PDCT on pain score, disc volume and patient satisfaction in patients with CDH. METHODS: Eighty patients with CDH, who underwent PDCT treatment, were included in the study. The patients demographics and pain scores (visual analog scale-VAS) were recorded on the baseline and in the 1st, 3rd, 6th and 12th month after PDCT treatment. We evaluated patient satisfaction and disc volume on the 12th month after PDCT. RESULTS: A statistically significant and time-dependent decrease was determined in VAS score. The initial mean VAS score was 6.5 ± 0.9, and it decreased to 3.4 ± 0.2 on the final follow-up (p<0.01). According to magnetic resonance imaging pathology, VAS score after PDCT was higher in patients with an extruded disc when compared to patients with bulging and protruded discs at all times (p<0.05). After 12 months, 50 % of the patients were reported as excellent and 8.7 % of the patients reported as poor based on the Odoms' criteria. Disc volume decreased after PDCT treatment in the patients who reported that they were excellent based on the Odoms' criteria (p<0.01). CONCLUSIONS: This study demonstrated that PDCT is a safe, effective and minimally invasive treatment technique for adequately selected patients with CDH.

Evaluation of the Effect of Erector Spinae Plane Block in Patients Undergoing Belt Lipectomy Surgery.

BACKGROUND: The interest in and demand for post-bariatric surgery have increased along with the increase in obesity surgery. Belt lipectomy, during which a circular correction is made in the center of the trunk, is the most commonly performed among these surgical techniques. Postoperative pain is an important problem due to the size of the surgical site and stretched closure. In this study, it was aimed to evaluate the intraoperative and postoperative narcotic analgesic consumption, postoperative analgesic requirement, postoperative visual analog scale (VAS) scores, postoperative nausea and vomiting (PONV), and the first mobilization time in patients with and without erector spinae plane block (ESPB). METHODS: The files of patients who had undergone belt lipectomy between 2016 and 2019 in our hospital were retrospectively reviewed. Patients who received ESPB were called group 1, and those who did not undergo ESPB were called group 2. Their demographic characteristics, intraoperative and postoperative narcotic and non-narcotic analgesic consumption, VAS scores, PONV, and the first mobilization times were recorded. RESULTS: The files of a total of 51 patients, including 23 patients in group 1 and 28 patients in group 2, were reviewed. It was determined that intraoperative and postoperative narcotic analgesic consumption (p < 0.005), PONV (p < 0.005), and the first mobilization time (p < 0.005) were significantly lower in group 1 compared with group 2. CONCLUSION: The use of the ESP block in belt lipectomy surgeries significantly reduces intraoperative and postoperative narcotic analgesic consumption and pain scores. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Agomelatine potentiates anti-nociceptive effects of morphine in a mice model for diabetic neuropathy: involvement of NMDA receptor subtype NR1 within the raphe nucleus and periaqueductal grey.

OBJECTIVES: Opioid analgesics have been used for a long time in the treatment of acute and chronic pain. However, they have many side effects including tolerance development to a significant extent. Agomelatine, an atypical antidepressant, has been demonstrated to be effective in experimental studies on pain. However, the effect of agomelatine on morphine tolerance development and its mechanism of action are unknown. The antinociceptive effects of agomelatine, morphine and their combination were assessed in a mice model for painful diabetic neuropathy. The roles of glutamate ionotropic receptor N-methyl-D-aspartate (NMDA) type subunit-1 (GluN1) in raphe nucleus and periaqueductal gray (PAG) in the effect of agomelatine on neuropathic pain were also investigated in diabetic mice. METHODS: Agomelatine (10 mg/kg), morphine (10 mg/kg) and agomelatine + morphine were administered intraperitoneally for 15 consecutive days (twice per day), and the analgesic responses were assessed at days 1, 3, 6, 9, 12 and 15 in healthy and diabetic mice. Real time polymerase chain reaction (RT-PCR) was used to determine the changes in GluN1 expression. RESULTS: The tolerance development for morphine was evident, started at 6th day and remained thereafter, but not for agomelatine. GluN1 in raphe nucleus and PAG was upregulated in morphine treated but not in agomelatine-treated groups. DISCUSSION: The combination of agomelatine with morphine alone causes outlasting analgesic effects of repeated treatment, which can be interpreted as attenuated tolerance. Moreover, we also pointed out for the first time the modulatory effects of agomelatine on GluN1 expression in raphe nucleus and PAG after chronic morphine treatment. ABBREVIATIONS: Ca2+: Calcium; D2DR: Dopamine D2 receptor; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase; GluN1: Glutamate ionotropic receptor N-methyl-D-aspartate type subunit-1; 5-HT: 5-hydroxytryptamine; i.p.: intraperitoneal injection; MPE: Maximal possible effect; MT: Melatonin; NMDA: N-methyl-D-aspartate; NMDAR1: NMDA receptors-1; PAG: Periaqueductal grey; PKCγ: Protein kinase C gamma; RT-PCR: Real time polymerase chain reaction; STZ: Streptozotocin.

[Effective pain therapy can improve the survival of patients with pancreatic cancer]. / Etkin agri tedavisi pankreas kanserli hastalarda sagkalimi artirabilir.

OBJECTIVES: In this study, characteristics and analgesic treatment of patients with pancreatic cancer who applied to the algology clinic were evaluated. METHODS: Demographic characteristics, pathologic diagnosis, metastasis, cancer treatment, and analgesic interventions in 60 patients with pancreatic cancer, referred to the algology clinic, were examined. RESULTS: The application time of the patients to the clinic was 3.9+-0.92 months after the diagnosis, and the visual analog scale (VAS) was 6.96+-0.11 at the initial assessment. According to the analgesic step ladder protocol, a nonopiod + weak opioid + strong opioid (transdermal) were applied in 58.33%, a nonopioid + weak opioid + strong opiod (oral) in 5%, and nonopiod + weak opioid in 36.66% of the patients. Adjuvant pain medications were used in 68.33% of the patients (benzodiazepine, 80.48%; antidepressant, 19.51%), while no adjuvant was used in 31.66% of the patients. While the mean survival time for patients with pancreatic cancer changed from 3 to 6 months, it was 8.48+-7.46 months for patients who applied to the pain clinic. CONCLUSION: Abdominal pain in pancreatic cancer is the most common symptom that negatively affects the quality of life. A good analgesia improves the survival, while pain decreases the survival. The results of the present study demonstrated that the survival of the patients with metastatic pancreatic cancer who received effective pain therapy in the algology clinic may be longer.

The Relationship Between the Preoperative Neutrophil-to-Lymphocyte Ratio and Postoperative Nausea and Vomiting in Patients Undergoing Septorhinoplasty Surgery.

BACKGROUND: Postoperative nausea and vomiting (PONV) is one of the most common complications during the postoperative period. In the literature, there are many factors associated with PONV risk, but it is claimed that inflammation increases this risk. The neutrophil-to-lymphocyte ratio (NLR) is a cheap parameter to use in the diagnosis and follow-up of systemic inflammatory diseases. In this study, we aimed to investigate whether the preoperative NLR was a marker for PONV and to determine its relation with antiemetic use. METHODS: Eighty patients who were planned to undergo elective septorhinoplasty and were in ASA I-II were prospectively included in the study. The NLR value was calculated by dividing the number of neutrophils by the number of lymphocytes obtained from the preoperative complete blood count. The patients were divided into two groups of 40 patients: patients with an NLR < 2 (group 1) and patients with an NLR > 2 (group 2). Nausea and vomiting during the first 24 h in the recovery room and in the related clinic and antiemetic requirement were recorded. RESULTS: The rate of nausea-vomiting in the recovery room and in the postoperative 24-h period in group 1 was significantly lower than in group 2 (p < 0.05). The rate of use of antiemetics in the recovery room and in the postoperative 24-h period in group 1 was significantly lower than in group 2 (p < 0.05). CONCLUSION: NLR values above 2 calculated in the preoperative period may be an indicator of PONV risk. Antiemetic prophylaxis may be given according to this value. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Agomelatine pretreatment prevents development of hyperglycemia and hypoinsulinemia in streptozotocin-induced diabetes in mice.

The main objective of this study was to investigate potential effectiveness of agomelatine pretreatment in the prevention of diabetes itself and encephalopathy, with a focus on brain tissue oxidative stress and inflammatory processes in streptozotocin (STZ)-induced diabetic mice. Interleukine-1ß (IL-1ß) and TACR1 (NK1), which is a tachykinine receptor, were used for the investigation of inflammation in the brain regions including raphe nucleus, periaqueductal gyrus (PAG), amygdala, and nucleus accumbens. The effects of agomelatine on total antioxidant capacity were also evaluated. In the in vitro part of the study, the effects of agomelatine on cell viability were investigated in dorsal root ganglion (DRG) neurons. Fasting blood glucose levels were measured 72 h after STZ injection to determine the diabetic condition. Agomelatine pretreatment prevented both hyperglycemia and hypoinsulinemia in STZ-treated mice. When STZ was injected to induce diabetes in mice, neither hyperglycemia nor hypoinsulinemia was developed in agomelatine pretreated mice and 6 weeks after development of diabetes, agomelatine treatment significantly decreased levels of IL-1ß mRNA in raphe nucleus and nucleus accumbens. TACR1 mRNA levels were lower in raphe nucleus, PAG, and amygdala of agomelatine-treated diabetic mice. The increase in total antioxidant capacity after agomelatine administration may responsible for its beneficial effect in the prevention of diabetes. We showed that agomelatine reversed high glucose-induced cell viability decreases in DRG neurons. Both the antihyperglycemic and antioxidant effects of agomelatine might have contributed to the DRG neuron viability improvement. In conclusion, agomelatine seems to both prevent development of diabetes and reverse the encephalopathic changes caused by diabetes.

Agomelatine modulates calcium signaling through protein kinase C and phospholipase C-mediated mechanisms in rat sensory neurons.

Agomelatine, a novel antidepressant exerting its effects through melatonergic and serotonergic systems, implicated to be effective against pain including neuropathic pain but without any knowledge of mechanism of action. To explore the possible role of agomelatine on nociceptive transmission at the peripheral level, the effects of agomelatine on intracellular calcium ([Ca2+ ]i ) signaling in peripheral neurons were investigated in cultured rat dorsal root ganglion (DRG) neurons. Using the fura-2-based calcium imaging technique, the effects of agomelatine on [Ca2+ ]i and roles of the second messenger-mediated pathways were assessed. Agomelatine caused [Ca2+ ]i signaling in a dose-dependent manner when tested at 10 and 100 µM concentration. Luzindole, a selective melatonin receptor antagonist, almost completely blocked the agomelatine-induced calcium signals. The agomelatine-induced calcium transients were also nearly abolished following pretreatment with the 100 ng/ml pertussis toxin, a Gi/o protein inhibitor. The stimulatory effects of agomelatine on [Ca2+ ]i transients were significantly reduced by applications of phospholipase C (PLC) and protein kinase C (PKC) blockers, 10 µM U73122, and 10 µM chelerythrine chloride, respectively. The obtained results of agomelatine-induced [Ca2+ ]i signals indicates that peripheral mechanisms are involved in analgesic effects of agomelatine. These mechanisms seems to involve G-protein-coupled receptor activation and PLC and PKC mediated mechanisms.

Kisspeptin increases intracellular calcium concentration by protein kinase C-mediated signaling in the primary cultured neurons from rat hippocampus.

In addition to the fact that kisspeptin and its receptor GPR54 are well known to be abundantly expressed in the hypothalamus with suggestive roles in the initiation of puberty and similar reproductive system properties, there is also proof showing that kisspeptin might have influences on hippocampal functions. In our previous study, it was shown that kisspeptin increased free intracellular Ca2+ values ([Ca2+]i) through protein kinase C (PKC) activation in GT1-7 cells. For this reason, we examined the influences of kisspeptin on [Ca2+]i in hippocampal neurons to determine if kisspeptin shows its effects on hippocampus through the same mechanism. Hippocampal neurons were excised from the brains of fetuses on 17th embryonic day from maternal rats. The influences of kisspeptin on [Ca2+]i in hippocampal neurons were examined through in vitro calcium imaging system. The responses of [Ca2+]i to kisspeptin were quantified by the changes in 340nm/380nm ratio.  Kisspeptin-10 caused [Ca2+]i transients in hippocampal neurons. The change in [Ca2+]i by 100 nM kisspeptin was prevented by pre-treating the cells in PKC inhibitor chelerythrine chloride. According to the results, kisspeptin activates intracellular calcium signaling in hippocampal neurons via the pathway that depends on PKC. The results of this study suggest that kisspeptin may have a role in hippocampal neuron functions.

Intradiscal ozone therapy for lumbar disc herniation.

The rationale behind intradiscal O2-O3 therapy is the pain elicited by the mechanical compression of the nerve root, which is associated with periganglionic and periradicular inflammation. This study aimed to determine the effect of intradiscal ozone injection on pain score and satisfaction of patients with low back pain (LBP) secondary to disc herniation. Patients with LBP diagnosed with disc herniation were enrolled in this clinical trial. After prepping and draping the area, intradiscal injection of ozone/oxygen mixture (10 ml, 25µg/ml) was performed under fluoroscopy guide (c-arm). Pain score and patient satisfaction were assessed prior to the injection (baseline) and 1, 3, 6, 12 and 24 months after the injection. Sixty three patients (24 males, 39 females) with mean age of 53.3 ±2.0 y enrolled in the study. The mean±standard deviation (SD) of pain score before intervention was 6.968 ±0.11. Pain score was reduced to 4.25±0.19 at 1 month, 4.33±0.20 at 3 months, 4.87 ±0.21 at 6 months and 5.22 ±0.20 at 24 months. According to the modified MacNab scale success of pain relief was as follows: excellent: 4 (6.3%), good: 17 (26.98 %), sufficient: 13 (20.63 %), poor: 13 (20.63 %), no result: 11 (17.46%), negative: 4 (6.3 %). Intradiscal ozone therapy was determined to provide improved outcomes in patients with single level of bulging and protrusion.

Effects on QTc Interval of 2 Different Doses of Spinal Anesthesia in Inguinal Hernia Operations.

BACKGROUND Cardiac arrhythmia is a significant cause of morbidity and mortality. In this study, through examination of the effects on the QTc interval of different doses of hyperbaric bupivacaine, we investigated the relationship with arrhythmia. MATERIAL AND METHODS A total of 60 patients were separated into 2 groups: spinal block was applied with 10 mg bupivacaine to Group S1 and with 15 mg to Group S2. The mean arterial pressure (MAP) and heart rate (HR) values were recorded before the spinal block and at 5 and 30 min after the block and at 60 min postoperatively. By recording the time of the spinal sensory block to reach T10 dermatome (Anaesth T) and the duration of the surgical procedure (Surg T.), the QTc intervals were calculated. RESULTS The demographic data were similar in both groups. A statistically significant difference was determined between the S1 and S2 groups between the baseline and the 30 mins after spinal block QTc intervals (p=0.001). No statistically significant difference in HR values was determined between the groups at baseline, 5 min after spinal block, and 1 h after surgery (all p>0.05), but at 30 min after spinal block value there was a statistically significant difference (p=0.010). No statistically significant difference was determined in MAP values between the groups at baseline and 1 h after surgery (p>0.05). CONCLUSIONS The QTc interval lengthened in a dose-dependent manner after spinal anesthesia was applied with different doses of bupivacaine, but the doses used did not cause any severe arrhythmia.

Oxytocin activates calcium signaling in rat sensory neurons through a protein kinase C-dependent mechanism

In addition to its well-known effects on parturition and lactation, oxytocin (OT) plays an important role in modulation of pain and nociceptive transmission. But, the mechanism of this effect is unclear. To address the possible role of OT on pain modulation at the peripheral level, the effects of OT on intracellular calcium levels ([Ca2+]i) in rat dorsal root ganglion (DRG) neurons were investigated by using an in vitro calcium imaging system. DRG neurons were grown in primary culture following enzymatic and mechanical dissociation of ganglia from 1- or 2-day-old neonatal Wistar rats. Using the fura-2-based calcium imaging technique, the effects of OT on [Ca2+]i and role of the protein kinase C (PKC)-mediated pathway in OT effect were assessed. OT caused a significant increase in basal levels of [Ca2+]i after application at the doses of 30 nM (n = 34, p < 0.01), 100 nM (n = 41, p < 0.001) and 300 nM (n = 46, p < 0.001). The stimulatory effect of OT (300 nM) on [Ca2+]i was persistent in Ca2+-free conditions (n = 56, p < 0.01). Chelerythrine chloride, a PKC inhibitor, significantly reduced the OT-induced increase in [Ca2+]i (n = 28, p < 0.001). We demonstrated that OT activates intracellular calcium signaling in cultured rat primary sensory neurons in a dose- and PKC-dependent mechanism. The finding of the role of OT in peripheral pain modification may serve as a novel target for the development of new pharmacological strategies for the management of pain

Oxytocin activates calcium signaling in rat sensory neurons through a protein kinase C-dependent mechanism.

In addition to its well-known effects on parturition and lactation, oxytocin (OT) plays an important role in modulation of pain and nociceptive transmission. But, the mechanism of this effect is unclear. To address the possible role of OT on pain modulation at the peripheral level, the effects of OT on intracellular calcium levels ([Ca(2+)](i)) in rat dorsal root ganglion (DRG) neurons were investigated by using an in vitro calcium imaging system. DRG neurons were grown in primary culture following enzymatic and mechanical dissociation of ganglia from 1- or 2-day-old neonatal Wistar rats. Using the fura-2-based calcium imaging technique, the effects of OT on [Ca(2+)](i) and role of the protein kinase C (PKC)-mediated pathway in OT effect were assessed. OT caused a significant increase in basal levels of [Ca(2+)](i) after application at the doses of 30 nM (n = 34, p < 0.01), 100 nM (n = 41, p < 0.001) and 300 nM (n = 46, p < 0.001). The stimulatory effect of OT (300 nM) on [Ca(2+)](i) was persistent in Ca(2+)-free conditions (n = 56, p < 0.01). Chelerythrine chloride, a PKC inhibitor, significantly reduced the OT-induced increase in [Ca(2+)](i) (n = 28, p < 0.001). We demonstrated that OT activates intracellular calcium signaling in cultured rat primary sensory neurons in a dose- and PKC-dependent mechanism. The finding of the role of OT in peripheral pain modification may serve as a novel target for the development of new pharmacological strategies for the management of pain.