Osafumi Yuge

Topographical features of cutaneous tactile hypoesthetic and hyperesthetic abnormalities in chronic pain

Tactile sensory abnormalities, such as tactile hypoesthesia and mechanical allodynia, are frequently present in patients with chronic pain. A growing body of evidence indicates that hyperesthetic phenomena, like mechanical allodynia, are at least in part due to altered processing by neurons in the CNS. We propose that the hyperesthesia is associated with a functional tactile hypoesthesia that is similarly mediated by altered processing by CNS neurons, and that this association is characterized by a particular topography that may be related to the receptive field organization of somatosensory CNS neurons. Moreover, we propose that the hyperesthetic-hypoesthetic association is dynamically modulated in tandem by pain input.

Quantitative measurement of thromboelastography as a function of platelet count.

T hromboelastography (TEG) analyzes the status of blood coagulation, including abnormalities associated with low platelet count (1). Using TEG to guide platelet transfusion has thus been advocated by several investigators (2–6). However, it is not clear whether TEG variables, assessed from the shape of its tracing, are regulated by platelets quantitatively, because these variables are concurrently under the influence of coagulation factors. We examined the modulation of TEG variables by the amount of platelet, which was controlled by the dilution of platelets into the patient’s plasma without affecting other factors. We also attempted to evaluate the critical platelet counts in coagulation by using this technique.

Spinal orexin-1 receptors mediate anti-hyperalgesic effects of intrathecally-administered orexins in diabetic neuropathic pain model rats

Orexin-A and orexin-B are endogenous ligands of orexin receptors that contain orexin-1 and orexin-2. Activation of the orexinergic system can produce antinociceptive effects in acute inflammatory, mono-neuropathic, and postoperative pain animal models, though the effects of orexins on diabetic neuropathic pain have not been previously investigated. In this study, we studied the anti-hyperalgesic effects of intrathecally administered orexins in a streptozotocin-induced diabetic rat. First, dose-dependent effects were investigated by measuring hind paw withdrawal thresholds in response to noxious-heat and punctate stimuli, after which orexin levels in the cerebrospinal fluid of diabetic rats were measured and compared with those of normal rats using a radioimmunoassay method. The functional role of spinal orexin-1 receptors with the anti-hyperalgesic effects of orexins was also investigated using intrathecal pretreatment with SB-334867, a selective orexin-1 receptor antagonist. Intrathecally administered orexins produced an antinociceptive effect in diabetic rats, however, not in normal rats, though the orexin levels in the cerebrospinal fluid of diabetic rats were similar to those in normal rats. In addition, the anti-hyperalgesic effects of orexins were significantly inhibited by pretreatment with SB-334867. These findings demonstrate that the anti-hyperalgesic effects of orexins in diabetic rats are unlikely due to any direct effect by the supplement on decreased endogenous orexins in the cerebrospinal fluid and that orexin-1 receptors in the spinal cord may be involved in the modulation of nociceptive transmission in diabetic neuropathy. We conclude that the spinal orexinergic system may be a possible target for elucidating the mechanisms of diabetes-induced hyperalgesia.

myofascial Pain in Patients With Postthoracotomy Pain Syndrome

Objective: Postthoracotomy pain syndrome is generally considered to be neuropathic pain due to intercostal nerve injury. However, nonneuropathic pain can also occur following thoracic surgery. We present a series of cases with postthoracotomy pain syndrome in which myofascial pain was thought to be a causative component of postthoracotomy pain syndrome. Case Report: Twenty‐seven patients (17 men and 10 women) were treated with trigger point injections, intercostal nerve blocks, and/or epidural blocks. Clinical criteria were used to diagnose the myofascial pain. A visual analogue scale was used, and sensory disturbances were recorded before and after treatment. A trigger point in a taut muscular band within the scapular region, which we diagnosed as myofascial pain, was observed in 67% of the patients. The existence of this trigger point significantly increased the rate of success for the treatments. Conclusions: Postthoracotomy pain may result, at least in part, from a nonneuropathic origin (myofascial pain). It is recommended that each patient be examined in detail to determine whether there is a trigger point in a taut muscular band within the scapular region. If found, this point is suggested as a good area for anesthetic injection.

Cytosolic Ca2+ movements of endothelial cells exposed to reactive oxygen intermediates: Role of hydroxyl radical-mediated redox alteration of cell-membrane Ca2+ channels

The mode of action of reactive oxygen intermediates in cysosolic Ca2+ movements of cultured porcine aortic endothelial cells exposed to xanthine/xanthine oxidase (X/XO) was investigated. Cytosolic Ca2+ movements provoked by X/XO consisted of an initial Ca2+ release from thapsigargin‐sensitive intracellular Ca2+ stores and a sustained Ca2+ influx through cell‐membrane Ca2+ channels. The Ca2+ movements from both sources were inhibited by catalase, cell‐membrane permeable iron chelators (o‐phenanthroline and deferoxamine), a •OH scavenger (5,5‐dimethyl‐1‐pyrroline‐N‐oxide), or an anion channel blocker (disodium 4, 4′‐diisothiocyano‐2, 2′‐stilbenedisulphonic acid), suggesting that •O2− influx through anion channels was responsible for the Ca2+ movements, in which •OH generation catalyzed by intracellular transition metals (i.e., Haber‐Weiss cycle) was involved. After an initial Ca2+ elevation provoked by X/XO, cytosolic Ca2+ concentration decreased to a level higher than basal levels. Removal of X/XO slightly enhanced the Ca2+ decrease. Extracellular addition of sulphydryl (SH)‐reducing agents, dithiothreitol or glutathione, after the removal of X/XO accelerated the decrement. A Ca2+ channel blocker, Ni2+, abolished the sustained increase in Ca2+, suggesting that Ca2+ influx through cell‐membrane Ca2+ channels was extracellularly regulated by the redox state of SH‐groups. The X/XO‐provoked change in cellular respiration was inhibited by Ni2+ or dithiothreitol as well as inhibitors of Haber‐Weiss cycle, suggesting that Ca2+ influx was responsible for •OH‐mediated cytotoxicity. We concluded that intracellular •OH generation was involved in the Ca2+ movements in endothelial cells exposed to X/XO. Cytosolic Ca2+ elevation was partly responsible for the oxidants‐mediated cytotoxicity.

Effects of pneumoperitoneum on cardiac autonomic nervous activity evaluated by heart rate variability analysis during sevoflurane, isoflurane, or propofol anesthesia.

AbstractBackground: The effects of pneumoperitoneum on the activity of the cardiac autonomic nervous system have not been completely understood. Methods: In this study, 45 unpremedicated adult patients who underwent laparoscopic cholecystectomy were anesthetized with either 3.5% sevoflurane, 2% isoflurane, or 8 mg/kg/h propofol (15 patients in each group). The status of cardiac autonomic nervous activity was evaluated by heart rate variability analysis three times: once when the patient was awake, once after induction of general anesthesia, and once after insufflation for pneumoperitoneum. Intra-abdominal pressure was maintained automatically at 10 mmHg by a carbon dioxide (CO2) insufflator. For each measurement, electrocardiogram was recorded for 256 s and played back offline to detect R-R intervals. Power spectral analysis of heart rate variability was applied, and the low-frequency (LF, 0.04–0.15 Hz) and high-frequency (HF, 0.15–0.40 Hz) bands of the spectral density of the heart rate variability were obtained from a power spectra of R-R intervals using the fast-Fourier transform algorithm. The HF/LF ratio also was analyzed. Results: Measurements of heart rate variability in the three groups showed similar change. Although the power of HF, which represents parasympathetic nervous activity, did not change, the power of LF, which represents both sympathetic and parasympathetic nervous activity, decreased during the anesthetized stage and increased during the insufflated stage. The HF/LF ratio, which represents the balance of parasympathetic and sympathetic activity, increased after induction of general anesthesia, and decreased after insufflation. Conclusions: Our results suggest that pneumoperitoneum increases sympathetic cardiac activity. The choice of general anesthetic did not seem to have a major influence on the change in the cardiac autonomic nervous system after induction of pneumoperitoneum for laparoscopic cholecystectomy.

Effect of etodolac, a COX-2 inhibitor, on neuropathic pain in a rat model

Etodolac, a cyclooxygenase-2 inhibitor, may alleviate nociceptive pain and inhibit the activation of osteoclasts. The aim of the present study was to determine whether etodolac can alleviate heat-evoked hyperalgesia and investigate its possible protective effects on osteoporosis induced by chronic constriction injury (CCI) in rats. A CCI to the sciatic nerve was performed, after which the rats received etodolac orally in a volume of 2 ml at 0, 1, and 10 mg/kg/day for 1 to 5 weeks following surgery (experiment 1); at 0 and 10 mg/kg/day for 1 day to 5 weeks following surgery (experiment 2); and at 0 mg/kg/day for 1 to 5 weeks, 10 mg/kg/day for 1 to 2 weeks after surgery, or 10 mg/kg/day for 1 to 3 weeks after surgery (experiment 3). Paw withdrawal latency after exposure to heat, bone mineral content (BMC) and bone mineral density (BMD) in the whole tibial bone, and the number of tartrate resistant acid phosphate (TRAP)-positive multinucleated osteoclasts were measured. Etodolac alleviated heat-evoked hyperalgesia in the CCI rats and the increase in number of TRAP-positive multinucleated osteoclasts on the CCI-side was abrogated, however, it did not inhibit the decrease of BMC and BMD on the CCI-side. Our results suggest that etodolac is useful for treatment of neuropathic pain.

Safety of the inter-nipple line hand position landmark for chest compression.

BACKGROUND No previous study has investigated the safety of hand position during chest compression determined by the inter-nipple line, in which the heel of one hand is positioned on the centre of the chest between the nipples, from the standpoint of prevention of organ injury. METHODS We measured the distance from the xiphisternal junction to the inter-nipple line (dN) in 1000 surgical patients and the heel length (H) of hands in 100 healthy volunteers, then used the formula H/2-dN to determine the amount of deviation when the heel of the rescuers hand extended to the xiphoid process (D). Next, 100 surgical patients were randomly assigned to 18 anaesthesiologists, who placed the heels of their hands on the sternum for validation. RESULTS The D value was positive in 551 patients, indicating that the heel may extend to the xiphoid process during chest compression in those individuals. Multivariate logistic-regression analyses showed that deviations beyond the xiphoid process to the epigastric region were more likely to occur in female (OR 3.52), elderly (OR 2.00), and short-statured (OR 2.09) patients, and with male rescuers (OR 2.81). During actual positioning, deviation occurred in 51 patients and extended to the epigastric region in 5 females. CONCLUSIONS Simulation of hand position determined by the inter-nipple line resulted in placement of the rescuers hands over the xiphoid process in nearly half of the patients. Hand deviation to the epigastric region may occur when the patient is a short-statured or elderly female, and when the rescuer is male.

Neuropathic pain and prolonged regional inflammation as two distinct symptomatological components in complex regional pain syndrome with patchy osteoporosis : a pilot study

Abstract To reappraise symptomatology of complex regional pain syndrome (CRPS), we investigated the clinical symptoms of seven patients with CRPS who showed associated patchy osteoporosis. The incidence of moderate to severe spontaneous pain, burning pain, mechanical allodynia was higher in patients with significant nerve injury than in those without. Periarticular tenderness adjacent to osteoporotic bones, abnormalities of blood flow, edema and impairment of motor function were seen in both groups of patients. Our clinical observations of patients with CRPS associated with patchy osteoporosis suggest that CRPS may have the following two distinct components: (1) neuropathic pain that includes severe spontaneous pain or severe persistent mechanical allodynia and (2) prolonged regional inflammation, the early phase of which could be indicated by positive inflammatory symptoms of pain (tenderness), heat, redness, swelling and loss of function and their alleviation with corticosteroids.

Reaction between imidazolineoxil N-oxide (carboxy-ptio) and nitric oxide released from cultured endothelial cells: Quantitative measurement of nitric oxide by ESR spectrometry

The performance of 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide for the monitoring agent of nitric oxide was investigated. The agent (125-500 microM) was mixed with equal volume of nitric oxide solution, and aliquots of the mixture were applied to ESR spectroscopy. ESR spectra of 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl, a product of the agent reacted with nitric oxide, were observed. A linear relationship was observed between the amplitude of the signal and concentrations of nitric oxide up to 80 microM. Endothelial cells cultured on microcarriers were packed in a column, perfused with Krebs solutions and the effluent was mixed to the agent. The same ESR spectra were obtained and amplitude of the signal was increased by bradykinin (3-300 nM), decreased by preincubation of NG-monomethyl-L-arginine (3-100 microM) and reversed by following incubation of L-arginine (100 microM).