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Leukotriene B4 (LTB4) is a potent lipid mediator involved in the recruitment and activation of neutrophils, which is an important feature of tissue injury and inflammation. The biological effects of LTB4 are primarily mediated through the high-affinity LTB4 receptor, BLT1. Postoperative incisional pain is characterized by persistent acute pain at the site of tissue injury and is associated with local inflammation. Here, we compared the role of LTB4-BLT1 signaling in postoperative incisional pain between BLT1-knockout (BLT1KO) and wild-type (BLT1WT) mice. A planter incision model was developed, and mechanical pain hypersensitivity was determined using the von Frey test before and after incision. Local infiltration of neutrophils and inflammatory monocytes was quantified by flow cytometry. Inflammatory cytokine levels in the incised tissue were also determined. Mechanical pain hypersensitivity was significantly reduced in BLT1KO mice compared to BLT1WT mice at 2, 3, and 4 days after incision. LTB4 levels in the tissue at the incision site peaked 3 hours after the incision. Infiltrated neutrophils peaked 1 day after the incision in both BLT1KO and BLT1WT mice. The accumulation of inflammatory monocytes increased 1–3 days after the incision and was significantly more reduced in BLT1KO mice than in BLT1WT mice. In BLT1KO mice, Interleukin-1β and Tumor Necrosis Factor-α levels 1 day after the incision were significantly lower than those of BLT1WT mice. Our data suggest that LTB4 is produced and activates its receptor BLT1 in the very early phase of tissue injury, and that LTB4-BLT1 signaling exacerbates pain responses by promoting local infiltration of inflammatory monocytes and cytokine production. Thus, LTB4-BLT1 signaling is a potential target for therapeutic intervention of acute and persistent pain induced by tissue injury. [ABSTRACT FROM AUTHOR]

Background: Leukotriene B4 (LTB4) is a potent lipid mediator of inflammation, and its biological effects are mediated primarily through the high affinity LTB4 receptor BLT1. Although numerous studies have reported that LTB4-BLT1 signaling is involved in inflammatory diseases, the role of BLT1 signaling in pain remains undefined. To clarify the role of LTB4-BLT1 signaling in acute inflammatory pain induced by tissue injury, we performed pain behavioral analysis and assessment of local inflammation induced by peripheral formalin injections in BLT1 knockout mice. We examined the phosphorylation of cAMP response element-binding protein (CREB) in the spinal cord both in wild-type and BLT1 knockout mice because phosphorylation of CREB in spinal cord neurons is important for nociceptive sensitization following peripheral injury. We also examined the effect of a BLT1 antagonist on formalin-induced pain responses in mice., Results: BLT1 knockout mice exhibited markedly attenuated nociceptive responses induced by intraplantar formalin injections. Edema formation and neutrophil infiltration in the paw were significantly decreased in BLT1 knockout mice compared with wild-type mice. Phosphorylation of CREB in the spinal cord after the intraplantar formalin injection was decreased in BLT1 knockout mice. In addition, mice pretreated with a BLT1 antagonist showed reduced nociception and attenuated CREB phosphorylation in the spinal cord after the formalin injection., Conclusions: Our data suggest that LTB4-BLT1 axis contributes not only to the peripheral inflammation but also to the neuronal activation in the spinal cord induced by intraplantar formalin injections. Thus, LTB4-BLT1 signaling is a potential target for therapeutic intervention of acute and persistent pain induced by tissue injury.

Palliative esophageal bypass surgery for patients with esophageal cancer and esophagobronchial fistula aims restoring the ability of swallowing as well as preventing pulmonary aspiration. Perioperatively, there are several problems in respiratory management for such patients. Repeated episodes of pulmonary aspiration exaggerate bronchopneumonia. Positive pressure ventilation may cause air leakage via fistula resulting in inadequate ventilation, distension of the stomach and regurgitation of gastric contents; thus, maintaining of spontaneous ventilation is a crucial concern. Here we report an anesthetic management of a 51-year-old woman with esophageal cancer and esophagobronchial fistula undergoing esophageal bypass surgery. We could not apply neuraxial block due to hypocoagulability. We performed awake tracheal intubation, and general anesthesia was maintained using sevoflurane supplemented by morphine, fentanyl and ketamine under spontaneous ventilation until the resection of gastroesophageal junction and the installation of a drainage catheter into the esophagus. Muscle relaxation required for surgery was sufficiently obtained by sevoflurane anesthesia without administration of muscle relaxants. After the installation of the drainage catheter, the lungs were ventilated mechanically until the end of surgery. The surgery was uneventful. The patient emerged from general anesthesia smoothly, and was extubated. The postoperative course of this patient was also uneventful.

A 79-year-old man underwent aortic arch replacement for thoracic aortic aneurysm. He had a history of smoking, coronary stenting for ischemic heart disease and replacement with artificial blood vessel for abdominal aortic aneurysm. Anesthesia was induced and maintained with midazolam, fentanyl, sevoflurane, and vecuronium. A 20 gage catheter was placed in the right radial artery and a 22 gage catheter in the left posterior tibial artery. Total circulatory arrest under profound hypothermia and retrograde cerebral perfusion were performed using extracorporeal circulation. After finishing anastomosis with artificial blood vessel, he was weaned from extracorporeal circulation. The pressure in the left posterior tibial artery was maintained at 15 mmHg, although the blood pressure in the right radial artery increased gradually. Then, the pressure in the left femoral artery in the operative field was the same as the pressure in the right radial artery. Therefore, we suspected the arterial line occlusion of the left posterior tibial artery. After the operation, we found the left leg and foot pale and cold with no pulsation on the left popliteal, dorsal pedis, and posterior tibial arteries. Further, acute left popliteal arterial occlusion was assessed by means of Doppler and left lower extremity angiography. We immediately performed the balloon-catheter embolectomy. However, as he developed compartment syndrome on the left lower limb due to reperfusion injury postoperatively, fascitomy was performed. On the 58th postoperative day, he was discharged from our hospital. Measurement by Doppler is useful for the early diagnosis of the lower leg arterial occlusion.

Drug challenge test (DCT) is performed to evaluate chronic pain pharmacologically and determine its medical treatment. One test drug is administered in one day for DCT and characterization of the test drug. Four patients developed side effects of the test drugs for DCT in whom other drug tests were postponed or canceled. A 58-year-old man with multiple arthritis of rheumatic arthritis and fibromyalgia had headache, nausea, and vomiting all day after ketamine test. A 76-year-old man with chronic general pain and failed back surgery syndrome had vomiting and abdominal discomfort two hours after morphine test and had redness and itching on his bilateral forearms the following day. A 78-year-old man with chronic lumbar and right lower limb pain due to L 4-5 lumbar disc herniation and postherpetic neuralgia felt dizzy, fell down and bruised on his lower back and left knee twelve hours after morphine test. A 32-year-old woman with chronic pelvic pain had skin eruption on her thigh the day after phentolamine test. Although the amount of the test drug in DCT is small and its half-life is short, long-term side effects might occur. We should decrease the amounts or frequencies of ketamine and morphine, and administer them taking long intervals before other tests.