Correlation Between DNA Methylation of TRPA1 and Chronic Pain States in Human Whole Blood Cells.

OBJECTIVES: Neuro-immune interactions with functional changes in the peripheral blood cells including changes in the transient receptor potential ankyrin 1 (TRPA1) appear to play a pivotal role in the development of chronic pain in humans. The aim of this study was to examine the association between TRPA1 DNA methylation in whole blood cells and the pain states in chronic pain patients. METHODS: After collecting blood samples from 12 chronic pain patients, the authors measured DNA methylation levels in whole blood cells. Significant associations between the patient's demographic data and the chronic pain states were determined by a multiple linear regression analysis that used age, body mass index, pain duration, depression, anxiety, cognitive impairment, activities of daily living, neuropathic pain, and pain states as the dependent variables, and the TRPA1 DNA methylation levels as the independent variables. RESULTS: Multiple regression analysis revealed a significant correlation between increases of the methylation levels of the CpG island in the TRPA1 gene and increases in the number of neuropathic pain symptoms, which were evaluated using the Douleur Neuropathique 4 (DN4) questionnaire. Decreases in the TRPA1 mRNA expression were also significantly related to increases in the DN4 score. The presence of a burning sensation, which is one of pain symptoms in the DN4 questionnaire, was significantly correlated with the increase in DNA methylation level of TRPA1. CONCLUSIONS: TRPA1 DNA methylation levels in whole blood cells appear to be associated with pain symptoms in chronic pain patients.

Peripherally increased artemin is a key regulator of TRPA1/V1 expression in primary afferent neurons.

BACKGROUND: Artemin, a member of the glial cell line-derived neurotrophic factor family, is known to have a variety of neuronal functions, and has been the subject of attention because it has interesting effects, including bi-directional results in modulation in neuropathic and inflammatory pain. It has been shown that the overexpression of artemin is associated with an increase in the expression of TRP family channels in primary afferents and subsequent hyperalgesia, and an increase in neuronal activity. The purpose of this study was to examine the peripheral synthesis of artemin in inflammatory and neuropathic pain models, and to demonstrate the effects of long-term or repeated application of artemin in vivo on pain behaviors and on the expression of TRP family channels. Further, the regulatory mechanisms of artemin on TRPV1/A1 were examined using cultured DRG neurons. RESULTS: We have demonstrated that artemin is locally elevated in skin over long periods of time, that artemin signals significantly increase in deep layers of the epidermis, and also that it is distributed over a broad area of the dermis. In contrast, NGF showed transient increases after peripheral inflammation. It was confirmed that the co-localization of TRPV1/A1 and GFRα3 was higher than that between TRPV1/A1 and TrkA. In the peripheral sciatic nerve trunk, the synthesis of artemin was found by RT-PCR and in situ hybridization to increase at a site distal to a nerve injury. We demonstrated that in vivo repeated artemin injections into the periphery changed the gene expression of TRPV1/A1 in DRG neurons without affecting GFRα3 expression. Repeated artemin injections also induced mechanical and heat hyperalgesia. Using primary cultured DRG neurons, we found that artemin application significantly increased TRPV1/A1 expression and Ca(2+) influx. Artemin-induced p38 MAPK pathway regulated the TRPV1 channel expression, however TRPA1 upregulation by artemin is not mediated through p38 MAPK. CONCLUSIONS: These data indicate the important roles of peripherally-derived artemin on the regulation of TRPV1/A1 in DRG neurons in pathological conditions such as inflammatory and neuropathic pain.

[Case of negative pressure pulmonary edema after administration of sugammadex under general anesthesia with laryngeal mask airway].

We experienced a case of negative pressure pulmonary edema (NPPE) after administration of sugammadex under general anesthesia with LMA Supreme. Sugammadex was administered to a 76-year-old female patient following spontaneous ventilation. Immediately after the administration of sugammadex, laryngospasm occurred, and the patient's oxygen saturation dropped to 70%. About five minutes after the appearance of laryngospasm, she started to breathe spontaneously. However, a chest x-ray at this time showed pulmonary edema We suspected that sugammadex administration had triggered the laryngospasm, causing postoperative NPPE. When selecting a LMA under general anesthesia for airway management, we have to keep in mind the possibility of NPPE followed by laryngospasm.

[Use of the air-Q intubating laryngeal airway for tracheal intubation in predicted difficult airway management in a pediatric patient].

The intubating laryngeal airway, air-Q ILA, was recently introduced in Japan. It has been used in adult patients for difficult airway management; however, there are few reports available on its use in pediatric patients. We report the use of the air-Q ILA in predicted difficult airway management in a 16-month-old patient with Apert syndrome characterized by acrocephalosyndactyly undergoing a syndactyly operation. It was somewhat difficult to keep his airway with a facemask, and an air-Q ILA was inserted. Following the ventilation via air-Q ILA, tracheal intubation guided by a tracheal fiberscope was attempted through the air-Q ILA. Five months after this operation, the patient again underwent the same operation. We managed his airway in the same way as previously, and the tracheal was intubated. This case shows that the air-Q ILA can be an alternative device in pediatric difficult airway management.

Induction of the P2X7 receptor in spinal microglia in a neuropathic pain model.

Peripheral nerve injury causes a progressive series of morphological changes in spinal microglia, and extracellular ATP stimulates proliferation of microglia and may be involved in neuropathic pain. We defined the precise expression of P2X7 in the spinal cord following peripheral nerve injury. We found that both P2X7 mRNA and protein increased in the spinal cord, with a peak at 7d after injury. Double labeling studies revealed that cells expressing increased P2X7 mRNA and protein after nerve injury were predominantly microglia in dorsal horn. Pharmacological blockades by intrathecal administration of a P2X7 antagonist (A 438079 hydrochloride) suppressed the development of mechanical hypersensitivity. We present distinct evidence that increases in the number of P2X7 receptors in spinal microglia may play an important role in neuropathic pain.

[Combined epidural-spinal anesthesia for radical hysterectomy in a patient complicated with bronchiectasis diagnosed on preoperative anesthetic consultation].

A radical hysterectomy was performed in a patient complicated with bronchiectasis, under combined spinal-epidural anesthesia. The patient was asymptomatic and preoperatively diagnosed with bronchiectasis on an anesthetic consultation with an anesthesiologist. An epidural catheter was inserted between T12 and L1, and spinal anesthesia was subsequently performed with 0.5% bupivacaine 2.8 ml and fentanyl 10 microg. It was necessary to administer a supplemental epidural dose of 0.375% ropivacaine fifty minutes after the start of the operation. Postoperative epidural analgesia was effective and no perioperative complications were observed.

[Intra-atrial vegetation removal in a 14-month-old boy complicated with postoperative infective endocarditis and left middle cerebral artery embolism].

We report a case of the intra-atrial vegetation removal under cardiopulmonary bypass (CPB) in a case complicated with left middle cerebral artery embolism caused by postoperative infective endocarditis. The patient was a 14-month-old boy. Two months after intracardiac repair for a complex congenital heart disease, he presented with low-grade fever and was placed on oral antibiotics. A month later an echocardiography revealed 2 vegetations on the tricuspid valve. Although the vegetations became smaller with intravenous antibiotics, right hemiplegia was noted 5 weeks later. Brain CT and MR-angiography demonstrated left middle cerebral artery embolism. For fear of another embolism caused by a remaining movable vegetation on the tricuspid valve, intra-atrial vegetation removal under CPB was performed 5 days after cerebral infarction. Intraoperative transesophageal echocardiography was utilized to locate the vegetation and confirm its removal. His postoperative course was uneventful without a recurrence of cerebral infarction or bleeding. He was weaned from the ventilator on postoperative day (POD) 1, started to move the right extremities on POD 5 and was discharged home on POD 66.

[7-year survey of anesthesia for cesarean section--comparison of tetracaine and bupivacaine as intrathecal anesthetic agents].

BACKGROUND: In our institution, spinal anesthesia is the first choice for cesarean section. After the introduction of bupivacaine in 2000 in Japan, the intrathecal anesthetic agent shifted from tetracaine to bupivacaine. We analyzed the anesthesia for cesarean section in recent 7 years and compared the anesthetic quality of tetracaine with that of bupivacaine. METHODS: The anesthetic records were reviewed in the patients who had received cesarean section between January 1998 and December 2004 at our institution. RESULTS: There were 10456 deliveries during the study period with a cesarean section rate of 28.2% (2947 cases). Ninety-one percent of cesarean section was performed under spinal anesthesia. Spinal anesthetic agent shifted from tetracaine to bupivacaine in 2000-2001, both of which was prepared as a hyperbaric solution and supplemented with 0.1 mg of morphine hydrocloride. Of the 2711 patients in whom a cesarean section was started under spinal anesthesia, 20 (0.7%) required conversion to general anesthesia. Three hundred eighteen patients (11.7%) required some analgesic supplementation. The incidence of intra-operative analgesic supplementation was greater in the patients anesthetized with hyperbaric tetracaine and morphine than in those anesthetized with hyperbaric bupivacaine and morphine (22.96% vs 4.20% ; P<0.01). The conversion rate from spinal to general anesthesia for cesarean section was 0.7%. CONCLUSIONS: Comparing these two intrathecal anesthetic agents, the rate of analgesic supplementation in those anesthetized with bupivacaine was lower than in those anesthetized with tetracaine. This suggests that bupivacaine provides the more profound blockade of the visceral pain than tetracaine, and is superior as a local anesthetic.

[Anesthetic management of a child with Noonan syndrome and hypertrophic obstructive cardiomyopathy].

Noonan syndrome is characterized by facial, skeletal and cardiovascular anomalies. We describe the anesthetic management of a one-year-old boy with Noonan syndrome and hypertrophic obstructive cardiomyopathy scheduled for tonsillectomy and adenoidectomy under general anesthesia. He had a history of congestive heart failure at 5 months of age. Preoperative echocardiogram revealed a hypertrophied septum (12.8 mm) with concentric hypertrophy of the left ventricle. Mild mitral regurgitation was also noted. Our anesthetic goal was set to maintaining adequate preload and afterload as well as adequate anesthesia depth to avoid LV outflow tract obstruction. Intravenous fluid was started the day before surgery. Anesthesia was induced with fentanyl 30 microg and midazolam 2 mg and maintained with propofol 8 mg x kg(-1) x hr(-1), fentanyl 30 microg, ketamine 4 mg, and sevoflurane 1-2%. Intraoperative monitoring included 12-lead electrocardiogram and direct measurement of arterial pressure. Intra- and post-operative course was uneventful.