Neurotrophic factors and their cognate receptors regulate the development of the nervous system of vertebrates. During the embryonic period, most primary nociceptive neurons die in the absence of an adequate supply of one target-derived trophic factor, nerve growth factor (NGF) or its receptor tropomyosin receptor kinase A (TrkA). Adult primary sensory neurons continue to be sensitive to several neurotrophic factors; about one half of primary nociceptive neurons express receptors for NGF and the other half of them express receptors for another neurotrophic factor, glial-derived neurotrophic factor (GDNF). Both NGF and GDNF control the expression of various receptors and neurotransmitters in primary nociceptive neurons. The altered availability of these factors in cases of nerve or tissue injury is a key cause of altered properties of primary nociceptive neurons.
There is increasing evidence that NGF plays a role in the hyperalgesia associated with inflammation. An increase in the tissue level of NGF occurs within hours of the initiation of inflammation. A single dose of NGF produces prolonged thermal and mechanical hyperalgesia. The thermal hyperalgesia results, in part, from sensitization of nociceptors, while mechanical hyperalgesia involves central changes. In addition to the direct actions on nociceptors, NGF induces hyperalgesia by indirect mechanisms; for instance, NGF causes mast cell degranulation that leads to the release of mediators such as serotonin and histamine.
NGF locally produced by inflammation is retrogradely transported, and triggers the upregulation of tetrodotoxin-resistant Na channels (TTXr) in the cell body of nociceptive primary sensory neurons within the dorsal root ganglion. In contrast, an axonal injury results in the downregulation of TTXr and the upregulation of a previously unexpressed, tetrodotoxin-sensitive Na channel subtype, TTXs αIII. Thus, the membrane of nociceptive primary sensory neurons is retuned, and there are changes in its electrogenic properties which can poise it to fire inappropriately. The changes in the expression of Na channels can be reversed by peripherally applied NGF.
A third neurotrophic factor, brain-derived neurotrophic factor (BDNF) is made by primary nociceptive neurons expressing TrkA. NGF transported to the cell body upregulates BDNF synthesis. BDNF is transported to central terminals in dense core vesicles and released from central terminals. BDNF in turn phosphorylates the NMDA receptor, and thus modulates the excitability of secondary nociceptive neurons within the spinal cord.

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Recently, endoscopic thoracic sympathicolysis (ETS) has been established for primary palmary hyperhidrosis (PPH). Postoperative pain after ETS is rather severe, in spite of the small incision used for the surgical procedure. The aim of this study is a comparison of the two different analgesics for postoperative pain in ETS.
Forty-five patients were randomly assigned to the following three groups. Group B comprised 15 patients who received buprenorphine suppository before and after operation. Group F comprised 15 patients who received flurbiprofen axietil before and after operation. Group BF comprised 15 patients who received buprenorphine suppository before operation and flurbiprofen axietil after operation.
Postoperative pain was evaluated by using Prince Henly Pain Score (PHPS). Operation and anesthesia time, PaCO₂ after extubation, frequency of nausea and vomiting, and dose of antiemetics and analgesics were recorded simultaneously.
In the B group, PHPS and PaCO₂ after extubation were significantly higher (p<0.05) than those of the other groups just after ETS. Frequency of analgesics administered in the B group was also significantly higher (p<0.05) than that of other groups just after ETS. Our findings suggest that flurbiprofen axietil is suitable for postoperative pain after ETS.

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Introduction: Hyperhidrosis is distressing and a source of intense embarrassment. Numerous methods of sympathectomy, including open thoracotomy, as well as posterior and supraclavicular approaches have been performed. Endoscopic thoracic sympathectomy (ETS) is a new approach for hyperhidrosis patients. However, it is still unclear about changes in sympathetic nerve function after ETS.
Methods: 38 subjects with hyperhidrosis were enrolled in this study. Assessments of sympathetic skin response (SSR) and thermography were performed to evaluate sympathetic nerve activity before and 1, 3, 6 and 12 months after ETS. Total amount of sweat and core temperature of a hand were also measured. Thermatome was made by thermography to investigate the range of upper thoracic sympathetic nerve innervation.
Results: Results showed 76 hands became dry and SSR disappeared in all subjects just after the operation. Four of 38 subjects showed recurrence of sweat within 12 months of recovery. In these 4 subjects, SSR appeared before sweat reappeared in their palms again.
Thermography showed that the sin temperature of face, upper limbs, upper trunk, and bilateral palms was significantly increased. Nine thermatomes were classified by thermography. Most patients showed compensatory hyperhidrosis.
Conclusion: These results suggest that SSR is a valuable method to assess the sympathetic function after ETS and could be a parameter for anticipating prognosis. The upper thoracic sympathetic nerve may innervate a wide area, such as face, upper limb and upper trunk.

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Postherpetic neuralgia (PHN) is recognized to be treatment-resistant and may persist for many years, causing decrease in quality of life (QOL) and depression in some patients. Electroconvulsive therapy (ECT), of which effects on depression are well established, has been reported to reduce intolerable pain associated with depression. We have already reported that ECT reduces pain and allodynia in PHN. In this study, we examined long term effects of ECT on PHN.
Subjects were 7 males and 3 females with PHN. Two patients had nociceptive pain arising from bone metastasis of hepatocellular carcinoma or rheumatoid arthritis, (RA) in addition to PHN. Based on written consent from the patients and their families, a course of bilateral ECT (110V for 5sec, 6 or 12 times with interval of one to seven days) was performed. Long term effects were assessed in terms of pain score on persisitent pain, area of allodynia, frequency of intermittent pain, quality of life (QOL) and Hamilton Depression Scale (HDS) 5 to 43 months after the first course of ECT.
In all patients, the first course of ECT gave relief or remarkable reducation of pain and allodynia, except for the pain due to bone metastasis or RA, and the QOL of the patients was improved. Besides improvement of pain, the depression lessened. Hypesthesia in involved dermatome remained unchanged, and nociception in the healthy skin remained inact. The pain and allodynia gradually recurred in the skin area with hypesthesia several months after the first course, while HDS remained unchanged.
Another course of ECT was applied in seven patients 5 to 26 months after the first course. The second course, consisting of a smaller number of ECT trials, produced the same analgesic effects and fewer side effects of amnesia.
Those results suggest that PHN patients are less tolerant to the analgesic effects of ECT than they are to morphine administration or motor cortex stimulation, hewe, ECT is a possible treatment for established PHN.

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We have opened the first homepage related to Anesthesia in Japan (http://hypnos.m.ehime-u.ac.jp/Masuika/index-j.html) on the internet. We have begun to make our pain clinic web page (http://hypnos.m.ehime-u.ac.jp/Pain_memo/index-j.html) on the internet as a review to keep abreast of new ideas and treatments in this field of medical practice. The topics are arranged alphabetically for the reader's convenience. To publicize on the internet, we had to add needed tags to the text file for html (hypertext makeup language). Then we uploaded the file to our UNIX machine (hypnos), moved to the directory of Pain _memo/index-j.html and renamed the file. We then linked this file to the Pain_memo/index-j.file, clicked the reload button and confirmed the file on our web site.
We can link these files to the referential files of our computer freely. We can add new treatments or revise the contents more quickly than in any books.

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WHO cancer pain relief guidelines embodied in the “analgesic ladder” have received wide acknowledgment. However, the guidelines have not specifically referred to problems in older cancer patients. There have been very few studies that have addressed the impact of physiological, psychological and social factors on the assessment and management of cancer pain in elderly patients. In this study we tried to determine characteristics of pain management in older cancer patients.
Methods: We conducted a survey addressing the above issues in Japanese hospices and palliative care units using a questionnaire which required two kinds of answers in each of 53 clinical pain management areas. One kind of answer concerned the clinical importance of cancer pain management, and the other involved the difference between cancer pain management in elderly patients compared with younger patients.
Results: Eighteen sets of answers were returned, with 85% of clinical pain management answers being rated as either very important or important, and 30% of the same answers indicating age-related pain management differences. With respect to pain assessment, important aspects included: defining the cancer pain; assessment of pre-existing chronic pain; assessment of the patient's medical, psychological and social status; performing appropriate laboratory and radiographic tests; and developing a pain-oriented problem list. In general pain management, important aspects were: treating the underlying organic contribution to the pain by radiotherapy, chemotherapy and/or surgery; giving psychological, social and physical rehabilitation; using a multimodal approach; and considering age-related physiological changes that may influence the patient's response to any intervention. Regarding pharmacotherapy, important aspects were: choosing an appropriate drug in accordance with the WHO three-steps ladder; beginning with low doses; being aware of additive effects; continuing each drug trial for an adequate duration; using fixed schedules and “as needed” dosing appropriately; using an appropriate route of administration; and anticipating and treating side effects, especially sedation and confusion.
Conclusion: It is important to be aware of, and to respond to physiological, psychological and social factors when managing cancer pain in elderly patients.

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