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1.
Masui ; 64(2): 196-9, 2015 Feb.
Article in Japanese | MEDLINE | ID: mdl-26121817

ABSTRACT

An implantable cardioverter defibrillator (ICD) can falsely recognize noise by monopolar electrocautery as tachyarrhythmia and deliver inappropriate antitachycardia therapy. Application of a clinical magnet on an ICD suspends antitachycardia therapy, but it has not been widely used for this purpose. A 67-year-old male underwent laryngopharyngectomy, cervical esophagectomy, right neck dissection, tracheostomy and reconstruction with free jejunal transplant for recurrent hypopharyngeal cancer. He had an ICD (PARADYM DR8550, Sorin) implanted below the left clavicle for ventricular tachycardia and prolonged QT syndrome. During the operation, a clinical magnet was left on the ICD to disable antitachycardia therapy. The magnet mode of the ICD provided asynchronous AAI pacing at 96 beats x min(-1). The surgery proceeded uneventfully. No episode of ventricular tachyarrythmia or pacing inhibition by electromagnetic interference was observed on electrocardiogram. This case illustrated the potential role of a clinical magnet as an alternative to reprogramming of an ICD by a programmer in the perioperative management of a patient with an ICD when a technical expert to operate a programmer is not available.


Subject(s)
Defibrillators, Implantable , Pharyngeal Neoplasms/surgery , Tachycardia/therapy , Aged , Humans , Magnets , Male , Tachycardia/physiopathology , Tachycardia, Ventricular/physiopathology
2.
Mediators Inflamm ; 2015: 605727, 2015.
Article in English | MEDLINE | ID: mdl-26063975

ABSTRACT

Prostaglandin (PG) E2 and PGI2 are essential to hyperalgesia in inflammatory tissues. These prostaglandins are produced from arachidonic acid, which is cleaved from membrane phospholipids by the action of phospholipase A2 (PLA2). Which isozyme of PLA2 is responsible for the cleavage of arachidonic acid and the production of prostaglandins essential to inflammation-induced hyperalgesia is not clear. In this study, we examined the effects of two PLA2 isozyme-specific inhibitors on carrageenan-induced production of PGE2 and PGI2 in rat hind paw and behavioral nociceptive response to radiant heat. Local administration of bromoenol lactone (BEL), an inhibitor of calcium-independent PLA2 (iPLA2), significantly reduced carrageenan-induced elevation of prostaglandins in the inflamed foot pad 3 h after injection. It also ameliorated the hyperalgesic response between 1 h and 3 h after carrageenan injection. On the other hand, AACOCF3, an inhibitor of cytosolic PLA2, suppressed neither prostaglandin production nor the hyperalgesic response. BEL did not suppress the mRNA levels of iPLA2 ß, iPLA2 γ, cyclooxygenase-2, microsomal prostaglandin E synthase, prostaglandin I synthase, or proinflammatory cytokines in the inflamed foot pad, indicating that BEL did not suppress inflammation itself. These results suggest that iPLA2 is involved in the production of prostaglandins and hyperalgesia at the inflammatory loci.


Subject(s)
Carrageenan/toxicity , Hindlimb/drug effects , Hindlimb/metabolism , Hyperalgesia/chemically induced , Hyperalgesia/drug therapy , Naphthalenes/therapeutic use , Phospholipases A2, Calcium-Independent/antagonists & inhibitors , Pyrones/therapeutic use , Animals , Hindlimb/pathology , Hyperalgesia/metabolism , Male , Prostaglandins/biosynthesis , Rats , Rats, Sprague-Dawley
3.
Cell Mol Neurobiol ; 35(2): 231-41, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25283187

ABSTRACT

Neurotropin (NTP)(®), a non-protein extract isolated from the inflamed skin of rabbits inoculated with vaccinia virus, is used clinically for the treatment of neuropathic pain. Moreover, NTP may activate the descending pain inhibitory system. Depression-like behavior is often complicated by chronic pain. However, little is known about NTP-mediated prevention of mood disorders in chronic pain and its molecular mechanisms. We aimed to investigate the effects of NTP on brain-derived neurotrophic factor (BDNF)-mediated signaling and gene expression in chronic pain. In addition, these effects of NTP were compared with pregabalin which is an anticonvulsant, anxiolytic analgesic used to treat neuropathic pain and fibromyalgia. A chronic constriction injury model was established in Sprague-Dawley rats. The pain response was assessed using a paw withdrawal latency (PWL) test and depression was assessed by the immobility time in a forced swim test (FST). NTP was orally administered in two doses of 50 NU (Neurotropin Unit) and 100 NU/kg for 7 days from day 7 after injury. To measure the analgesic and anti-depressant effects of NTP, either K252a (a tyrosine kinase inhibitor), or 5,7-dihydroxy tryptamine (5,7-DHT, a selective toxin for 5-HTergic neurons) was administered by intracerebroventricular injection. Changes in pERK1/2 and pCREB (immunohistochemistry), 5-HT, and BDNF protein level (ELISA) and BDNF mRNA (RT-PCR) were measured in the anterior cingulate cortex (ACC) and in the rostral ventromedial medulla (RVM) 14 days after injury. After injury, the rats showed a decrease in PWL associated with the increase in time of immobility in FST. In this injury model, NTP blocked both the decrease in PWL and the increase in the FST, while pregabalin (10 mg/kg, po.) did not affect the increase in the FST. These effects of NTP were reversed by K252a, and 5,7-DHT. The analgesic effects of pregabalin were not reversed by K252a. NTP normalized the injury-induced excessive activation of pERK1/2 associated with decreased pCREB and BDNF mRNA in the ACC and in the RVM, and these changes were reversed by 5,7-DHT. In contrast, pregabalin did not affect either pCREB or BDNF levels in the chronic pain model. NTP ameliorated chronic pain and pain-related depression by normalizing the induction of BDNF associated with the 5-HTergic system. Pregabalin showed the analgesic effects but had no effects on either depression or the BDNF pathway. These results suggest that NTP may represent an additional drug strategy for chronic pain associated with depression.


Subject(s)
Brain-Derived Neurotrophic Factor/metabolism , Chronic Pain/drug therapy , Polysaccharides/therapeutic use , Analgesics/pharmacology , Animals , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Brain-Derived Neurotrophic Factor/genetics , Chronic Pain/genetics , Chronic Pain/pathology , Constriction, Pathologic , Cyclic AMP Response Element-Binding Protein/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , Gyrus Cinguli/drug effects , Gyrus Cinguli/metabolism , Male , Phosphorylation/drug effects , Polysaccharides/pharmacology , Protein Kinase Inhibitors/pharmacology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rabbits , Rats, Sprague-Dawley , Serotonergic Neurons/drug effects , Serotonergic Neurons/metabolism , Swimming
4.
Masui ; 63(2): 208-14, 2014 Feb.
Article in Japanese | MEDLINE | ID: mdl-24601122

ABSTRACT

Anesthesia requires informed consent because it is an invasive procedure with high risks. We carried out a questionnaire study in 1,050 patients who were seen at the preoperative evaluation clinic (PAC). Patients who heard about PAC for the first time accounted for 77.9% in spite of having experienced anesthesia. Many patients were provided with the information about anesthesia the day before surgery and medication control and additional checking were difficult to carry out. Some patients (34.2%) were told about anesthesia with no attendant. In particular, about complications of anesthesia, many patients did not remember what the specific explanation had been offered in the past. We thought that it is necessary to explain the complications of anesthesia even if it is the second anesthesia for patients.


Subject(s)
Ambulatory Care Facilities , Anesthesia/adverse effects , Anesthesiology/methods , Knowledge , Patients/psychology , Preoperative Care/methods , Surveys and Questionnaires , Adult , Humans , Patient Education as Topic , Patients/statistics & numerical data , Preoperative Care/statistics & numerical data , Tooth Injuries/etiology , Tooth Injuries/prevention & control
5.
Masui ; 62(7): 784-90, 2013 Jul.
Article in Japanese | MEDLINE | ID: mdl-23905400

ABSTRACT

The purpose of the treatment of chronic non-cancer pain is the improvement of the patient's quality of life, not the complete alleviation of pain. In Japan transdermal fentanyl patch can be used for the treatment of chronic intractable pain including cancer pain and chronic non-cancer pain. In prescribing transdermal fentanyl patch for patients with chronic non-cancer pain, cares should be focused on the selection of the patients and the periodic and continuous observation of analgesic effect and side effects. Patients with mental disorders need the consultation with specialists. In most cases side effects such as nausea, vomiting, constipation and sedation can be well tolerated. However, respiratory suppression or over sedation would also occur and such side effects can sometimes be fatal. Furthermore, long term effects on endocrine and immune systems have not been clarified yet. Proper prescription of opioids during a limited period of time is definitely the primary concern of medical professionals.


Subject(s)
Analgesics, Opioid/administration & dosage , Chronic Pain/drug therapy , Fentanyl/administration & dosage , Pain, Intractable/drug therapy , Humans , Transdermal Patch
6.
Masui ; 61(4): 424-9, 2012 Apr.
Article in Japanese | MEDLINE | ID: mdl-22590951

ABSTRACT

BACKGROUND: The sniffing position, a combination of flexion of the neck and extension of the head, is considered to be suitable for the performance of endotracheal intubation. To place a patient in this position, anesthesiologists usually put a pillow under a patient's occiput. However, with a regular pillow, the resulting extension of the head tends to be suboptimal. METHODS: In an attempt to improve positioning of the head, we started using "a triangular pillow". The name of this pillow comes from its shape in the sagittal section. A patient's head rests on a slope of the pillow so that it assumes an extended position. RESULTS: In this retrospective study, we compared the triangular pillow and the regular pillow employing the laryngoscopic view grade (Cormack grade) and times for tracheal intubation trial. We found that the triangular pillow group showed lower Cormack grades, compared with the regular pillow group. And in the first attempt, the success rate of the triangular pillow group was higher than that of the regular pillow group. CONCLUSIONS: The triangular pillow improves the laryngoscopic view and facilitates endotracheal intubation by optimizing a patient's head position.


Subject(s)
Head , Intubation, Intratracheal/methods , Bedding and Linens , Female , Humans , Intubation, Intratracheal/instrumentation , Laryngoscopy , Male , Middle Aged , Posture , Retrospective Studies
7.
Neurosci Res ; 71(2): 178-82, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21787812

ABSTRACT

Nuclear factor kappa B (NF-κB) is a transcription factor, which is translocated to the nucleus when activated. Herein, we demonstrate immunohistochemically that electrical, chemical, and thermal stimuli, applied to the skin of mice, all induced nuclear translocation and phosphorylation of NF-κB in dorsal root ganglia (DRG) neurons. The latency of this response was short, with effects observable in as little as 3min following stimulation. Few nuclear phospho-NF-κB-positive neurons were observed in DRG innervating unstimulated regions. These results suggest somatosensory stimuli quickly induce NF-κB-mediated gene transcription in DRG, and phospho-NF-κB could be a suitable histological marker for activated DRG neurons.


Subject(s)
Cell Nucleus/metabolism , Ganglia, Spinal/metabolism , Hot Temperature , NF-kappa B/metabolism , Sensory Receptor Cells/metabolism , Active Transport, Cell Nucleus/physiology , Animals , Electric Stimulation/methods , Hot Temperature/adverse effects , Male , Mice , Mice, Inbred C57BL , Phosphorylation/physiology , Stimulation, Chemical , Transcription, Genetic/physiology
8.
J Anesth ; 24(4): 643-5, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20386934

ABSTRACT

We constructed an on-line data management system and linked it to the communication protocol of a portable blood analyzer (i-STAT) in each operating room of our institution. We developed a new program that integrates circulatory dynamics data from a monitor with laboratory data from the i-STAT. Our new program permits the results to be viewed through an intranet using a novel prototype communication device for the i-STAT 300F. We verified that this system can improve the quality of patient care both bedside and in the monitoring room and compared the costs of blood testing using a conventional desktop blood-gas analyzer and using the i-STAT. We found that the novel integration of circulatory dynamics with laboratory data enhanced the quality of intraoperative patient monitoring and reduced the cost and work load of doctors working in the operating room.


Subject(s)
Electronic Data Processing , Hematologic Tests/instrumentation , Humans , Monitoring, Intraoperative , Quality of Health Care
9.
Masui ; 55(4): 464-7, 2006 Apr.
Article in Japanese | MEDLINE | ID: mdl-16634553

ABSTRACT

A case of airway obstruction caused by the tongue swelling is reported. The patient is a 5-year-old boy scheduled for bilateral tonsillectomy for sleep apnea syndrome. Anesthesia was slowly induced by sevoflurane and maintained with nitrous oxide, fentanyl and sevoflurane. Bilateral tonsillectomy and adenoidectomy were performed uneventfully under general anesthesia. The operation time was 2 hours and 30 minutes. Following the surgical procedure, the endotracheal tube was removed. Shortly after the extubation, the patient complained of difficult articulation and paradoxical respiration. Trachea was intubated immediately. Oxygen saturation was within normal limits throughout all the procedures. Swelling of the tongue was aggravated and was not relieved by steroid infusion. Massive swelling of the face and neck was observed on the next day. CT scan and fiberoptic scope examination showed the swollen tongue obstructing the upper airway. Additional administration of steroid was continued. On the third postoperative day, edema was relieved and the endotracheal tube was removed. Clinical course after the extubation was uneventful. No laboratory data was obtained suggesting the allergic basis. Extubation should be performed carefully and respiratory condition should be observed cautiously following the oral surgery of even a short duration.


Subject(s)
Adenoidectomy , Airway Obstruction/etiology , Sleep Apnea Syndromes/surgery , Tongue/pathology , Tonsillectomy , Anesthesia, General/methods , Child, Preschool , Humans , Male
10.
Masui ; 54(11): 1302-5, 2005 Nov.
Article in Japanese | MEDLINE | ID: mdl-16296376

ABSTRACT

We gave anesthesia to a neonate with a retroperitoneal giant teratoma who underwent its extirpation. Even if patients have a prenatal diagnosis of teratoma like this case, there are many patients, especially infants, with severe general condition. We report the difficulty for management during anesthesia because of severe respiratory acidosis due to pressure from diaphragmatic pleura by tumor, severe circulatory disorder due to massive bleeding during operation and severe hyperkalemia due to renal failure.


Subject(s)
Anesthesia, General/methods , Perioperative Care , Retroperitoneal Neoplasms/surgery , Teratoma/surgery , Acidosis, Respiratory/complications , Female , Humans , Hyperkalemia/complications , Infant , Retroperitoneal Neoplasms/complications , Teratoma/complications
11.
Crit Care Med ; 32(3): 795-800, 2004 Mar.
Article in English | MEDLINE | ID: mdl-15090964

ABSTRACT

OBJECTIVES: To examine whether peripheral burn injury in rats elevates prostaglandin E2 in the central nervous system and to determine where in the central nervous system enzymes responsible for prostaglandin E2 synthesis are expressed. DESIGN: Prospective controlled animal study. SETTING: University research laboratory. SUBJECTS: Sprague-Dawley rats. INTERVENTIONS: Rats received either approximately 25% full-thickness burn injury or sham treatment. At 36 hrs after the injury, the cerebrospinal fluid was sampled to measure prostaglandin E2, and the brain and the spinal cord were sampled for immunohistochemical detection of cyclooxygenase-2 and microsomal-type prostaglandin E2 synthase, enzymes that are responsible for prostaglandin E2 production. MEASUREMENTS AND MAIN RESULTS: The prostaglandin E2 concentration in the cerebrospinal fluid was significantly elevated in the injured rats, and this elevation was suppressed by a cyclooxygenase-2-specific inhibitor, NS398. Only in the injured rats, cyclooxygenase-2 and microsomal-type prostaglandin E synthase proteins were detected in vascular endothelial cells throughout the central nervous system with no regional difference. A double-immunofluorescence study revealed that cyclooxygenase-2 and microsomal-type prostaglandin E synthase were coexpressed in the perinuclear region of the endothelial cells. CONCLUSIONS: These results indicate that peripheral burn injury induces cyclooxygenase-2 and microsomal-type prostaglandin E synthase in endothelial cells of the central nervous system. These enzymes likely elevate the cerebrospinal fluid concentration of prostaglandin E2, a prostanoid that, in turn, activates prostaglandin E2 receptors on the central nervous system neurons involved in the general symptoms following burn injury.


Subject(s)
Brain/metabolism , Burns/metabolism , Dinoprostone/biosynthesis , Endothelium, Vascular/metabolism , Intramolecular Oxidoreductases/metabolism , Isoenzymes/metabolism , Prostaglandin-Endoperoxide Synthases/metabolism , Acute-Phase Reaction/physiopathology , Animals , Brain/cytology , Burns/enzymology , Cyclooxygenase 2 , Endothelium, Vascular/cytology , Male , Prospective Studies , Prostaglandin-E Synthases , Rats , Rats, Sprague-Dawley , Statistics, Nonparametric
12.
Biol Pharm Bull ; 26(8): 1178-80, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12913272

ABSTRACT

We have examined the effects of intrathecal (i.t.) injection of the muscarinic acetylcholine receptor antagonist atropine on the clonidine-induced nociceptive effect in formalin-induced nociception in rats. The injection of 5% formalin into the hind paw caused biphasic nociceptive responses, and i.t. injection of clonidine inhibited both phases of the nociceptive response in a dose-dependent manner. Pretreatment with atropine (i.t.) only partially inhibited the nociceptive effect of clonidine. These results suggest that the nociceptive effect of clonidine in the rat formalin model may be at least partly mediated by muscarinic acetylcholine receptors in the spinal cord.


Subject(s)
Analgesics/pharmacology , Clonidine/pharmacology , Pain Measurement/drug effects , Receptors, Muscarinic/physiology , Animals , Dose-Response Relationship, Drug , Male , Pain Measurement/methods , Rats , Rats, Wistar , Spinal Cord
13.
J Neurochem ; 86(2): 318-28, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12871573

ABSTRACT

Inflammation is often accompanied with hyperalgesia. This hyperalgesia is mediated partly by prostaglandin(s) produced in the CNS through the cyclooxygenase-2 (COX-2) dependent pathway. However, it remains unclear where COX-2 is induced in the CNS during inflammation, and how it is involved in hyperalgesia. We studied the precise site of COX-2 induction in the CNS, the relation between the time course of COX-2 induction and that of hyperalgesia, and the effect of COX-2-selective inhibitor by using a carrageenan model. Carrageenan injection induced expression of COX-2-like immunoreactivity in vascular endothelial cells throughout the CNS. This response became evident by 3 h, and was most prominent at 6 h after carrageenan injection. This COX-2 induction was associated with an elevation of prostaglandin E2 in the cerebrospinal fluid, being evident at 3 h, larger at 6 h, and alleviated by a COX-2-selective inhibitor. Thermal hyperalgesia became evident at 1 h, further increased thereafter, and remained elevated until 6 h. Intrathecal administration of COX-2-selective inhibitor 2 h after the carrageenan injection exerted a prominent therapeutic effect on hyperalgesia. These results demonstrate that, during carrageenan-induced inflammation, endothelial cells are the major source of prostaglandin(s) in the CNS, and this endothelial expression of COX-2 is involved in the inflammation-induced hyperalgesia.


Subject(s)
Central Nervous System/physiopathology , Endothelium, Vascular/enzymology , Hyperalgesia/physiopathology , Inflammation , Isoenzymes/metabolism , Prostaglandin-Endoperoxide Synthases/metabolism , Animals , Brain/blood supply , Brain/pathology , Brain/physiopathology , Carrageenan , Central Nervous System/blood supply , Central Nervous System/pathology , Cyclooxygenase 2 , Cyclooxygenase 2 Inhibitors , Cyclooxygenase Inhibitors/pharmacology , Dinoprostone/cerebrospinal fluid , Disease Models, Animal , Endothelium, Vascular/drug effects , Endothelium, Vascular/pathology , Enzyme Induction/drug effects , Hindlimb/drug effects , Hindlimb/physiopathology , Hyperalgesia/etiology , Hyperalgesia/pathology , Immunohistochemistry , Inflammation/chemically induced , Inflammation/complications , Isoenzymes/antagonists & inhibitors , Male , Nitrobenzenes/pharmacology , Pain Measurement , Rats , Rats, Sprague-Dawley , Spinal Cord/blood supply , Spinal Cord/pathology , Spinal Cord/physiopathology , Sulfonamides/pharmacology
14.
Masui ; 52(1): 64-6, 2003 Jan.
Article in Japanese | MEDLINE | ID: mdl-12632624

ABSTRACT

In recent years, the use of laparoscopic techniques for surgical operations has been increasing, because this procedure is less invasive and is excellent in regard to patient's quality of life. Normally, complications are rare in laparoscopic surgery. However, we experienced a case of pulmonary embolism and one case of ileus as complications after laparoscopic radical prostatectomy. Especially, in this type of operation, the danger of complications is increased due to the severe head down and lithotomy position, which is employed to ensure a good view during operation. In this particular case, the long duration of operation may have been another related risk factor. There were no risk factors for pulmonary embolism such as those encountered when a patient is aged, obese, or bed ridden for a long time. However, an intermittent air massage must be applied to the lower legs to prevent thrombus due to poor blood circulation of the lower extremities below the knee during the surgery. It is also necessary to change the posture of the patient frequently after the operation. In addition, the administration of low molecular weight heparin may also be effective.


Subject(s)
Intestinal Obstruction/therapy , Laparoscopy , Postoperative Complications/therapy , Prostatectomy , Pulmonary Embolism/therapy , Aged , Anesthesia, General , Heparin, Low-Molecular-Weight/administration & dosage , Humans , Intestinal Obstruction/prevention & control , Male , Massage , Posture , Pulmonary Embolism/prevention & control
15.
J Clin Anesth ; 15(1): 1-8, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12657403

ABSTRACT

STUDY OBJECTIVE: To observe changes in the peripheral lymphocyte subpopulations as an index of cellular immunity during neurosurgical procedures. DESIGN: Clinical study. SETTING: Operating room of a university hospital. PATIENTS: 11 patients with early intracranial disease who were scheduled to undergo elective neurosurgery with general anesthesia. Patients in the control group (n = 10) underwent minor surgeries such as ophthalmologic, otorhinolaryngological, or orthopedic surgeries. INTERVENTIONS: Blood was sampled before anesthesia induction (t0) for baseline and at 1 hour (t(1)) and 2 hours (t(2)) following surgical incision. MEASUREMENTS: Detection and quantification of lymphocyte subpopulations were performed at each time point using single-label and double-label analyses of monoclonal antibodies against lymphocyte membrane surface markers. MAIN RESULTS: Significant changes in patients who underwent a neurosurgical procedure included: the percentage of total T cells (CD3+) from 57.54 +/- 3.50% at t(0) to 51.41 +/- 4.26% at t(1) and 46.29 +/- 4.02% at t(2); the percentage of inducer T cells (CD4+, Leu8+) from 27.39 +/- 2.26% at t(0), to 23.26 +/- 2.30% at t(1) and 20.82 +/- 2.70% at t(2); the CD4/CD8 ratio, from 1.78 +/- 0.25% at t(0) to 1.35 +/- 0.12% at t(1) and 1.22 +/- 0.17% at t(2). The percentage of suppressor T cells (CD8+, Leu15+) increased significantly from 10.8 +/- 1.07% at t(0) to 13.64 +/- 1.62% at t(1), and 14.82 +/- 1.24% at t(2). The percentages of the natural killer cell subsets also increased significantly. Control group patients who underwent minor surgeries showed no significant changes. CONCLUSIONS: Neurosurgery-induced significant suppression of cellular immunity was demonstrated in peripheral lymphocyte subpopulations, probably from the surgical stress on the central nervous system.


Subject(s)
Lymphocytes/physiology , Neurosurgical Procedures/adverse effects , Stress, Physiological/immunology , Anesthesia, General , Antibodies, Monoclonal , CD3 Complex/drug effects , CD4 Lymphocyte Count , CD4-CD8 Ratio , Female , Flow Cytometry , Humans , Immunity, Cellular/immunology , Killer Cells, Natural , Lymphocyte Count , Lymphocytes/immunology , Male , Middle Aged , Receptors, Cell Surface/drug effects , T-Lymphocytes, Regulatory
16.
Br J Pharmacol ; 138(4): 689-97, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12598423

ABSTRACT

1. We used spinal microdialysis in awake rats to investigate whether the repeated withdrawal with naloxone during continuous spinal infusion of morphine would lead to a progressively greater spinal glutamate release and a more pronounced intrathecal tolerance. 2. Rats received lumbar intrathecal (IT) infusion of morphine (IT-M: 20 nmol microl(-1) h(-1)) or saline (IT-S: 1 microl h(-1)) continuously for 3 days. Both groups were further subdivided to receive intraperitoneal (i.p.) injection of naloxone (IP-N: 0.6 mg kg(-1)) or saline (IP-S: 3 ml kg(-1)) every 24 h after the beginning of IT infusion. Daily thermal escape latencies, withdrawal signs, the resting basal release of spinal amino acids before IP injection and the release immediately after the injection (evoked) were measured. 3. Rats receiving IT morphine showed a maximum increase in thermal escape latency on day 1, after which this value declined, with the fastest decline observed in IT morphine + IP naloxone group. On day 1, no significant difference was observed among groups in the resting basal release of amino acids. Rats in IT morphine + i.p. naloxone group displayed a progressive increase in this value. The release was not significantly altered in other groups. 4. For the IT-M + IP-N group, basal resting dialysate concentrations of Glu, Asp and Tau rose steadily over the 3-day infusion interval. No change in basal resting release was noted for any other treatment. 5. Evoked release (after i.p. naloxone) in IT-M animals displayed a progressive increase over the three repeated exposures. Evoked release did not change significantly in other treatment groups. 6. The degree of precipitated withdrawal significantly correlated with the increase in glutamate acutely evoked by i.p. injection. 7. The present results show that periodic transient withdrawal of spinal opiate agonist activity leads to a progressive increase in glutamate outflow and withdrawal signs, in a manner consistent with an enhanced development of spinal tolerance.


Subject(s)
Amino Acids/metabolism , Drug Tolerance/physiology , Morphine/pharmacology , Spinal Cord/metabolism , Substance Withdrawal Syndrome/metabolism , Animals , Male , Morphine/therapeutic use , Pain Measurement/drug effects , Pain Measurement/methods , Rats , Rats, Sprague-Dawley , Spinal Cord/drug effects
17.
Neurosci Lett ; 328(2): 97-100, 2002 Aug 09.
Article in English | MEDLINE | ID: mdl-12133564

ABSTRACT

Acute burn injury is usually associated with pain in the injured and nearby areas. However, we have recently reported that a thoracic scald induces hindpaw hyperalgesia during the healing stage in rats. The present study investigated the cause of the remotely occurring hyperalgesia. Behavioral testing using the von Frey test revealed that rats developed hyperalgesia in the neck and flank as well as the hindpaw 2-3 weeks after injury. The concentration of nerve growth factor (NGF) in the skin of the chest increased markedly during the healing stage. Moreover, rats injected daily with anti-NGF serum after burn injury did not develop hyperalgesia, suggesting that increased NGF in the tissue of the healing skin is a key factor causing systemic hyperalgesia during the recovery stage.


Subject(s)
Burns/complications , Hyperalgesia/etiology , Mechanoreceptors/metabolism , Nerve Growth Factor/metabolism , Nociceptors/metabolism , Peripheral Nerves/metabolism , Skin/injuries , Acute Disease , Animals , Antibodies/pharmacology , Burns/metabolism , Burns/physiopathology , Foot/innervation , Foot/physiopathology , Hyperalgesia/metabolism , Hyperalgesia/physiopathology , Male , Mechanoreceptors/drug effects , Nerve Growth Factor/antagonists & inhibitors , Neurons, Afferent/drug effects , Neurons, Afferent/metabolism , Nociceptors/drug effects , Pain Measurement , Pain Threshold/drug effects , Pain Threshold/physiology , Peripheral Nerves/drug effects , Peripheral Nerves/physiopathology , Physical Stimulation , Rats , Rats, Sprague-Dawley , Skin/physiopathology , Thorax
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