Push-Through Myringoplasty Versus External Auditory Canal Flap Tympanoplasty for Chronic Marginal Perforations.

OBJECTIVE: We compared the operation times, graft success rates, and hearing gains between push-through (PT) myringoplasty and external auditory canal (EAC) flap tympanoplasty in patients with chronic marginal perforations. MATERIALS AND METHODS: A total of 77 patients with chronic marginal perforations were randomly allocated to endoscopic perichondrium-cartilage myringoplasty with raising of the EAC flaps (n = 39) and PT technique (n = 38) groups. The graft outcomes, mean operation times, and postoperative complications were compared 6 months after operation. RESULTS: The graft success rate was 97.4% (38/39) in the EAC group and 81.6% (31/38) in the PT group; the difference was significant (P = .056). The mean operation time was 40.7 ± 10.4 min in the EAC group and 42.4 ± 8.3 min in the PT group (P = .741). In the EAC group, the mean pre- and postoperative air-bone gap (ABG)s were 29.3 (range: 28.4 ± 8.6) and 12.1 (range: 11.8 ± 2.4) dB (P < .01), respectively; the respective values were 29.5 (range: 29.1 ± 5.4) and 12.6 (range: 12.0 ± 1.3) dB (P < .01) in the PT group. No significant group difference was observed in the pre- (P = .794) or postoperative (P = .689) ABG values or mean ABG gain (16.7 ± 5.3 vs 17.1 ± 7.7 dB; P = .526). In addition, graft medialization occurred in 7.9% patients in the PT group. However, graft lateralization, significant blunting, deteriorative sensorineural hearing loss, vertigo, or tinnitus were not encountered in either group. No taste change was reported and no inclusion cholesteatoma was seen in the EAC group. CONCLUSION: Endoscopic perichondrium-cartilage myringoplasty with raising of an EAC flap is useful and minimally invasive to repair chronic marginal perforations; the technique is simple, has a high graft success rate in comparison to the PT technique.

Hemodynamics in Patients With Pheochromocytoma or Paraganglioma Undergoing Non-neuroendocrine Operations.

INTRODUCTION: Surgical resection of pheochromocytoma and paraganglioma (PPGL) may be associated with excessive hemodynamic variability. Whether hemodynamic variability occurs in patients with undiagnosed PPGL undergoing unrelated, non-neuroendocrine, operations is unknown. METHODS: We identified patients who underwent non-neuroendocrine surgical procedures up to 5 y before pathologic diagnosis of PPGL. For each PPGL, two non-PPGL patients were matched based on sex, age, type, and year of operation. Electronic medical records were reviewed for intraoperative blood pressures, heart rates, and hemodynamic variability was assessed with range (maximum-minimum), standard deviation, coefficient of variation, and average real variability. RESULTS: Thirty-seven PPGL patients underwent operations preceding the diagnosis of PPGL: 25 pheochromocytomas, 11 paragangliomas, and one metastatic pheochromocytoma. Median interquartile range tumor size at diagnosis was 35 mm (23 to 60). The time from index operation to PPGL diagnosis was ≤12 mo in 21 (56.8%) patients. In 23 (62.2%) patients, the subsequently diagnosed PPGL was functional. Fifteen (40.5%) PPGL and 20 (27.0%) control patients were preoperatively treated for hypertension (P = 0.149). Maximum intraoperative systolic BP was >180 mmHg for 4 (10.8%) PPGL patients and 3 (4.1%) controls (P = 0.219). Two PPGL patients had intraoperative systolic BP >230 mmHg. No significant differences were found with all other measures of intraoperative hemodynamic variability. Similarly, in secondary analysis there was no significant difference in intraoperative hemodynamic variability between biochemically active PPGL and their respective controls. CONCLUSIONS: Patients with undiagnosed PPGL undergoing a wide variety of non-neuroendocrine operations had intraoperative hemodynamic variability comparable to non-PPGL patients undergoing the same type of procedures.

Excising or preserving perforation margins in endoscopic transtympanic cartilage myringoplasty does not affect surgical success.

OBJECTIVE: To compare the outcome of endoscopic transtympanic cartilage myringoplasty with and without removal of perforation edges for repairing chronic perforations with mucosal chronic otitis media (COM). STUDY DESIGN: Quasi-randomised clinical trial. SETTING: Tertiary referral centre. MATERIALS AND METHODS: Patients with chronic perforations and mucosal COM undergoing endoscopic transtympanic cartilage myringoplasty were allocated to a control group for whom the perforation edges were preserved (n = 40) and an intervention group for whom the edges were removed (n = 39). Mean operation time, graft success rate, mean scores of graft neovascularisation and epithelialisation, and hearing were compared between the groups at 4 weeks and/or 6 months postoperatively. RESULTS: Graft success rate was 95% (38/40) in the control group and 97% (38/39) in the intervention group at 6 months postoperatively; the difference was not significant. Mean graft neovascularisation scores 4 weeks postoperatively were 2.52 ± 0.59 in the control group and 2.58 ± 0.55 in the intervention group; the difference was not significant. Mean graft epithelisation scores 4 weeks postoperatively were 1.48 ± 0.57 in the control group and 1.68 ± 0.51 in the intervention group; the difference was not significant and remained nonsignificant 6 months postoperatively (2.5 ± 0.55 vs. 2.76 ± 0.36). Audiological outcomes at 6 months did not differ between the groups. CONCLUSION: Endoscopic, transtympanic cartilage underlay myringoplasty with preservation of the perforation margins did not affect graft neovascularisation, epithelialisation or success. Longer-term outcomes and risk of cholesteatoma require further study.

Comparison of long-term outcome of two endoscopic transtympanic myringoplasty without tympanomeatal flap elevating for repairing large chronic perforations.

OBJECTIVE: We compare the long-term efficacy of the cartilage-perichondrium modified over-underlay technique and transtympanic underlay alone technique using endoscopic myringoplasty without tympanomeatal flap elevating for repairing large chronic perforations. MATERIAL AND METHODS: Nine chronic large perforations with mucosal chronic otitis media were recruited and randomly allocated to endoscopic cartilage-perichondrium modified over-underlay myringoplasty (MOUM, n = 55) and endoscopic cartilage-perichondrium transtympanic underlay alone myringoplasty (TUAM, n = 54). The graft success rate, hearing gain, mean operation time and postoperative complications were compared between the groups at 6 and 24 months. RESULTS: In total, 99 patients were finally analysed. The graft success rates 6 months after surgery between MOUM and TUAM groups were not significantly different (100.0% vs 96.0%, p = 0.484). However, the MOUM group had a significantly higher success rate 24 months after surgery than the TUAM group (93.9% vs 76.0%, p = 0.028). In addition, postoperative ABG < 10 dB was 73.5% patients in the MOUM group and 76.0% in the TUAM group, the difference wasn't significant (p = 0.953). CT examination revealed well-pneumatised middle ears 24 months after surgery in both groups, and no middle ear cholesteatoma was observed. CONCLUSION: Endoscopic modified cartilage-perichondrium over-underlay myringoplasty without tympanomeatal flap elevating is reliable and effective for repairing large perforations. It improves the long-term graft success rate compared to the endoscopic cartilage-perichondrium transtympanic underlay alone technique. The risk for iatrogenic cholesteatoma is minimal.

Cox-2 Antagonizes the Protective Effect of Sevoflurane on Hypoxia/Reoxygenation-Induced Cardiomyocyte Apoptosis through Inhibiting the Akt Pathway.

OBJECTIVE: To uncover the protective role of sevoflurane on hypoxia/reoxygenation-induced cardiomyocyte apoptosis through the protein kinase B (Akt) pathway. METHODS: An in vitro hypoxia/reoxygenation (H/R) model was established in cardiomyocyte cell line H9c2. Sevoflurane (SEV) was administrated in H9c2 cells during the reoxygenation period. Viability, layered double hydroxide (LDH) release, and apoptosis in H9c2 cells were determined to assess H/R-induced cell damage. Relative levels of apoptosis-associated genes were examined. Moreover, phosphorylation of Akt was determined. RESULTS: H/R injury declined viability and enhanced LDH release and apoptotic rate in H9c2 cells. Cyclooxygenase-2 (Cox-2) was upregulated following H/R injury, which was partially reversed by SEV treatment. In addition, SEV treatment reversed changes in viability and LDH release owing to H/R injury in H9c2 cells, which were further aggravated by overexpression of Cox-2. The Akt pathway was inhibited in H9c2 cells overexpressing Cox-2. CONCLUSIONS: Sevoflurane protects cardiomyocyte damage following H/R via the Akt pathway, and its protective effect was abolished by overexpression of Cox-2.

Endoscopic inlay cartilage and perichondrium myringoplasty for repairing large perforations in teenagers.

OBJECTIVE: This study compared the long-term graft success rates and hearing outcomes of overlay-underlay and underly cartilage myringoplasty for repairing large perforations in Teenagers. STUDY DESIGN: prospective, randomized study. SETTING: Tertiary referral center. METHODS: Pediatric patients older than 12 years with chronic perforations were randomly divided into two groups:intervention group (n = 39) and control group (n = 41). The graft success rate, hearing improvement, and complications were compared between the two groups. RESULTS: A total of 80 patients were included in this study. The graft success rate was 100% in the intervention group and 95.1% in the control group at postoperative 3 months, the difference wasn't significant (P = 0.496). Also, the graft success rate was not significantly different between the two groups at 12 months postoperatively (100.0% vs 87.8%, p = 0.073). However, the difference of graft success rate was significant between the two groups at 24 months postoperatively (97.4% vs 75.6%, p = 0.012). CT examination revealed well-pneumatized middle ears 24 months after surgery in both group. However, epithelial pearls near the umbo were seen at 31 months postoperatively in one patient in the observation group. CONCLUSIONS: Compared to the endoscopic cartilage with perichondrium composite graft underlay technique, endoscopic perichondrial graft overlay and cartilage underlay had a better long-term graft success rate and lower rate of long-term re-perforation in teenagers. However, the graft technique had no effect on hearing outcome.

Microwave ablation eustachian tuboplasty: a preliminary investigation with long-term follow-up.

OBJECTIVES: This study was performed to evaluate the efficacy of microwave ablation (MWA) eustachian tuboplasty for the treatment of patients with retracted tympanic membrane (TM) due to eustachian tube dysfunction (ETD). METHODS: This was a prospective study of 20 patients with ETD (middle ear atelectasis) who underwent MWA eustachian tuboplasty. Outcomes included the ability to perform a Valsalva maneuver, audiometry results, tympanometry results, ETD Questionnaire (ETDQ-7) score, and TM status. RESULTS: Eighteen patients (18 ears) were included in this study. There were statistically and clinically significant improvements in the mean ETDQ-7 score at 6 months postoperatively (change in mean score of 16.7 ± 3.6, P < 0.001) and at 30 months postoperatively (change in mean score of 18.9 ± 2.9, P < 0.001). Type A tympanogram was obtained in 27.8% of patients (5/18) at 6 months postoperatively, and in 77.7% at 30 months postoperatively. A Valsalva maneuver was possible in 72.2% of patients at 6 months postoperatively and in 88.9% of patients at 30 months postoperatively. In addition, the ears of 13 patients (72.2%) showed both normal tympanograms and TM at 30 months postoperatively. Interestingly, 38.5% of patients (5/13) exhibited complete sclerosis of the pars tensa. None of the patients experienced severe MWA-related complications during follow-up. CONCLUSIONS: MWA eustachian tuboplasty is a feasible alternative to conventional tuboplasty, and can improve subjective and objective outcomes in patients with ETD for up to 30 months following treatment. In addition, this study showed that the extent of sclerotic plaque increased over time, whereas the extents of atrophy and tensa retraction decreased following tuboplasty in most patients.

Postoperative ethmoid sinus mucoceles: Late complication of endoscopic ethmoidectomy and MWA management in outpatient.

OBJECTIVE: The aim of this study was to investigate the feasibility of intranasal endoscopic microwave ablation (MWA) on the management of postoperative ethmoid sinus mucoceles. METHODS AND MATERIALS: The patients with postoperative ethmoid sinus mucoceles were ablated through intranasal endoscopic MWA. Postoperative pain intensity was measured via visual analogue scale (VAS), post-operative complications were recorded. RESULTS: Of the 26 patients with unilateral postoperative ethmoid sinus mucoceles, the mucoceles were diagnosed 3 to 11 years with average time of time of 6.9 ± 2.7 years after endoscopic ethmoidectomy. The ipsilateral middle turbinate was present and intact in 24 patients and partially resected during the original surgery in the remaining 2. There were adhesions in the middle meatus in one case. All 26 patients were successfully treated with the intranasal endoscopic ablation technique in outpatient. The ablation time was 6 to 11 min, with an average duration of 6.84 ± 1.27 min. The mean VAS pain score was 2.41 ± 1.22. There were no perioperative complications reported in this series. No evidence of recurrence was observed in any patients during follow-up periods. CONCLUSIONS: The present study demonstrates the safety and efficacy of intranasal endoscopic MWA in the office. The procedure is well tolerated by patients with low complication rates. Thus, it is alternative to conventional endonasal endoscopic marsupialization for treatment of postsurgical ethmoid sinus mucoceles.

MicroRNA­421 attenuates macrophage­mediated inflammation by inhibiting PDCD4 in vitro.

The exact pathogenesis of acute lung injury (ALI) has not been fully clarified. Previous studies have demonstrated that ALI is associated with inflammation. Recent studies have demonstrated that microRNA­421 (miR­421) prevents inflammation in cerebellar ischemia reperfusion injury. However, the role of miR­421 in ALI remains unclear. The present study investigated the role of miR­421 in ALI and the mechanism underlying this. ALI was induced in vitro by treatment of RAW 264.7 macrophages with lipopolysaccharide (LPS). Cells were then transfected with miR­421 mimic, miR­421 mimic control, programmed cell death 4 (PDCD4) siRNA and PDCD4 siRNA control using Lipofectamine 2000. Cell viability was measured using the Cell Counting kit­8. Reverse transcription­quantitative polymerase chain reaction was used to detect the expression of miR­421 and PDCD4 in RAW 264.7 macrophages. The concentrations of IL­1ß and TNF­α were detected by ELISA. Dual­luciferase reporter assays were used to investigate the interaction between miR­421 and PDCD4 mRNA. LPS inhibited cell viability and miR­421 expression. The miR­421 mimic promoted RAW 264.7 cell viability and inhibited the expression of iNOS and COX­2 as well as the release of IL­1ß and TNF­α. PDCD4 siRNA inhibited the expression of iNOS and COX­2 expression as well as the release of IL­1ß and TNF­α. In addition, miR­421 mimic and PDCD4 siRNA inhibit the expression of p­NF­κB (p65) in RAW 264.7 cells. In conclusion, the present study demonstrated the protective effect of miR­421 on ALI and showed that miR­421 attenuates LPS­induced ALI by inhibiting PDCD4 and NF­κB. These findings provided a theoretical basis for the treatment of ALI.

Effect of intraoperative blood transfusion on Treg and FOXP3 in patients with digestive tract malignancies and different ABO blood types.

BACKGROUND: Blood transfusion can cause immunosuppression and lead to worse outcomes in patients with digestive tract malignancies; however, the specific mechanism behind this is not completely understood. One theory is that increased numbers of regulatory CD3+CD4+CD25+FOXP3+ T cells (Tregs) and forkhead box protein-3 mRNA (FOXP3) expression in the blood after transfusion contribute to these outcomes. The effect of blood transfusion on immune function in patients with different ABO blood types is variable. This study investigates the effect of intraoperative blood transfusion on the number of Tregs and the expression of FOXP3 in the blood of patients with different ABO blood types and digestive tract malignancies. METHODS: Patients with digestive tract malignancies who underwent radical resection and received intraoperative blood transfusion were divided into four groups according to their blood types:blood group A, blood group B, blood group O and blood group AB (n = 20 for each group). Blood was collected from all patients before surgery, immediately after transfusion, 1 day after transfusion, and 5 days after transfusion. The number of Tregs was measured by flow cytometry. The expression of FOXP3 was detected by real time reverse transcription polymerase chain reaction (RT-PCR). RESULTS: There was no significant difference in the number of Tregs or expression of FOXP3 mRNA among patients with different blood types before surgery. However, the number of Tregs and the expression of FOXP3 increased after blood transfusion in all blood type groups. This increase was especially evident and statistically significant on the first day after blood transfusion when compared with measures obtained before the surgery. Measures returned to the preoperative level five days after surgery. There were significant differences in the increase of Tregs and expression of FOXP3 among patients with different blood types. The greatest increase was seen in patients with blood group B and the least in blood group A. CONCLUSIONS: Intraoperative blood transfusion can lead to an increase in blood Tregs and FOXP3 expression in patients with digestive tract malignancies. Increases were greatest on the first day after surgery and differed among patients with different blood types. Increases were greatest in blood type B and least in blood type A.

The feasibility of intranasal endoscopic microwave ablation on the removal of nasolabial cyst: Preliminary case series.

OBJECTIVE: The aim of this study was to investigate the clinical effect of the removal of nasolabial cyst via intranasal endoscopic microwave ablation (MWA). METHODS AND MATERIALS: The patients with nasolabial cyst were ablated through intranasal endoscopic MWA. Postoperative pain intensity was measured via visual analogue scale (VAS), post-operative complications were recorded. RESULTS: Of the 31 patients with unilateral nasolabial cyst, the main complaint was a gradually increasing mass in the nasal alar and upper lip, other complaint included nasal obstruction (11/31,35.5%), localized pain (21,67.7%), and erythema (13/31,41.9%). All 31 patients were successfully treated with the intranasal endoscopic ablation technique in outpatient. The mean ablation duration was 5.86 ± 0.71 min. The mean VAS pain score was 2.36 ± 1.08 on postoperative. None of infection occurred. All the patients complained of mild numbness in the upper lip with an average last duration of 28.5 ± 7.9 h in patients. In addition, 4 (12.9%) patients had facial/perinasal swelling, acid bilge of maxillary teeth in 7(22.6%), and toothache in one (3.2%). The patients were followed up for 12 months without recurrence and oronasal fistula. The nasolabial cyst had integrated into a part of the nasal cavity. CONCLUSIONS: The intranasal endoscopic MWA is feasible and alternative to conventional transoral sublabial approach for removal of the nasolabial cysts in outpatient.

Is no de-squamatization of the TM reliable for cartilage over-underlay myringoplasty without external auditory canal packing?

OBJECTIVE: We evaluated the graft and hearing outcomes of patients with chronic perforations treated via the cartilage-perichondrium over-underlay technique without de-squamatization of the TM and external auditory canal (EAC) packing. MATERIALS AND METHODS: Thirty-nine patients with chronic perforations and residual tympanic membranes around the perforation margins were treated using the cartilage-perichondrium over-underlay technique without de-squamatization of the TM and EAC packing. Patients were followed-up for 6 months. RESULTS: For all 39 patients with unilateral perforations, the graft success rate was 100% (39/39) at 6 months after surgery. The mean air-bone gap significantly (P < 0.05) improved from 13.41 ± 8.34 dB preoperatively to 7.45 ± 3.81 dB postoperatively in patients with small and medium perforations; the mean air-bone gap significantly improved from 20.57 ± 9.41 dB preoperatively to 9.84 ± 2.41 dB postoperatively in patients with large perforations. The lateral perichondrium gradually became necrotic and crust at postoperative 2-3 months and migrated into the EAC in all patients. CONCLUSIONS: The cartilage-perichondrium over-underlay myringoplasty without de-squamatization of the TM and EAC packing is feasible, affording a high graft success rate and good hearing improvement. The lateral perichondrium may gradually become necrotic and crusted, and migrate along the EAC over time.

The effect of concurrent nasal surgery on the eustachian tube function and myringoplasty outcomes.

OBJECTIVE: To investigate the Effect of concurrent nasal surgery on the eustachian tube function (ETF) and myringoplasty outcomes for the chronic perforations with coexistent nasal pathology. MATERIALS AND METHODS: We retrospectively reviewed the records of 93 patients with perforations who underwent same-day myringoplasty and nasal-septal surgery. Group A exhibited septal deviations (n = 34) and Group B inflammatory sinus disease (n = 59). Groups were compared with respect to pre- and postoperative air-bone gaps (ABGs), graft success rates and ETF (Eustachian tube score [ETS] and seven-item Eustachian Tube Dysfunction Questionnaire [ETDQ-7]) at 6 and 24 months. RESULTS: Graft success rates were 100.0% in Group A and 98.3% in Group B at 6 months postoperatively (P = 0.445). Graft success rates were 85.3% in Group A and 96.6% in Group B at 24 months postoperatively (P = 0.046), the re-perforation rate was significantly higher in Group A than in Group B (P = 0.015). Although the preoperative ETS was similar between two groups, the postoperative ETS in the Group B was significantly higher compared with Group A regardless of at postoperative 6th and 24th months. In addition, difference was significant for the patients with positive Valsalva maneuver among two groups at postoperative 24th months. Also, the improvement in the ETDQ-7 score in the B group was significantly higher than that in the A group at postoperative 6th and 24th months. CONCLUSIONS: Concurrent nasal surgery and myringoplasty is feasible. In addition, ESS improves ETF and thus long-term outcomes of myringoplasty for the chronic perforations with inflammatory sinus disease.

Microwave ablation for the removal of pharyngeal benign lesions: A prospective pilot case series.

OBJECTIVE: We evaluated microwave ablation (MWA) for treatment of isolated pharyngeal benign lesions, in terms of technical feasibility, efficacy, and safety. METHODS: The patients with pharyngeal benign lesions were treated with endoscopic MWA with a 2450-MHz single cooled-shaft microwave antenna and sent for histological examination. Postoperative pain intensity was measured via visual analogue scale (VAS) on the 12th hour and the third postoperative days. RESULTS: Of the 137 patients with pharyngeal benign lesions who met the inclusion criteria. The most commonly involved site was the uvula (n = 66, 48.2%), followed by the lateral pharyngeal wall (n = 37, 27.0%), the nasopharyngeal posterior wall (n = 23, 16.8%) and the soft palate (n = 11, 8.0%). All of the procedures were completed using local anesthesia and were well-tolerated by the patients. The ablation time was 5-10 min, with an average duration of 6.3 ± 1.8 min. The most common pathology was papilloma (n = 96, 70.1%), followed by nasopharyngeal cysts (n = 21, 15.3%), polyp (n = 10, 7.3%), epidermoid cysts (n = 8, 5.8%) and Thornwaldt cysts (n = 2, 1.5%). The mean VAS pain score was 2.36 ± 1.08 on postoperative 12th hour and 1.21 ± 0.54 on postoperative third day. At the 6-month follow-up examination, there were no severe complications, such as recurrence, bleeding, or synechiae of the nasal cavity, eustachian tube injury, in any of the patients. CONCLUSIONS: The MWA for the treatment of isolated pharyngeal benign lesion is feasible and alternative to conventional surgical methods, it allows excision of the lesion while providing hemostasis, involves only a short ablation time and has a very low risk of complications. Most of our patients well-tolerate the procedure, which may be performed under local anesthesia in the outpatient setting.

The COVID-19 pandemic and physical activity.

The SARS-CoV-2-caused COVID-19 pandemic has resulted in a devastating threat to human society in terms of health, economy, and lifestyle. Although the virus usually first invades and infects the lung and respiratory track tissue, in extreme cases, almost all major organs in the body are now known to be negatively impacted often leading to severe systemic failure in some people. Unfortunately, there is currently no effective treatment for this disease. Pre-existing pathological conditions or comorbidities such as age are a major reason for premature death and increased morbidity and mortality. The immobilization due to hospitalization and bed rest and the physical inactivity due to sustained quarantine and social distancing can downregulate the ability of organs systems to resist to viral infection and increase the risk of damage to the immune, respiratory, cardiovascular, musculoskeletal systems and the brain. The cellular mechanisms and danger of this "second wave" effect of COVID-19 to the human body, along with the effects of aging, proper nutrition, and regular physical activity, are reviewed in this article.

Pressure waveform-guided epidural catheter placement in comparison to the loss-of-resistance conventional method.

STUDY OBJECTIVES: To investigate pressure waveform-guided epidural catheter placement (PWEP) and its effect in clinical practice. DESIGN: Single-center, prospective cohort study. SETTING: University teaching hospital. PATIENTS: 3,326 patients undergoing thoracic, abdominal, and lower limb surgery. INTERVENTIONS: 1,614 underwent PWEP and 1,664 had the loss-of-resistance (LOR) technique. MEASUREMENTS: Anesthesia success and catheter replacement-related complications were recorded. MAIN RESULTS: The specificity and sensitivity of PWEP was higher than LOR, and it also provided higher satisfaction with anesthesia when compared with the LOR technique (62.8% vs 45.6 %; P < 0.05). PWEP also performed better than LOR in risk of anesthesia failure (0.4% vs 1.1%; P < 0.05) and catheter replacement-related complications (0% vs 0.6%; P < 0.05). CONCLUSION: PWEP is a reliable and useful technique for epidural catheter placement.

Effect of periaqueductal gray melanocortin 4 receptor in pain facilitation and glial activation in rat model of chronic constriction injury.

OBJECTIVES: Substantial evidence shows that spinal melanocortin 4 receptor (MC4R) may participate in regulation of central sensitization and chronic pain condition induced by peripheral nerve injury. Periaqueductal gray (PAG) is an important component of descending pain facilitatory system and takes part in spinal nociceptive information. This research will choose PAG to discuss the effect of MC4R in pain facilitation induced by chronic constriction injury (CCI) and further discuss its effect in glial activity and inflammatory factor levels in nerve injury. METHODS: Behavior tests (von Frey test and hot-plate test), semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), and immunohistochemistry were used in this research. RESULTS: PAG injection of HS014 (a selective inhibitor of MC4R), not only significantly reduced the established mechanical allodynia and thermal hyperalgesia, but also delayed the development of pain facilitation. Semi-quantitative RT-PCR analysis revealed that MC4R and proopiomelanocortin (POMC) expression in PAG was significantly increased after CCI, but agouti-related protein (AgRP) expression decreased. Immunohistochemistry analysis showed that protein levels of astrocytic marker (GFAP), microglial marker (OX-42), tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 were significantly increased, but there was little change of the protein levels of IL-10 following CCI. Furthermore, blockade of MC4R decreased immunoreactivity of glia cells and protein levels of pro-inflammatory cytokines, and increased protein levels of anti-inflammatory cytokine IL-10 after CCI. DISCUSSION: This research suggests that activation of MC4R in PAG after peripheral nerve injury participates in pain facilitation by regulating the glial activation and inflammatory cytokines secretion.