Recently, our understanding of the role of serine proteases such as thrombin has been expanded to include actions in the nervous system. Thrombin affects protease-activated receptors (PARs), which are a family of G protein-coupled receptors. It is considered that PARs are implicated in responses to injury, notably in inflammation and repair. In particular, PAR-1, which is one of a PAR subtype and mediates most of the known proinflammatory actions of thrombin, is expressed by platelets, endothelial cells, neurons and astrocytes. Furthermore, it has been reported that PAR-1 is expressed in subsets of primary sensory neurons, suggesting that PAR-1 may be implicated in pain perception.
It has been reported that thrombin induces the activation of platelets and promotes the expression or the release of platelet-derived growth factor (PDGF) from α-granule of platelets. Recent studies have demonstrated that PDGF and its receptor could be located in myelinated and unmyelinated primary sensory neurons and in the spinal cord. Thus, these findings support the idea that PDGF, which is mostly present in the blood vessels, may play an important role in the physiological responses including pain perception. Taken together, these findings raise the fascinating possibility that PDGF associated with PAR may be implicated in pain perception.
This review attempts to summarize the role of the spinal thrombin/PAR-and PDGF/PDGF receptor-mediated signaling pathways in the development of chronic pain-like state in mice.

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This is to introduce the results of the questionnaire survey that covered 1, 394 doctors recognized Japan Society for Pain Clinicians concerning incidents and accidents associated with nerve blocks.
Doctors representing 51.8% of those who were surveyed responded, of which 51.2% was valid.
The questionnaire involved 12 different nerve blocks including stellate ganglion block, epidural block and trigeminal nerve block.
It was revealed that many kinds of incidents and accidents occurred during the course of each nerve block procedure.
In addition, 154 doctors had troubles with patients due to incidents and accidents. Such troubles were largely solved by negotiation or private settlement, and cases that developed into lawsuit were few.

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We report in detail three patients with chronic intractable pain that responded very well to psychosocial approaches including advice for life-style change and the litigation procedure. In all three case studies given, this psychosocial approach resulted in better improvement than that obtained through conventional medical treatment such as surgery or medication administered orally or by injection. It is widely recognized that psychosocial factors generally play an important role in cases of chronic pain. This report seeks to call greater attention to the importance of this approach in the course of treating chronic pain.

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We treated two cases of Buerger's disease with autologous transplantation of peripheral blood-mononuclear cells (PB-MNC). In the first case, a man aged in his 70s complained of coldness and severe ischemic pain in his legs. Autologous transplantation of PB-MNC was carried out successfully. Although the pain and coldness relapsed in about 6 months, these symptoms immediately improved following lumbar sympathetic ganglion blocks (LSGBs) resulting in the patient's discharge. In the second case, a man aged in his 40s complained of severe ischemic pain, coldness, and ulcers in his legs. Because the effect of LSGBs was insufficient, autologous transplantation of PB-MNC was conducted under epidural anesthesia. The transplantation entailed severe edema and pain in his legs, which were managed by continuous epidural anesthesia and oral administration of codeine. The symptoms in his legs were improved after the transplantation. Therefore patients with Buerger's disease with were successfully treated autologous transplantation of PB-MNC. Adaptation of LSGBs and pain control in the transplantation therapy are important for the management of pain. Further examinations will be necessary to identify the appropriate timing of LSGB.

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Severe bleeding is a rare complication of lumbar sympathetic block (LSB). We report a case of intractable hemorrhage in the iliopsoas muscle following LSB. A woman in her fifties who required hemodialysis for diabetic nephropathy, presented with a painful refractory ulcer in her left foot. We performed LSB for pain management, which was uneventful. She was discharged the following day and underwent hemodialysis therapy with heparin at a nearby clinic.
On the 5th day after LSB she visited our hospital with severe pain in the left thigh. Her hemoglobin was decreased and computed tomography demonstrated a massive hematoma and active hemorrhage in the left iliopsoas muscle. She was started on conservative treatment including transfusion. To prevent the bleeding tendency, nafamostat mesilate was utilized for hemodialysis, however, she did not respond to the therapy. Angiography revealed hemorrhage from a branch of the second lumbar artery, and there was blood flow into the spine from the artery, making it impossible for her to undergo embolization. Fortunately, there was no drop in hemoglobin from the 22nd day.
On the 37th day she presented with hematemesis and tarry stool. Emergency gastrointestinal endoscopy showed bleeding from the duodenum. Hemostasis was achieved using hemostatic clips. However, angiography and magnetic resonance imaging did not detect any active hemorrhage in the iliopsoas muscle. The patient's clinical status improved and she was discharged on the 55th day.
In this case, it is clear that the hemodialysis with heparin was the major cause of iliopsoas hemorrhage. Because of the high bleeding risk, a number of precautions must be taken when nerve blocking hemodialysis patients, including careful observation and providing information to other organs involved in patient's treatment.

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There are many treatment modalities for complex regional pain syndrome (CRPS). However, there have been only a few reports of acupuncture and moxibustion for the treatment of CRPS type I. We report a patient who had CRPS type I of the upper limb who was treated with acupuncture and moxibustion. A 28-year-old woman developed severe pain and allodynia in the right upper limb after fracture of the right humerus. The pain was resistant to medications and repeated nerve blocks. The patient was referred to our department for pain treatment three years after the fracture. Acupuncture and moxibustion treatment were performed combined with stimulation of the meridians. The pain and ranges of motions of the shoulder and elbow joints improved during 1.5 months of treatment. We conclude that acupuncture and moxibustion treatment may be useful for some selected patients with CRPS type I.

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Morphine is often ineffective for cancer pain caused by bone metastasis. We partially applied transdermal fentanyl to a patient with cancer pain caused by bone metastasis who had received slow-release morphine, and observed a good pain-relieving effect. The patient had complained of severe pain in his back and legs. We at first used amitriptyline, ketamine, and lidocaine in addition to an increased dosage of morphine, which did not reduce the pain nor side effects such as nausea. We then partially employed transdermal fentanyl instead of morphine, and obtained a significant improvement of the pain as well as the side effects. The patient's blood concentration of morphine, morphine-6-glutamate (M6G), and morphine-3-glutamate (M3G) measured after the opioid rotation was 80, 355, and 2899ng/ml, respectively, and the proportion of morphine:M6G:M3G was 1:5:32. A possibility that the high blood level of M3G countered the analgesic action of morphine and M6G was considered. It was suggested that the absence of active metabolite in fentanyl contributed to its effectiveness. It was also suggested that another contributing factor was the combination of morphine and fentanyl that affected μ receptors of different subclasses. Opioid rotation from morphine to fentanyl is considered an acceptable treatment for cancer pain for which morphine is not effective.

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We report a case of a 60-years-old woman with postoperative cranial nerve palsies in the right side following neurosurgical operation who was successfully treated with repeated peripheral nerve block for persistent facial pain in the same side. Forteen months before visiting our outpatient pain clinic, she had an operation for giant vestibular schwannoma in the right side. Following the operation, cranial nerve dysfunction (IV, V, VI, VII, VIII, and IX) occurred probably caused by synechotomy of the tumor. She has had severe facial pain in the right side for 8 months before the visit. Repeated supraorbital, infraorbital, and maxillary nerve blocks with local anesthetic agent markedly alleviated the dysfunction of cranial nerves as well as facial pain during the first 2 months, and to date have been effective for >1 year. Since she experienced frequent shooting pain associated with the persistent dull pain, we speculate that her facial pain was neuropathic and her cranial nerve palsies were a result of cross-talk between sympathetic and injured trigeminal nerve. We also suspect that complex regional pain syndrome (CRPS) in her right facial area prolonged cranial nerve palsy and repeated nerve block on the peripheral trigeminal region alleviated the regional ischemia that would probably be induced by cross-talk. The present case suggests that such CRPS induced by this proposed mechanism should be differentially diganosed for the prolonged palsy of cranial nerves after surgical intervention for vestibular schwannoma.

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We report a patient whose lower limb pain caused by metastatic cancer was relieved by pulsed radiofrequency (PRF) to the lumbar nerve roots, without causing apparent sensory or motor dysfunction. A 61-year-old man had pain in the lower limb caused by metastatic cancer to the lumbar vertebrae. The pain was confined mainly to the right L5 and S1 dermatomes, and severely limited ambulation. Since sideeffects of oral oxycodone or morphine such as nausea/vomiting and somnolence made increase of the dose of opioid difficult, the pain was not controlled adequately. He did not give consent to neurolysis of the nerve roots with alcohol, phenol, or electrocautery. PRF was applied to the right L5 and S1 nerve roots, after which the pain gradually improved without causing sensory or motor dysfunction of the lower limb. Small doses of opioid could control the pain after PRF. We conclude that PRF may play an important role in the treatment of cancer pain involving the limbs.

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A 66-year-old man with long-standing intractable hiccup, which had improved by oral amitriptyline, propranolol, and clonazepam, with occasional vagus nerve blocks over 3 years and 2 months, developed intestinal obstruction. The hiccup recurred after cessation of the oral medications. Since conservative treatment did not improve the intestinal obstruction, the stenosed part of the ileum was resected. The hiccup gradually improved 2 weeks after surgery, even though oral medications had been discontinued. The hiccup disappeared 5 weeks after surgery. The stenosed ileum may have played a role in the pathogenesis of intractable hiccup in this patient.

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