Classification of pain and their mechanisms are described in this chapter. Pain is classified into three categories according to the mechanisms; these are nociceptive pain, neuropathic pain and psychological pain. Nociceptive pain is caused by tissue damage and accompanies inflammation. Neuropathic pain is defined as pain arising as a direct consequence of a lesion or disease affecting the somatosensory system. Psychological pain is pain that is particularly attributable to the thought process, emotional state, or personality of the patient in the absence of an organic or delusional cause or tension. The characteristics of these different types of pain and methods of pain assessment are also described.
The ascending pain pathway consists of many complex neural structures, including specialized nociceptive receptors and peripheral nociceptive neurons in the dorsal root ganglion, spinal dorsal horn nociceptive and wide-dynamic range neurons, that play a role in the initial central neural processing for nociceptive information, several divergent relay stations (the thalamic nuclei and several nuclei in the brainstem) that properly mediate a variety of reflex reactions to painful stimuli, and are variously distributed among the thalamo-cortical and limbic circuits for sensory perception, learning, memory and other cognitive activity, and emotional responses. In addition to the ascending pain pathway, there are descending pathways that modulate pain by inhibiting nociceptive transmission. The purpose of the present review is to summarize the current knowledge of the structure of the pain system, including both the ascending and the descending components.
We describe the therapies used in pain clinics, such as nerve block therapy and photo-therapy, for intractable, chronic, non-cancer pain. When starting these therapies, we first need to comprehend the pain that afflicts the patients. Secondly, we have to check the therapy that the patients have already received. There are various mechanisms that can induce intractable pain, therefore we believe that it is useful to elucidate the mechanisms using drug challenge test for the management of pain. However, we should recognize that the pain mechanism can be very complicated and that there are some cases in which the pain mechanism will not be elucidated even when we use drug challenge test. Various kinds of nerve block therapies, such as stellate ganglion block, epidural block, thoracic sympathetic ganglion block, lumbar sympathetic ganglion block and intercostals nerve block, etc., are used for the management of intractable pain. On the other hand, there are many patients who cannot be treated with nerve block because of old age, complication and bleeding tendency, etc. In these patients, photo-therapy including irradiation with a low reactive level laser, linear polarized near infrared radiation and xenon light, may be alternatively selected because these therapies rarely induce complications. If pain relief is not obtained using nerve block or photo therapies, other therapies should be considered either alone or in combination.
Neuropathic pain is characterized by partial or complete somatosensory change in the innervation area corresponding to peripheral or central nervous system pathology, and the paradoxical occurrence of pain and hypersensitivity phenomenon within the denervated area and its surroundings. The management of patients with neuropathic pain is complex and the response to conventional treatment is often inadequate. Treatment of neuropathic pain is still difficult despite new therapeutic approaches, and there is no single treatment that works for all conditions and their underlying mechanisms. Appropriate diagnosis and assessment are critical to the successful treatment of neuropathic pain in each patient. The best way to relive neuropathic pain is considered to be with pharmacologic treatment. Evidence-based clinical recommendations for pharmacotherapy are necessary. Recommended first-line treatments include antidepressants (tricyclic antidepressant) and antiepileptics (gabapentin and pregabalin). Opioid analgesics are generally recommended as a second-line treatment. To reduce the number of patients who suffer from neuropathic pain, the physician should be familiar with neuropathic pain and should prescribe adequate medications based on recommended first-line treatments. However, unfortunately, the pharmacologic treatments for neuropathic pain are limited, with no more than 40-60% of patients obtaining partial pain relief of their pain. Ongoing development of new medications for neuropathic pain, additional trials involving existing medications alone and in combination are needed to advance the management of neuropathic pain.
For the treatment of intractable neuropathic pain, drug challenge test is necessary and useful to examine the pharmacological background of the pain in each case. Based on the results of drug challenge test, we can select the candidates for low-dose ketamine drip infusion (LDKDI) therapy and cerebrospinal stimulation therapy. In cerebrospinal stimulation therapy, dual-lead spinal cord stimulation should be selected at first, since we can insert electrodes percutaneously and this is suitable for both the test stimulation and chronic implantation. For the treatment of peripheral deafferentation pain, which includes phantom limb pain and peripheral nerve injury pain, deep brain stimulation therapy of the thalamic relay nucleus is suitable. Motor cortex stimulation therapy is suitable for the treatment of central deafferentation pain, which includes post-stroke pain. LDKDI therapy combined with cerebrospinal stimulation therapy achieves remarkable pain reduction in the treatment of neuropathic pain.
There are many patients with chronic pain who are referred from each of the clinical fields to the department of psychosomatic medicine. Various psychosocial stress factors participate in the onset of chronic pain. Psychological symptoms, such as anxiety, anger, depression, hypersensitivity, or irritation, are often related to the onset of chronic pain and change the state of illness. Chronic pain of the musculoskeletal system is often a pathologic reaction against the stress. Because a correlation between physical symptoms and psychological stress factors has been observed, chronic pain can be regarded as a representative form of psychosomatic disease. To improve efficacy in the medical treatment or psychotherapy, it is important to understand the psychosocial condition of chronic pain through sufficient history taking or appropriate psychological tests. For the pharmacological treatment of such chronic pain modified with psychosomatic factors, antianxiety drugs, antidepressants or anticonvulsants may be more effective than general analgesics or physical therapy. Holistic and specialized approaches, such as cognitive therapy or behavioral therapy, may be necessary for the treatment of chronic pain related to improper recognition, obsessive ideas or misunderstanding of the problems.
We report a case of small cell lung cancer with metastasis without any lesion in the lungs. The patient was 55-year-old man who visited to the hospital with dizziness. He underwent general examinations and enhanced-magnetic resonance imaging (MRI) of the head revealed that a lesion with ring enhancement sign in the cerebellum. Despite the fact that no lesions were detected in his lungs in chest computed tomography (CT), mediastinal lymph node enlargement and elevated levels of ProGRP in serum indicated an unknown primary small cell lung cancer and its brain metastasis. A biopsy of No. 3 lymph node performed by mediastinoscopy revealed small-cell lung cancer (SCLC). The patient was treated with chemotherapy after the diagnosis, and although the treatment was effective temporarily, the patient died 18 months after the diagnosis.
A 58-year old female suffering from cough, sputa, and dyspnea was referred to our hospital in June 1999. She was diagnosed with small cell lung cancer by lung biopsy. Serum LDH and NSE were increased. She achieved complete remission with chemotherapy (CDDP+Etoposide and CPA+DXR+VCR). In February 2000, acute monocytic leukemia (FAB classification M5b) with abnormal karyotype, t (8;16), developed. After induction therapy with IDR and Ara-C, partial remission was achieved. She discontinued follow-up at our hospital as of April 2003. In 2005, diffuse large B cell lymphoma (DLBCL) was identified in her right breast. Re-examination of the lung biopsy specimen obtained in 1999 revealed positivity for CD 20, suggesting B cell lymphoma. Despite the use of strong chemotherapeutics against DLBCL, her condition deteriorated and she died in September 2007. We suspect that the case was probably therapy-related leukemia, although concomitant occurrence of de novo leukemia in an NHL patient could not be refuted. We discuss the differences between therapy-related and de novo leukemia in the present case and review the literature.
Two males (aged 51 and 66 years) underwent emergent coronary artery bypass grafting for acute myocardial infarction. After surgery, they were diagnosed with severe sleep apnea syndrome (SAS) and left ventricular dysfunction. They were treated for SAS with continuous positive airway pressure (CPAP) therapy. After the CPAP therapy, these two patients not only improved their left ventricular function but also decreased the levels of A and B-type natriuretic peptides, renin-angiotensin-aldsterone indices, high sensitivity CRP, and oxidative LDL. SAS is common in cardiovascular disease and is a potential cause of increased mortality. The deteriorative effects of SAS on cardiac function have recently received attention because SAS has been found to increase cardiac afterload, stimulate sympathetic nerve activity, and induce myocardial ischemia. We conclude that CPAP therapy for SAS patients with left ventricular dysfunction is effective for left ventricular function, RAAS hormones, catecholamine, inflammation and oxidative stress.
A 60 year-old male who had undergone four-vessel coronary artery bypass grafting (CABG) due to severe ischemic cardiomyopathy and prior myocardial infarction was admitted to our hospital for implantation of autologous bone marrow cells via a retrograde coronary venous catheter. Myocardial blood flow and ejection fraction were evaluated by stress myocardial scintigraphy four weeks, six months and 36 months after implantation. It was revealed that myocardial perfusion was significantly improved throughout the follow-up period associated with relief of angina pain, but that enhancement of ejection fraction was temporarily observed only at the 6-month follow-up.
A 70-year-old man was referred to our hospital for a cystic lesion carcinoma of the right upper lobe. He had undergone surgery for right pneumothorax in another hospital, and the resected cyst wall obtained during the surgery revealed squamous cell carcinoma. For lung cancer, we performed right upper lobectomy. Pathological examination showed squamous cell carcinoma from the pseudostratified epithelium and bronchial glands. The conclusion was squamous cell carcinoma arising in a bronchogenic cyst wall. Reports of lung cancer in a bronchogenic cyst wall are very rare. As there were little if any changes in the cyst wall, we recommend complete resection of the bronchogenic cyst.
We report a case of a 68-year-old male with schizophrenia in which Yokukansan was effective in alleviating several psychotic symptoms. The patient exhibited irritability, insomnia and aural hypersensitivity during treatment with aripiprazole. These symptoms disappeared after we treated the patient with Yokukansan. We consider that it might be possible to treat a schizophrenic patient with a combination of antipsychotics and Yokukansan. However, to date, there have been few reports of schizophrenic cases treated with Yokukansan. Therefore, the findings of this report should be interpreted cautiously. In order to confirm the present findings, more case reports of schizophrenia patients treated with Yokukansan will be needed.