Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 41
Filter
1.
ACS Chem Neurosci ; 9(7): 1566-1571, 2018 07 18.
Article in English | MEDLINE | ID: mdl-29660270

ABSTRACT

Several chemotherapeutic agents used for cancer treatment induce dose-limiting peripheral neuropathy that compromises patients' quality of life and limits cancer treatment. Recently, mitochondrial dysfunction has been shown to be involved in the mechanism of chemotherapy-induced peripheral neuropathy. SS-20 is a mitochondria-targeted peptide that promotes mitochondrial respiration and restores mitochondrial bioenergetics. In the present study, we examined the protective effect of SS-20 against the development of chemotherapy-induced peripheral neuropathy utilizing a murine model of peripheral neuropathy induced by oxaliplatin, a first-line chemotherapy agent for colon cancer. Weekly administrations of oxaliplatin induced peripheral neuropathy as demonstrated by the development of neuropathic pain and loss of intraepidermal nerve fibers in the hind paw. Continuous administration of SS-20 protected against the development of oxaliplatin-induced neuropathic pain and mitigated the loss of intraepidermal nerve fibers to normal levels. Our findings suggest that SS-20 may be a drug candidate for the prevention of chemotherapy-induced peripheral neuropathy.


Subject(s)
Antineoplastic Agents/adverse effects , Mitochondria/drug effects , Oligopeptides/pharmacology , Oxaliplatin/adverse effects , Peripheral Nervous System Diseases/drug therapy , Protective Agents/pharmacology , Animals , Disease Models, Animal , Hyperalgesia/drug therapy , Hyperalgesia/etiology , Hyperalgesia/metabolism , Hyperalgesia/pathology , Male , Mice, Inbred BALB C , Mitochondria/metabolism , Molecular Structure , Neuralgia/drug therapy , Neuralgia/etiology , Neuralgia/metabolism , Neuralgia/pathology , Oligopeptides/chemistry , Peripheral Nerves/drug effects , Peripheral Nerves/metabolism , Peripheral Nerves/pathology , Peripheral Nervous System Diseases/etiology , Peripheral Nervous System Diseases/metabolism , Peripheral Nervous System Diseases/pathology , Protective Agents/chemistry
2.
Anesthesiology ; 128(5): 992-1003, 2018 05.
Article in English | MEDLINE | ID: mdl-29521652

ABSTRACT

BACKGROUND: Sleepiness and decrease in attention are dose-limiting side effects of opioids. The orexin/hypocretin system plays an important role in maintaining wakefulness. This study aimed to explore the potential of a nonpeptide orexin receptor agonist to alleviate morphine-induced sedative effects. METHODS: Morphine sedative effects were evaluated as changes in electroencephalogram (EEG), locomotor activity, and acoustic startle response in rats (n = 5 to 9 per group). Effects of intracerebroventricular orexin-A and systemic orexin type-2 receptor agonist, YNT-185, on EEG changes induced by morphine were examined. Furthermore, the authors examined effects of morphine administered with or without YNT-185 on locomotor activity and on acoustic startle response. RESULTS: Morphine-induced, frequent, short epochs of increased power (total epoch duration: 0.5 [0.0 to 8.0] s/10 min during baseline vs. 74.0 [49.0 to 115.0] s/10 min during the post-morphine administration period; P = 0.012). EEG analyses revealed that morphine-induced, high-amplitude, slow activity (increase in spectral power of frequencies less than 15 Hz, baseline vs. postmorphine; P < 0.001). Orexin-A and YNT-185 attenuated these changes. Locomotor activity decreased after morphine (268 [103 to 889] ambulatory movement counts during baseline period [20 min] vs. 138 [7 to 434] counts during 40 to 59 min postadministration; P = 0.012), but did not change after morphine with YNT-185 (363 [121 to 636] vs. 864 [381 to 1092] counts, difference within morphine + YNT-185 group; P = 0.071). Startle response latency was longer after morphine (26 [20 to 28] ms) than after morphine with YNT-185 (17 [16 to 18] ms; P = 0.012). CONCLUSIONS: Orexin-A and/or YNT-185 attenuated morphine-induced sedative effects assessed by EEG changes and behavioral measures in rats. The authors' results suggest that orexin-2 receptor activation alleviates morphine-induced sedative effects.


Subject(s)
Morphine/pharmacology , Orexin Receptors/agonists , Aniline Compounds/pharmacology , Animals , Benzamides/pharmacology , Dose-Response Relationship, Drug , Electroencephalography/drug effects , Hypnotics and Sedatives/pharmacology , Male , Morphine/adverse effects , Motor Activity/drug effects , Orexin Receptors/physiology , Orexins/pharmacology , Rats , Rats, Sprague-Dawley , Reflex, Startle/drug effects , Respiration/drug effects
3.
Neuropeptides ; 61: 95-100, 2017 Feb.
Article in English | MEDLINE | ID: mdl-28041630

ABSTRACT

Orexins are neuropeptides that are localized to neurons in the lateral and dorsal hypothalamus but its receptors are distributed to many different regions of the central nervous system. Orexins are implicated in a variety of physiological functions including sleep regulation, energy homeostats, and stress reactions. Furthermore, orexins administered exogenously have been shown to have analgesic effects in animal models. A type of intractable pain in patients is pain due to chemotherapy-induced peripheral neuropathy (CIPN). Several chemotherapeutic agents used for the treatment of malignant diseases induce dose-limiting neuropathic pain that compromises patients' quality of life. Here, we examined the analgesic effect of orexin-A in a murine model of CIPN, and compared it with the effect of duloxetine, the only drug recommended for the treatment of CIPN pain in patients. CIPN was induced in male BALB/c mice by repeated intraperitoneal injection of oxaliplatin, a platinum chemotherapeutic agent used for the treatment of advanced colorectal cancer. Neuropathic mechanical allodynia was assessed by the von Frey test, and the effect on acute thermal pain was assessed by the tail flick test. Intracerebroventricularly administered orexin-A dose-dependently attenuated oxaliplatin-induced mechanical allodynia and increased tail flick latencies. Oxaliplatin-induced mechanical allodynia was completely reversed by orexin-A at a low dose that did not increase tail flick latency. Duloxetine only partially reversed mechanical allodynia and had no effect on tail flick latency. The analgesic effect of orexin-A on oxaliplatin-induced mechanical allodynia was completely antagonized by prior intraperitoneal injection of SB-408124 (orexin type-1 receptor antagonist), but not by prior intraperitoneal injection of TCS-OX2-29 (orexin type-2 receptor antagonist). Our findings suggest that orexin-A is more potent than duloxetine in relieving pain CIPN pain and its analgesic effect is mediated by orexin type-1 receptors. Orexin type-1 receptor agonists may have potential therapeutic roles in the treatment of CIPN pain in patients.


Subject(s)
Analgesics/therapeutic use , Hyperalgesia/drug therapy , Neuralgia/drug therapy , Orexins/therapeutic use , Analgesics/pharmacology , Animals , Antineoplastic Agents , Hyperalgesia/chemically induced , Mice , Neuralgia/chemically induced , Orexins/pharmacology , Organoplatinum Compounds , Oxaliplatin , Pain Measurement
4.
Int J Clin Oncol ; 21(1): 1-12, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26081252

ABSTRACT

The purpose of this article is to disseminate the standard of antiemetic therapy for Japanese clinical oncologists. On the basis of the Appraisal of Guidelines for Research and Evaluation II instrument, which reflects evidence-based clinical practice guidelines, a working group of the Japanese Society of Clinical Oncology (JSCO) reviewed clinical practice guidelines for antiemesis and performed a systematic review of evidence-based domestic practice guidelines for antiemetic therapy in Japan. In addition, because health-insurance systems in Japan are different from those in other countries, a consensus was reached regarding standard treatments for chemotherapy that induce nausea and vomiting. Current evidence was collected by use of MEDLINE, from materials from meetings of the American Society of Clinical Oncology National Comprehensive Cancer Network, and from European Society of Medical Oncology/Multinational Association of Supportive Care in Cancer guidelines for antiemesis. Initially, 21 clinical questions (CQ) were selected on the basis of CQs from other guidelines. Patients treated with highly emetic agents should receive a serotonin (5-hydroxytryptamine; 5HT3) receptor antagonist, dexamethasone, and a neurokinin 1 receptor antagonist. For patients with moderate emetic risk, 5HT3 receptor antagonists and dexamethasone were recommended, whereas for those receiving chemotherapy with low emetic risk dexamethasone only is recommended. Patients receiving high-emetic-risk radiation therapy should also receive a 5HT3 receptor antagonist. In this paper the 2010 JSCO clinical practice guidelines for antiemesis are presented in English; they reveal high concordance of Japanese medical circumstances with other antiemetic guidelines that are similarly based on evidence.


Subject(s)
Antiemetics/therapeutic use , Antineoplastic Agents/adverse effects , Medical Oncology , Nausea/chemically induced , Practice Guidelines as Topic , Vomiting/chemically induced , Dexamethasone/therapeutic use , Humans , Japan , Nausea/drug therapy , Serotonin 5-HT3 Receptor Antagonists/therapeutic use , Societies, Medical , Time Factors , Vomiting/drug therapy
5.
Masui ; 65(11): 1112-1118, 2016 Nov.
Article in Japanese | MEDLINE | ID: mdl-30351799

ABSTRACT

Recently in Japan, more patients are receiving chronic opioid therapy for cancer pain or chronic pain, and there is an increasing number of such patients presenting for surgery. The anesthesiologist should be familiar with available opioid formulations as well as the change they induce by their chronic administra- tion, such as physical dependence, opioid tolerance and opioid-induced hyperalgesia. Physical dependence results in withdrawal symptoms when the opioid is abruptly interrupted or when the dosage is markedly reduced in a short period of time. Furthermore, these patients tend to have increased pain and increased opioid requirements postoperatively, most likely due to opioid tolerance and opioid-induced hyperalgesia. Peri- operative management of these patients require knowledge and skills to manage these phenomena.


Subject(s)
Analgesics, Opioid/therapeutic use , Perioperative Care , Chronic Pain/drug therapy , Humans , Hyperalgesia , Japan , Pain Management/methods
6.
Masui ; 64(11): 1160-5, 2015 Nov.
Article in Japanese | MEDLINE | ID: mdl-26689067

ABSTRACT

One of the key issues in the treatment of pain is to choose the appropriate route and dosage form of analgesics for each individual patient in pain. New drug forms of fentanyl absorbed by oral or nasal mucosa, and buprenorphine absorbed by rectal mucosa are described in this chapter. Only lipophilic opioids such as fentanyl and buprenorphine can be absorbed via the mucosa of oral or nasal cavity of the human body. The T max of rapid onset opioids (ROO) such as fentanyl buccal or sublingual tablets is the fastest among various dosage forms of opioid analgesics. However, such rapid increase in plasma concentration of fentanyl by ROO formulations may cause the risk of respiratory depression. Safe ways to use ROO analgesics are described.


Subject(s)
Analgesics, Opioid/administration & dosage , Buprenorphine/administration & dosage , Nasal Mucosa/metabolism , Administration, Mucosal , Administration, Oral , Analgesics, Opioid/therapeutic use , Buprenorphine/therapeutic use , Fentanyl/administration & dosage , Humans , Pain/drug therapy , Rectal Absorption
7.
Jpn J Clin Oncol ; 45(2): 189-96, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25378647

ABSTRACT

OBJECTIVE: A randomized, crossover, double-blinded placebo-controlled and non-blinded active drug-controlled, comparative clinical trial was conducted to evaluate the efficacy and safety of sublingual fentanyl tablet. METHODS: Subjects were patients treated with strong opioids at fixed intervals for chronic cancer pain and with oral morphine as rescue medication for breakthrough pain. Sublingual fentanyl was administered at doses that were 1/25th (high dose) and 1/50th (low dose) of the dose of rescue morphine and was compared with placebo and oral morphine. The primary endpoint was pain intensity difference at 30 min after administration. (Clinical Trials Government; NCT00684632). RESULTS: Fifty-one patients were enrolled in the investigation. Their mean pain intensity in visual analog scale before rescue medication prior to the investigation was 60.96 (16.44, standard deviation) mm. Compared with placebo, the low and high doses of sublingual fentanyl showed significant analgesic effects (least squares mean difference, 4.54 and 8.49 mm; P = 0.014, P < 0.001, respectively). Adverse reactions were observed in 17.6%, the most common being constipation, nausea and somnolence. The incidence of adverse reactions during the high-dose administration period was higher than that during the low-dose and active control drug administration periods. CONCLUSIONS: Patients treated with strong opioid analgesics at fixed intervals for chronic cancer pain and with oral morphine at doses up to 20 mg as rescue medication were investigated. The doses of sublingual fentanyl to treat breakthrough pain were determined from rescue morphine doses by use of conversion ratios. In these patients, administration of sublingual fentanyl at doses determined by a conversion ratio of 1/50 was effective and safe. Further studies are needed to validate the use of this conversion method.


Subject(s)
Analgesics, Opioid/administration & dosage , Breakthrough Pain/drug therapy , Breakthrough Pain/etiology , Fentanyl/administration & dosage , Morphine/administration & dosage , Neoplasms/complications , Administration, Oral , Administration, Sublingual , Adult , Aged , Chronic Pain/drug therapy , Chronic Pain/etiology , Cross-Over Studies , Double-Blind Method , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Pain Measurement , Patient Selection , Severity of Illness Index , Tablets , Treatment Outcome
8.
Int J Clin Oncol ; 20(1): 198-206, 2015 Feb.
Article in English | MEDLINE | ID: mdl-24839047

ABSTRACT

BACKGROUND: Breakthrough cancer pain typically has a rapid onset and relatively short duration. Due to this temporal profile, it may not be adequately relieved by oral opioid analgesics. The sublingual fentanyl orally disintegrating tablet is a formulation by which fentanyl can be rapidly absorbed across the oral mucosa producing rapid-onset analgesia, and which may be effective for breakthrough pain treatment. METHODS: A multicenter, randomized, placebo-controlled, double-blind comparative study was conducted to evaluate the efficacy and safety of the sublingual fentanyl tablet at optimized doses for breakthrough pain treatment in cancer patients treated with strong opioid analgesics at fixed intervals. The optimal dose was determined by open-label dose titration. The efficacy and safety of a 12-week extended treatment were also evaluated. RESULTS: Eleven of 42 subjects who received the sublingual fentanyl tablet experienced adverse drug reactions. Common reactions were somnolence, constipation, nausea, and vomiting. No serious adverse reactions occurred. Sublingual fentanyl tablets at optimal doses and placebo were administered to 37 subjects in a double-blinded manner. A significant analgesic effect of the sublingual fentanyl tablet was present compared to placebo at 30 min after administration. The sublingual fentanyl tablet was also effective and safe during extended treatment, in which changes in basal opioid doses as well as sublingual fentanyl tablet doses were made as needed. CONCLUSION: Sublingual fentanyl tablets at doses determined by titration were effective and safe for breakthrough pain treatment in cancer patients treated with strong opioid analgesics at fixed intervals. Extended treatment up to 12 weeks was also effective and safe.


Subject(s)
Analgesics, Opioid/administration & dosage , Breakthrough Pain/drug therapy , Breakthrough Pain/etiology , Fentanyl/administration & dosage , Neoplasms/complications , Tablets/administration & dosage , Administration, Sublingual , Adult , Aged , Aged, 80 and over , Double-Blind Method , Female , Humans , Male , Middle Aged , Pain Measurement/methods , Time Factors , Treatment Outcome
9.
Anesthesiology ; 120(2): 459-73, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24064792

ABSTRACT

BACKGROUND: Oxaliplatin, a chemotherapeutic agent used for the treatment of colorectal cancer, induces dose-limiting neuropathy that compromises quality of life. This study aimed to reproduce, in mice, patients' symptoms of oxaliplatin-induced neuropathy and to observe effects of SS-31, a mitochondria-targeted antioxidant on the neuropathy. METHODS: Neuropathy was induced by single or repeated injections of oxaliplatin. Cold and mechanical hypersensitivities were assessed by 15°C-cold plate, temperature preference, and von Frey tests. Morphology of peripheral nerves and dorsal root ganglions, expression of spinal cord c-Fos, density of intraepidermal nerve fibers, and levels of dorsal root ganglion-reactive oxygen/nitrogen species were examined. SS-31 was administered concomitantly or after oxaliplatin injections. RESULTS: Single injection of oxaliplatin induced cold hypersensitivity in forepaws but not in hind paws which resolved within days (maximal forepaw shakes: 28 ± 1.5 vs. 9.3 ± 1.6/150 s, mean ± SEM, P < 0.001, n = 6 per group). Oxaliplatin-administered mice disfavored 10° and 15°C plates more than control. Paw stimulation at 15°C induced c-Fos-positive cells within superficial laminae of the dorsal horn in C7-T1 segments. Weekly administrations induced gradual development of persistent mechanical allodynia in the hind paws (minimal mechanical threshold: 0.19 ± 0.08 vs. 0.93 ± 0.11 g, P < 0.001, n = 10 per group). Microscopy revealed no overt morphological changes in peripheral nerves and dorsal root ganglions. Concomitant SS-31 administration with repeated oxaliplatin administration attenuated both cold and mechanical hypersensitivity. Decrease in intraepidermal nerve fibers and increase in dorsal root ganglion-reactive oxygen/nitrogen species were also attenuated. Acute SS-31 administration after symptoms were established reversed only cold hypersensitivity. CONCLUSION: This model of oxaliplatin-induced neuropathy mimicked patients' conditions. SS-31 has potentials to prevent both acute and chronic neuropathies but is only helpful in treatment of acute neuropathy. (Anesthesiology 2014; 120:459-73).


Subject(s)
Antineoplastic Agents/toxicity , Antioxidants/therapeutic use , Mitochondria/drug effects , Organoplatinum Compounds/toxicity , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/drug therapy , Animals , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Chronic Disease , Cold Temperature , Ganglia, Spinal/drug effects , Immunohistochemistry , Mice , Mice, Inbred BALB C , Mice, SCID , Neoplasm Transplantation , Organoplatinum Compounds/pharmacology , Oxaliplatin , Pain Measurement , Pain Threshold/drug effects , Physical Stimulation , Posterior Horn Cells/drug effects , Posterior Horn Cells/metabolism , Proto-Oncogene Proteins c-fos/biosynthesis , Reactive Nitrogen Species/metabolism , Reactive Oxygen Species/metabolism
10.
Breast Cancer ; 21(2): 191-7, 2014 Mar.
Article in English | MEDLINE | ID: mdl-22644872

ABSTRACT

BACKGROUND: Post-mastectomy pain syndrome (PMPS) is chronic pain after breast cancer surgery and is reported to influence quality of life (QOL). Although the results of a survey in Japan showed high incidence, at 21-65 %, many of the patients had never been treated for PMPS. One reason for this low treatment rate may be poor understanding of PMPS by medical personnel. In this study, we conducted the survey by using questionnaire to assess current treatment and the recognitions of the medical personnel. METHODS: We mailed a questionnaire to 647 specialist members of the Breast Cancer Society. RESULTS: Of those, 34.7 % responsed. While PMPS was recognized by as much as 70.5 % of responding physicians, it was treated by as little as 47.7 % of the responders. In addition, while non-steroidal anti-inflammatory drugs (NSAIDs), which were ineffective in relieving PMPS, were used by 78.4 % of the responders, effective drugs were rarely used; therefore, treatment was considered ineffective by 69.5 %. This indicates that appropriate therapies are not widely used, and none of the current therapies are very effective. CONCLUSIONS: The results showed high recognition of PMPS pathology among physicians, but the treatment rate was as low as 47.7 %. NSAIDs were the main treatment, and the treatment effects were not satisfactory. It was revealed that currently appropriate treatment modalities have not been widely used. Education of physicians, distribution of treatment information and further studies are considered necessary for the spread of appropriate treatment modality.


Subject(s)
Breast Neoplasms/surgery , Chronic Pain/etiology , Mastectomy/adverse effects , Pain, Postoperative/etiology , Physicians , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Asian People , Attitude of Health Personnel , Female , Health Surveys , Humans , Male , Pain, Postoperative/therapy , Patient Education as Topic , Surveys and Questionnaires
11.
Masui ; 62(7): 822-8, 2013 Jul.
Article in Japanese | MEDLINE | ID: mdl-23905405

ABSTRACT

The treatment of chronic pain, whether of cancer or noncancer origin, frequently involves the use of opioids. Delay in GI transit and constipation are the most common and often disabling side effects of opioid analgesics. Many treatments involving laxatives and prokinetic drugs have been explored to circumvent opioid-induced bowel dysfunction, but the outcome has in general been unsatisfactory. Specific antagonism of peripheral opioid receptors offers a more rational approach to the management of the adverse actions of opioid analgesics in the gut. This goal is currently addressed by the use of opioid receptor antagonists with limited absorption such as oral naloxone and by the development of peripheral opioid receptor antagonists such as methylnaltrexone and alvimopan. These drugs hold considerable promise in preventing constipation due to treatments with opioids, whereas the analgesic action of opioids remains unabated.


Subject(s)
Analgesics, Opioid/adverse effects , Chronic Pain/drug therapy , Constipation/chemically induced , Narcotic Antagonists , Constipation/drug therapy , Constipation/prevention & control , Humans
13.
Chem Biol Drug Des ; 80(5): 771-4, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22834682

ABSTRACT

H-Dmt-D-Arg-Phe-Lys-NH(2) ([Dmt(1)]DALDA) is a synthetic tetrapeptide with extraordinary selectivity for the mu-opioid receptor and is an extremely potent analgesic. [Dmt(1) ]DALDA is unusual in the way that the greater part of its analgesic potency appears to be produced by its actions in the spinal cord. Furthermore, [Dmt(1) ]DALDA inhibits norepinephrine re-uptake and is a mitochondria-targeted antioxidant. Such characteristics may make [Dmt(1)]DALDA particularly effective against neuropathic pain. The present study was designed to compare the effects of [Dmt(1)]DALDA and morphine on thermal hyperalgesia in an experimental neuropathic pain model. Neuropathic pain was induced in rats by surgical ligation of the L5 spinal nerve, and thermal pain thresholds were assessed by latencies of paw withdrawal to radiant heat. The increase in paw withdrawal latency was greater after the administration of [Dmt(1) ]DALDA than that of morphine in neuropathic rats at doses that were equianalgesic in naïve animals. We conclude that [Dmt(1)]DALDA is more effective than morphine against thermal hyperalgesia in this experimental model of neuropathic pain.


Subject(s)
Analgesics, Opioid/therapeutic use , Morphine/therapeutic use , Neuralgia/drug therapy , Oligopeptides/therapeutic use , Animals , Male , Rats , Rats, Sprague-Dawley , Receptors, Opioid, mu/agonists
14.
Pharmacology ; 89(3-4): 145-8, 2012.
Article in English | MEDLINE | ID: mdl-22414674

ABSTRACT

BACKGROUND/AIMS: Multiple opioid receptor (OR) types and endogenous opioid peptides exist in the spinal dorsal horn and there may be interactions among these receptor types that involve opioid peptides. In a previous study we observed that antinociceptive effects of the selective κ-opioid receptor (κOR) agonist, U50,488H, was attenuated in µ-opioid receptor (µOR) knockout mice as compared to wild-type mice when administered spinally. This suggests that an interaction between κORs and µORs exits in the spinal cord. The present study was aimed at investigating whether endogenous opioid peptides were involved in such interaction. METHODS: We examined whether the presence of antibodies to endogenous opioid peptides, endomorphin-2, met-enkephalin and dynorphin A affected the antinociceptive effects of spinal U50,488H in rats. The tail-flick test was used to assess pain thresholds. RESULTS: The increase in tail-flick latency after spinal U50,488H was attenuated when the rats were pretreated intrathecally with antiserum against endomorphin-2. Pretreatments with antisera against met-enkephalin and dynorphin A had no effect on U50,488H antinociception. The antisera alone did not affect pain threshold. CONCLUSION: The results suggest that endomorphin-2, an endogenous opioid peptide highly selective to the µOR, plays a role in antinociception induced by κOR activation in the spinal cord.


Subject(s)
Oligopeptides/physiology , Pain/physiopathology , Receptors, Opioid, kappa/physiology , Spinal Cord/physiology , 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer/therapeutic use , Analgesics, Non-Narcotic/therapeutic use , Animals , Dynorphins/physiology , Enkephalin, Methionine/physiology , Male , Pain/drug therapy , Rats , Rats, Sprague-Dawley , Receptors, Opioid, mu/physiology
15.
Masui ; 60(9): 1032-6, 2011 Sep.
Article in Japanese | MEDLINE | ID: mdl-21950034

ABSTRACT

This chapter focuses on what social pain is and how it should be managed. In order to understand social pain in a cancer patient, it is necessary to recognize the change in the patient's daily life after the diagnosis of cancer. Because the degree of suffering and the relationships with family members and the people he or she worked with differ from patient to patient, it is important to note that the context of social pain is different in each patient. Five points shown below are essential in managing social pain. 1. Economical suffering may be alleviated by utilization of the social security system while taking into account each patient's standard of living. 2. Burdens on family members should be lessened, such as by not having them stay at the patient's bedside every day and letting them go home occasionally. 3. The normal patterns of communication, support, and conflict in the family should be identified, and the extent to which they have been disrupted by the illness should be assessed. 4. It is important to understand the ethnic, cultural, and religious background of the patient and the potential impact of their influence on the individual and the illness. 5. Practical or emotional unfinished business that the patient has needs to be identified, and efforts should be made to support fulfillment.


Subject(s)
Neoplasms/psychology , Humans , Interpersonal Relations , Neoplasms/economics , Role
16.
Masui ; 60(1): 96-9, 2011 Jan.
Article in Japanese | MEDLINE | ID: mdl-21348258

ABSTRACT

Here we report an anesthetic management of a 74-year-old man with gastric cancer and severe chronic obstructive pulmonary disease (COPD) undergoing endoscopic submucosal dissection (ESD). We maintained spontaneous breathing during ESD under monitored anesthesia care with dexmedetomidine (DEX). ESD lasted 5.5 hours with sufficient analgesia, and he required no airway management with the exception of supplemental mask oxygen during the procedures. He tolerated the procedure well and recovered with no complications. He was discharged without sequelae on the fifth postoperative day. DEX is a selective alpha2 agonist that has both sedative and analgesic properties, and it does not suppress ventilation. It should be used judiciously, and understanding the potential adverse effects and how to treat them is of paramount importance. However, with vigilant monitoring of blood pressure, heart rate, and level of consciousness during the ESD, it can be administered safely, thus lessening the anesthetic requirements and possibly improving the surgical outcome of the high risk patients. Especially, patients with severe COPD have demonstrated an increased risk for oxygen desaturation following general anesthesia, and to avoid this complication, spontaneous breathing sedation with DEX during ESD is one of the suitable management methods for COPD patients.


Subject(s)
Anesthesia, General , Dexmedetomidine , Gastric Mucosa/surgery , Gastroscopy , Hypnotics and Sedatives , Pulmonary Disease, Chronic Obstructive/complications , Stomach Neoplasms/surgery , Adrenergic alpha-2 Receptor Agonists , Aged , Analgesics , Humans , Male , Monitoring, Intraoperative , Severity of Illness Index , Stomach Neoplasms/complications
17.
Int J Clin Oncol ; 15(1): 46-51, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20072794

ABSTRACT

BACKGROUND: Neuropathic pain is regarded as one of the main causes of cancer pain refractory to standard opioid therapy in palliative care. The use of adjuvant analgesics for neuropathic cancer pain is largely empirical and the true efficacy of these adjuvant analgesics has been unknown. Gabapentin is one of the new promising anticonvulsant drugs as an adjuvant analgesic for neuropathic cancer pain. METHODS: The clinical usefulness of gabapentin in combination with opioids for Japanese patients with neuropathic cancer pain was assessed in an open-label, single-center, prospective study. Gabapentin was initiated in addition to the drugs currently being administered. The dose of gabapentin was titrated from 200 mg to a maximum dose of 2400 mg per day over 15 days, based on discussion with each patient. The primary endpoint variable was the numerical rating scale (NRS) of 0-10 measured using the brief pain inventory. RESULTS: From February 2007 to December 2007, gabapentin was administered to 24 patients that were already receiving an opioid without sufficient analgesia. Administration of gabapentin statistically reduced the worst-NRS, the least-NRS, and the average-NRS (7.3 --> 5.8, 3.6 --> 3.0, 5.8 --> 4.5, respectively). Four patients (16.7%) were withdrawn from the study because of adverse events (headache, myoclonus, heartburn, bronchial asthma). CONCLUSION: Although gabapentin might be regarded as a promising new adjuvant analgesic for neuropathic cancer pain, our results indicated that the decrease in pain score was of minimal clinical benefit. Controlled trials with other adjuvant analgesics are needed.


Subject(s)
Amines/administration & dosage , Analgesics, Opioid/administration & dosage , Analgesics/administration & dosage , Cyclohexanecarboxylic Acids/administration & dosage , Neoplasms/complications , Pain/drug therapy , gamma-Aminobutyric Acid/administration & dosage , Adult , Aged , Amines/adverse effects , Cyclohexanecarboxylic Acids/adverse effects , Female , Gabapentin , Humans , Japan , Male , Middle Aged , Pain/etiology , Pain Measurement , Palliative Care , Prospective Studies , gamma-Aminobutyric Acid/adverse effects
18.
Masui ; 59(12): 1498-501, 2010 Dec.
Article in Japanese | MEDLINE | ID: mdl-21229690

ABSTRACT

Negative pressure pulmonary edema (NPPE) has been described after acute airway obstruction. In the following case, we observed a rare occurrence of pulmonary edema caused by chronic tonsillar hypertrophy in a woman following removal of laryngeal mask airway (LMA). A 38-year-old woman with breast cancer underwent mastectomy under general anesthesia using the LMA. With the patient fully awake, the LMA was removed. Abruptly 7 minutes afterward, she showed signs of intense dyspnea, generalized rhonchus and progressive desaturation, and obstructive tonsillar hypertrophy was noticed. Acute lung edema was suspected and treatment started with oxygen therapy, bronchodilators, intravenous corticoids and loop diuretics. She was then intubated to secure airway and provide adequate ventilation with PEEP. Fortunately, the symptoms progressively remitted satisfactorily, and she was subsequently extubated 18 hours later with no complications. NPPE is an infrequent medical emergency and its early diagnosis and recognition are likely to lead to successful management of this potentially serious complication.


Subject(s)
Anesthesia, General , Laryngeal Masks/adverse effects , Palatine Tonsil/pathology , Postoperative Complications/etiology , Pulmonary Edema/etiology , Acute Disease , Adult , Breast Neoplasms/surgery , Bronchodilator Agents/therapeutic use , Early Diagnosis , Female , Humans , Hydrocortisone/administration & dosage , Hyperbaric Oxygenation , Hyperplasia , Positive-Pressure Respiration , Postoperative Complications/diagnosis , Postoperative Complications/therapy , Pulmonary Edema/diagnosis , Pulmonary Edema/therapy , Treatment Outcome
19.
Masui ; 59(12): 1534-8, 2010 Dec.
Article in Japanese | MEDLINE | ID: mdl-21229699

ABSTRACT

BACKGROUND: The Airway Scope (AWS) is a video laryngoscope and there are some problems associated with its use in insertion of the tracheal tube despite its ability to view the glottis. For the purpose of improving the problems, we devised the tube introducer catheter (TIC) for use with AWS. METHODS: Using the normal and fixed bent orotracheal tubes, wire-reinforced endotracheal tube, PORTEX and Phycon double lumen tubes, and Univent tube, TIC was attached to one of these tubes with AWS. And, we compared the efficacy and safety of the TIC with the AWS in facilitating tracheal intubation in a manikin model. RESULTS: With about all tubes, correct placement of the endotracheal tube was achieved in the TIC-facilitated tracheal intubations. In addition, the TIC can administer oxygen to prevent desaturation during the intubation. Excessive secretions in the oropharynx were effectively removed under vision with the TIC connected to the suction catheter. The topical anesthetics were sprayed on the vocal cords through the spray channels of the TIC. Furthermore, it can be used for exchange of tracheal tube in a patient. CONCLUSIONS: The TIC was significantly effective in facilitating tracheal intubation using the AWS in a manikin model.


Subject(s)
Catheters , Intubation, Intratracheal/instrumentation , Laryngoscopes , Manikins , Video Recording
20.
Masui ; 59(12): 1548-51, 2010 Dec.
Article in Japanese | MEDLINE | ID: mdl-21229702

ABSTRACT

BACKGROUND: One-lung ventilation and lung isolation are frequently required in thoracic surgery. In clinical practice, lung isolation is achieved by use of a double-lumen endotracheal tube and a bronchial blocker. A novel bagel shaped bronchial blocker, the Fuggiano's bronchial blocker, has been designed to prevent displacement of the blocker from its position in the bronchus. In this study, we evaluated the clinical performance of the Fuggiano's bronchial blocker for the lung isolation. METHODS: In thirty patients undergoing thoracotomy or video-assisted thoracoscopic surgery, the Fuggiano's bronchial blockers were placed to the bronchus. Fifteen patients received a left-sided bronchial block, and fifteen a right-sided block. The position of the devices was checked using fibreoptic bronchoscope. RESULTS: In all cases, successful lung isolation and the properly collapsed lung were achieved. It took significantly longer time to place a right bronchial block. Intraoperative repositioning of the device was not required. The quality of lung deflation was judged excellent in all patients. CONCLUSIONS: We conclude that, for routine use, the Fuggiano's bronchial blocker is preferable to achieve a lung isolation because of its facility in placement and a better quality of lung deflation. Fuggiano's bronchial blocker may be an alternative airway device for one-lung ventilation, and further work is required.


Subject(s)
Respiration, Artificial/instrumentation , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Intubation, Intratracheal/instrumentation , Male , Middle Aged , Thoracic Surgery, Video-Assisted , Thoracotomy , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL
...