Tatsunori Ikemoto

Effects of experimental focal compression on excitability of human median motor axons

OBJECTIVE To characterize the effect of focal compression by threshold tracking and other excitability measures of human median motor axons. METHODS We conducted a sequence of excitability studies using a software written in BASIC (QTRAC version 4.0, (c)Institute of Neurology, London, UK, with multiple excitability protocol TRONDXM 2) in 24 healthy subjects, stimulating the median nerve at the wrist and recording compound muscle action potentials from the abductor pollicis brevis. Constant, localized compression was applied at the wrist by mechanically lowering a probe attached to a disk electrode, which also served as the stimulating cathode. RESULTS Compared with the pre-compression values, measurements during compression showed a shift of threshold electrotonus waveforms toward the baseline (fanning-in), steeper current-threshold relationships, increased strength-duration time constants, prolonged relative refractory periods and reduced levels of superexcitability, but no alteration in late subexcitability. These excitability changes indicating depolarization reversed to hyperpolarization immediately after release of compression. The nerve compression altered none of the excitability measures when recorded 2 cm distally from the pressure probe. CONCLUSIONS Mild nerve compression produces a very localized axonal depolarization at the compression site followed by hyperpolarization upon release of compression, as expected from focal ischemia. SIGNIFICANCE The current results imply that the sharply-localized conduction abnormalities demonstrated electrophysiologically in peripheral nerve entrapment syndromes and compression myelopathies may, in part, result from compression-induced focal nerve ischemia.

Visualization of Painful Experiences Believed to Trigger the Activation of Affective and Emotional Brain Regions in Subjects with Low Back Pain

In the management of clinical low back pain (LBP), actual damage to lower back areas such as muscles, intervertebral discs etc. are normally targeted for therapy. However, LBP may involve not only sensory pain, but also underlying affective pain which may also play an important role overall in painful events. Therefore we hypothesized that visualization of a painful event may trigger painful memories, thus provoking the affective dimension of pain. The present study investigated neural correlates of affect processing in subjects with LBP (n = 11) and subjects without LBP (n = 11) through the use of virtual LBP stimuli. Whole brain functional magnetic resonance imaging (MRI) was performed for all subjects while they were shown a picture of a man carrying luggage in a half-crouching position. All subjects with LBP reported experiencing discomfort and 7 LBP subjects reported experiencing pain. In contrast to subjects without LBP, subjects with LBP displayed activation of the cortical area related to pain and emotions: the insula, supplementary motor area, premotor area, thalamus, pulvinar, posterior cingulate cortex, hippocampus, fusiform, gyrus, and cerebellum. These results suggest that the virtual LBP stimuli caused memory retrieval of unpleasant experiences and therefore may be associated with prolonged chronic LBP conditions.

Virtual Pain Stimulation of Allodynia Patients Activates Cortical Representation of Pain and Emotions: A Functional MRI Study

Summary:The present study investigated neural correlates of affect processing in allodynia patients (n=8) and healthy controls (n=12) with the aid of virtual tactile stimulation. Whole brain functional magnetic resonance imaging was performed for allodynia patients and healthy volunteers while they were shown a video demonstrating light stimulation of the palm and another stimulation aimed at producing anticipation of palm stimulation. Contrasting with controls, patients displayed activation of the cortical areas related to pain and emotions: prefrontal cortex (Brodmanns area BA 10) and anterior cingulate cortex (BA 24). These findings may indicate involvement of an emotional component of pain perception in all odynia patients.

Changes in calcitonin gene-related peptide expression following joint immobilization in rats

Long-term immobilization by casting can occasionally cause pathologic pain states in the immobilized side. The underlying neurophysiological mechanisms of immobilization-related pain are not well understood. For this reason, we specifically examined changes of calcitonin gene-related peptide (CGRP) expression in the dorsal root ganglion (DRG), spinal dorsal horn and posterior nuclei (cuneate nuclei) in a long-term immobilization model following casting for 5 weeks. A plastic cast was wrapped around the right limb from the forearm to the forepaw to keep wrist joint at 90 degrees of flexion. In this model, CGRP in immobilized (ipsilateral) side was distributed in larger DRG neurons compared with contralateral side, even though the number of CGRP-immunoreactive (CGRP-IR) neurons did not differ. Spinal laminae III-V, not laminae I-II in ipsilateral side showed significantly high CGRP expression relative to contralateral side. CGRP expression in cuneate nuclei was not significantly different between ipsilateral and contralateral sides. Long-term immobilization by casting may induce phenotypic changes in CGRP expression both in DRG and spinal deep layers, and these changes are partly responsible for pathological pain states in immobilized side.

Chronic Pain in the Japanese Community—Prevalence, Characteristics and Impact on Quality of Life

Background Chronic pain is recognized as a public health problem that affects the general population physically, psychologically, and socially. However, there is little knowledge about the associated factors of chronic pain, such as the influence of weather, family structure, daily exercise, and work status. Objectives This survey had three aims: 1) to estimate the prevalence of chronic pain in Japan, 2) to analyze these associated factors, and 3) to evaluate the social burden due to chronic pain. Methods We conducted a cross-sectional postal survey in a sample of 6000 adults aged ≥20 years. The response rate was 43.8%. Results The mean age of the respondents was 57.7 years (range 20–99 years); 39.3% met the criteria for chronic pain (lasting ≥3 months). Approximately a quarter of the respondents reported that their chronic pain was adversely influenced by bad weather and also oncoming bad weather. Risk factors for chronic pain, as determined by a logistic regression model, included being an older female, being unemployed, living alone, and no daily exercise. Individuals with chronic pain showed significantly lower quality of life and significantly higher psychological distress scores than those without chronic pain. The mean annual duration of absence from work of working-age respondents was 9.6 days (range 1–365 days). Conclusions Our findings revealed that high prevalence and severity of chronic pain, associated factors, and significant impact on quality of life in the adult Japanese population. A detailed understanding of factors associated with chronic pain is essential for establishing a management strategy for primary care.

Virtual needle pain stimuli activates cortical representation of emotions in normal volunteers

Psychological factors are known to play an extremely important role in the maintenance and development of chronic pain conditions. However, it is unclear how such factors relate to the central neural processing of nociceptive transmission in healthy individuals. To investigate this issue, the activation of the brain was studied in 30 healthy volunteers responding to virtual pain stimuli by fMRI. In the first series of the study (non-preconditioned study), 15 participants were shown a digital video demonstrating an injection needle puncturing the right palm. In the second series of the study (pre-conditioned study), same-task paradigms were used for another 15 participants. Prior to the fMRI session, real needle punctuate stimuli were applied to the right palm of participants for pre-conditioning. fMRI analysis revealed that bilateral activations in anterior insula (BA45), parietal operculum (S2: BA40), premotor area, medial globus pallidus, inferior occipital gyrus (BA18), left temporal association cortex, right fusiform gyrus, right parietal association cortex and cerebellum occurred due to the task in the preconditioned group. On the other hand, right parietal operculum (S2: BA40), premotor area, parietal association cortex, left inferior frontal gyrus and bilateral temporal association cortex were activated in the non-preconditioned group. In addition, activation of anterior insula, inferior frontal gyrus, precentral gyrus and cerebellum significantly increased in the preconditioned group compared with the non-preconditioned group. These results suggest that the virtual needle puncture task caused memory retrieval of unpleasant experiences which is possibly related to empathy for pain, resulting in the activation of specific brain areas.

Alterations of Contralateral Thalamic Perfusion in Neuropathic Pain

Contralateral thalamus, the place of termination of spinothalamic tract, is affected in patients with pain. We employed single photon emission computed tomography (SPECT) to evaluate the thalamic perfusion in patients with spontaneous neuropathic pain. Ten patients with complex regional pain syndrome (CRPS) and eleven radiculopathiy patients were enrolled in this study. Regional cerebral blood flow of thalamus was assessed bilaterally by iodine-123-labelled iodoamphetamine SPECT. To standardize the inter-patient data, we set a contralateral thalamic uptake index (CTUI) for assessing thalamic asymmetry. In one study, we found elevation of CTUI in patients with symptoms of neuropathic pain for less than 12 month, whereas no change was observed in the case of a longer lasting disease. An another study demonstrated decrease of CTUI after pain treatment, even though it was unrelated to the pain intensity prior to treatment. Our SPECT study revealed that neuropathic pain altered thalamic neuronal activity. CTUIs were increased in early stage of the disease but decreased as the disease progressed to the chronic stage. These results suggest that CTUI can be used to improve management of neuropathic pain for proper evaluation of spontaneous pain.

The review of innovative integration of Kampo medicine and Western medicine as personalized medicine at the first multidisciplinary pain center in Japan

BackgroundThe Japanese medical system is unique because it is the only country in the world where Western medicine and traditional Japanese medicine including Kampo medicine, traditional Japanese herbal medicine, are used in our daily clinical practice. Pain is essentially an interactive psychophysiological behavior pattern. Thus, an interdisciplinary approach is often recommended in providing appropriate therapeutic care for the patients suffering from chronic and intractable pain. In addition, we have been prescribing Kampo medicines in combination with Western medicines as personalized medicine in order to treat patients with chronic pain at our pain center. The aim of our study was to conduct a survey on the current use and the effect of Kampo medicines in our multidisciplinary pain center.MethodsRetrospective analysis was performed on 221 out of 487 patients suffering from chronic pain.ResultsThe most frequent medical complaints for which Kampo medicines were prescribed were lower back/lower limb pain, neck/upper limb pain, various facial pains, headache/migraine, whiplash-associated disorder, and frozen shoulder. Kampo medicines were prescribed based on patient-centered Kampo diagnosis. Moreover, several Kampo medicines generally for the management of psychological symptoms were prescribed for about 70% of the patients. Pain improvement in the patients was categorized as follows: 26.3% with marked improvement, 12.7% with moderate improvement, 38.9% with some improvement, and 19.9% with no improvement.ConclusionsTwo thirds of the chronic pain patients with the use of Kampo medicines combined with Western medicine experienced further pain improvements.

The efficacy of a multidisciplinary group program for patients with refractory chronic pain

Comprehensive programs for chronic pain management provided at multidisciplinary clinics have been shown to be successful in Western countries. However, similar results have not yet been reported in Japan, and it is unclear whether these results are applicable to the Japanese culture. Accordingly, the authors report the results of the ‘Chronic Pain Class’, a program initiated at a multidisciplinary pain centre in Nagakute, Japan.

The Effect of the Kampo Medicine Yokukansan on Preoperative Anxiety and Sedation Levels

Background. Preoperative anxiety can lead to unfavorable physiological response such as tachycardia and hypertension. Prevention of preoperative anxiety improves surgical outcome and decreases inpatient stay. Yokukansan is one of prescriptions in Kampo, traditional Japanese herbal medicine, and is known to exert anxiolytic effects. The aim of the present study was to compare the effects of diazepam and Yokukansan on preoperative anxiety, salivary amylase activity, and sedation levels. Methods. Seventy American Society of Anesthesiologists physical status I or II patients presenting for hemicolectomy under general anesthesia combined with epidural anesthesia were enrolled. The Diazepam group received diazepam 5 mg orally and the Yokukansan group received Yokukansan 2.5 g orally. Results. Although levels of anxiety and salivary amylase activity were not different between the two groups, the modified Observers Assessment of Alertness/Sedation Scale of the Yokukansan group was significantly higher compared to that of the Diazepam group. Conclusion. Yokukansan alleviated preoperative anxiety without undesirable sedation, when compared with diazepam.