Presepsin and prognostic nutritional index are predictors of septic acute kidney injury, renal replacement therapy initiation in sepsis patients, and prognosis in septic acute kidney injury patients: a pilot study.

BACKGROUND: Sepsis is the most common cause of acute kidney injury (AKI) among critically ill patients. This study aimed to determine whether presepsin is a predictor of septic acute kidney injury, renal replacement therapy initiation (RRTi) in sepsis patients, and prognosis in septic AKI patients. METHODS: Presepsin values were measured immediately after ICU admission (baseline) and on Days 2, 3, and 5 after ICU admission. Glasgow Prognostic Score (GPS), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio, Prognostic Index, and Prognostic Nutritional Index (PNI) were measured at baseline, and total scores ("inflammation-presepsin scores [iPS]") were calculated for category classification. Presepsin values, inflammation-based prognostic scores, and iPS were compared between patients with and without septic AKI or RRTi and between survivors and non-survivors. RESULTS: Receiver operating characteristic curve analyses identified the following variables as predictors of septic AKI and RRTi in sepsis patients: presepsin on Day 1 (AUC: 0.73) and Day 2 (AUC: 0.71) for septic AKI, and presepsin on Day 1 (AUC: 0.71), Day 2 (AUC: 0.9), and Day 5 (AUC: 0.96), Δpresepsin (Day 2 - Day 1) (AUC: 0.84), Δpresepsin (Day 5 - Day 1) (AUC: 0.93), and PNI (AUC: 0.72) for RRTi. Multivariate logistic regression analyses identified presepsin on Day 2 as a predictor of prognosis in septic AKI patients. CONCLUSIONS: Presepsin and PNI were found to be predictors of septic AKI, RRTi in sepsis patients, and prognosis in septic AKI patients.

Efficacy of Goreisan in Preventing Transurethral Resection Syndrome in Transurethral Resection of the Prostate: A Randomized-Controlled Study.

Objectives: Nonconductive irrigation fluids used during transurethral resection (TUR) of the prostate can cause fluid overload and dilutional hyponatremia. TUR syndrome is generally defined as serum sodium at or below 125 mmol/L with cardiovascular and neurologic symptoms. The aim of this study was to evaluate the effects of Goreisan, a traditional Japanese Kampo medicine, on serum sodium levels and the occurrence of TUR syndrome in patients undergoing TUR of the prostate. Design: This was a randomized-controlled trial. Settings/Location: This trial was conducted at the Osaka Medical College Hospital and Keneikai Sanko Hospital. Subjects: Fifty patients scheduled for TUR of the prostate were included. Interventions: Patients in the Goreisan group (n = 23) received 2.5 g Goreisan orally on the night before surgery and on the morning of surgery. The control group (n = 27) did not receive Goreisan. Surgical procedures, perioperative management, and patient monitoring were otherwise the same in both groups. Outcome Measures: The primary outcome was occurrence of TUR syndrome. The secondary outcome was serum sodium level. Results: Serum sodium remained above 125 mmol/L in all patients, so none of the patients met the criteria for TUR syndrome. However, the Goreisan group had significantly higher intraoperative sodium levels (p < 0.001) and significantly higher intraoperative (p = 0.008) and postoperative (p = 0.02) hemoglobin levels than the control group. Conclusions: These findings indicate that preoperative Goreisan administration can help maintain serum sodium levels in patients undergoing TUR of the prostate.

Yokukansan Alleviates Cancer Pain by Suppressing Matrix Metalloproteinase-9 in a Mouse Bone Metastasis Model.

Bone cancer pain control is difficult because it includes various characteristics of pain such as nociceptic and neuropathic pain. In this study, we investigated the effect of yokukansan (YKS), one of the traditional Japanese herbal medicines, on cancer pain in mouse bone metastasis model. Oral administration of YKS significantly alleviated pain behavior measured by quantitative body weight bearing. Furthermore, the pain behavior was also significantly alleviated by intrathecal and intraperitoneal administration of matrix metalloproteinase- (MMP-) 9 inhibitor, but not of MMP-2 inhibitor. MMP-9 expression was significantly elevated in the bone tissue on day 3 after carcinoma cell injection and in the ipsilateral spinal cord on day 7, which was suppressed by YKS administration. Taken together, these results suggest that YKS alleviates cancer pain via suppressing MMP-9 expression in bone metastasis model in mice.

Corrigendum to "Yokukansan Alleviates Cancer Pain by Suppressing Matrix Metalloproteinase-9 in a Mouse Bone Metastasis Model".

[This corrects the article DOI: 10.1155/2019/2956920.].

Preoperative Administration of Jidabokuippo, a Kampo Medicine, Alleviates Postoperative Pain after Tooth Extraction with Mandible Bone Removal under General Anesthesia: A Prospective, Single-Blind, Randomized Controlled Trial.

OBJECTIVE: This study aimed to determine the efficacy of preoperative administration of Jidabokuippo (JDI), a Kampo medicine, in treating postoperative pain after tooth extraction with mandible bone removal. DESIGN: This single-blind, randomized controlled study was conducted among two groups of adult patients who were scheduled to undergo tooth extraction with mandible bone removal under general anesthesia. Patients were randomly assigned to either the JDI or control group. INTERVENTION: Before surgery, the JDI group received JDI (7.5 g), whereas the control group did not receive any treatment. Patients and the evaluator were blinded to the treatment status. At 0, 1, 3, and 24 h after anesthesia recovery, an investigator recorded the severity of postoperative pain and nausea using a numeric rating scale (0, no pain or nausea; 10, worst imaginable pain or nausea). The number of patients who requested nonsteroidal anti-inflammatory drug (NSAID) and that of additional NSAID administration within 24 h from anesthesia recovery, and the time to the first NSAID request from anesthesia recovery was also measured. RESULTS: The severity of postoperative pain was significantly lower in the JDI group compared with the control group at 3 and 24 h after anesthesia recovery (p < 0.001 each). Both the number of patients requesting NSAID and additional NSAID administration after anesthesia recovery were significantly smaller in the JDI group than in the control group (p = 0.006, p < 0.001). The time to first NSAID request from anesthesia recovery was significantly longer in the JDI group compared with control group (p < 0.001). The severity of nausea did not differ significantly between the groups. No significant side effects related to JDI were noted during the trial. CONCLUSIONS: JDI administration before general anesthesia effectively decreased the severity of postoperative pain after anesthesia recovery in patients who underwent tooth extraction with mandible bone removal.

[Efficacy of Go-rei-san for Pain Management in Four Patients with Intractable Trigeminal Neuralgia].

Go-rei-san is a Japanese traditional medicine that is used to treat motion sickness, nausea, and vomiting. We report here four patients for whom Go-rei-san was effective in treating pain associated with intractable trigeminal neuralgia. Three patients could not continue carbamazepine due to drug-induced rash, liver damage, and gastrointestinal injury, and suffered from pain. One patient experienced severe dizziness upon combination treatment with pregabalin and carbamazepine. All patients exhibited symptoms of water poisoning on their tongues. All patients experienced significant pain relief without major complications after daily adminis- tration of 7.5 g Go-rei-san. Our findings suggest that Go-rei-san can effectively alleviate pain associated with intractable trigeminal neuralgia without major compli- cations.

Preoperative Oral Administration of Kikyo-To, a Kampo Medicine, Alleviates Postoperative Sore Throat: A Prospective, Double-Blind, Randomized Study.

OBJECTIVES: This study aimed to determine the efficacy of Kikyo-To (KKT), a Kampo medicine, in treating postoperative sore throat and nausea. DESIGN: This randomized, controlled, double-blind study was conducted among two groups of women who were scheduled to undergo benign surgery under general anesthesia. All patients had a physical status of 1 (normal, healthy patient) or 2 (patient with a mild systemic disease), according to the American Society of Anesthesiologists criteria. Patients were randomly assigned to the KKT group or the placebo (control) group. INTERVENTION: Before surgery, the KKT group received KKT (5.0 g) mixed with jelly, while the placebo group received only jelly. Patients and the evaluator were blinded to the treatment status. OUTCOME MEASURES: At 0, 3, and 24 hours after anesthesia recovery, an investigator (also blinded to the treatment status) recorded the incidence and severity (using the Numeric Rating Scale [NRS]) of sore throat and nausea. RESULTS: The incidence of sore throat was significantly lower in the KKT group than in the control group immediately after surgery (p < 0.05). The severity of sore throat on the NRS was significantly lower in the KKT group than in the control group immediately and 3 hours after surgery (p < 0.05). In contrast, the incidence and severity of nausea did not differ significantly between the two groups. CONCLUSIONS: KKT administration before general anesthesia did not alleviate postoperative nausea but effectively decreased the incidence and severity of postoperative sore throat in women undergoing benign surgery.

Preventive Effect of Preoperative Administration of Hange-Shashin-To on Postoperative Sore Throat: A Prospective, Double-Blind, Randomized Trial.

OBJECTIVES: The present study aimed to determine the efficacy of Hange-Shashin-To (HST), a Kampo medicine, in treating postoperative sore throat and nausea. DESIGN: This randomized, controlled, double-blind study was conducted among two groups of adult female patients who were scheduled to undergo benign laparoscopic surgery under general anesthesia. All patients in each group had a physical status of either 1 (normal, healthy patient) or 2 (patient with a mild systemic disease), according to the American Society of Anesthesiologists. Patients were randomly assigned to either the HST group or the placebo (control) group. INTERVENTION: Before surgery, the HST group received HST (5.0 g) mixed with jelly, while the placebo group received only jelly. Patients and the evaluator were blinded to the treatment status. OUTCOME MEASURES: At 0, 3, and 24 hours after anesthesia recovery, an investigator (also blinded to the treatment status) recorded incidence and severity using the Numeric Rating Scale for sore throat and nausea. RESULTS: Incidence and severity of sore throat were significantly lower in the HST group than in the control group immediately and 3 hours after surgery (p<0.05). In contrast, incidence and severity of nausea did not differ significantly between the HST and control groups. CONCLUSIONS: HST administration before general anesthesia did not alleviate postoperative nausea, but effectively decreased the incidence and severity of postoperative sore throat in female patients undergoing laparoscopic surgery.

Change in serum sodium level predicts clinical manifestations of transurethral resection syndrome: a retrospective review.

BACKGROUND: Patients undergoing transurethral resection (TUR) of the prostate are at risk of TUR syndrome, generally defined as having cardiovascular and/or neurological manifestations, along with serum sodium concentrations less than or equal to 125 mmol/l. As these symptoms can also occur in patients with serum sodium greater than 125 mmol/l, this study aimed to investigate the relationship between serum sodium concentrations and neurological manifestations of TUR syndrome. METHODS: Data on patients who underwent TUR of the prostate under local anesthesia over an 8-year period were retrospectively reviewed. Based on their cardiovascular and neurological manifestations, patients were divided into two groups: a symptomatic and an asymptomatic group. Logistic regression analysis was used to detect the risk factors for being symptomatic. Receiver operator characteristic (ROC) curve analysis was used to determine the optimal cutoff value of estimated change in serum sodium level that could predict the development of clinical manifestation of TUR syndrome. RESULTS: Of the 229 patients, 60 showed symptoms. Serum sodium level correlated with neurological score (Spearman's correlation coefficient > 0.5). Logistic regression detected that the risk factors for being symptomatic were serum sodium level variables, operation time longer than or equal 90 min, and presence of continuous drainage from the bladder. ROC curve analysis showed that a change in serum sodium level of 7.4 mmol/l was the optimal cutoff value, with a sensitivity of 0.72, a specificity of 0.87, and an area under the curve (AUC) of 0.87. ROC curve analysis also showed that a 7.0% change in serum sodium level was optimal for this parameter, with a sensitivity of 0.70, a specificity of 0.89, and an AUC of 0.87. CONCLUSIONS: Changes in serum sodium concentration of > 7 mmol/l and of > 7% could predict the development of cardiovascular and neurological manifestations, which were assumed to be symptoms of TUR syndrome.

Intermittent but not sustained hypoxia activates orexin-containing neurons in mice.

Hypothalamic orexin-containing neurons are activated by CO2 and contribute to hypercapnic ventilatory activation. However, their role in oxygen-related regulation of breathing is not well defined. In this study, we examined whether an experimental model mimicking apnea-induced repetitive hypoxemia (intermittent hypoxia [IH]) activates orexin-containing neurons. Mice were exposed to IH (5×5min at 10% O2), intermittent hyperoxia (IO; 5×5min at 50% O2), sustained hypoxia (SH; 25min at 10% O2), or sham stimulation. Their brains were examined using double immunohistochemical staining for orexin and c-Fos. The results indicated that IH (25.8±3.0%), but not SH (9.0±1.5%) activated orexin-containing neurons when compared to IO (5.5±0.6%) and sham stimulation (5.9±1.4%). These results correlate with those of our previous work showing that IH-induced respiratory long-term facilitation is dependent on orexin-containing neurons. Taken together, orexin contributes to repetitive hypoxia-induced respiratory activation and the hypoxic activation of orexin-containing neurons is pattern dependent.

[Successful use of "juzen-taiho-to", a kampo medicine, for the treatment of perioperative anemia and hypoalbuminemia].

An 88-year-old woman suffering from femoral neck fracture was transported to the emergency room of a hospital. The patient and her family refused transfusion, despite anemia, stating their affiliation with Jehova's Witnesses. Surgery was performed under general anesthesia, and the following day, anemia (hemoglobin, 7.5 g x dl(-1)) and hypoalbuminemia (albumin, 2.7 g x dl(-1)) were observed, in addition to anorexia and general fatigue. The patient underwent nutritional treatment with a kampo medicine (Juzen-taiho-to), which was administered as a medication due to difficulties with swallowing the powdered form. On the 18th day after admission, anemia (hemoglobin, 8.9 g x dl(-1)) and hypoalbuminemia (3.6 g x dl(-1)) improved, as did anorexia and general fatigue. It is thought that the components Shimotsu-to, a component known to improve anemia, and Shikunshi-to, a vital energy supplementing component, were the main ingredients that conferred the improvements in anemia and hypoalbuminemia. These findings suggest that Chinese herbal medicine for the nutritional treatment of the elderly has minimal side effects.

Prediction of clinical manifestations of transurethral resection syndrome by preoperative ultrasonographic estimation of prostate weight.

BACKGROUND: This study aimed to investigate the relationship between preoperative estimated prostate weight on ultrasonography and clinical manifestations of transurethral resection (TUR) syndrome. METHODS: The records of patients who underwent TUR of the prostate under regional anesthesia over a 6-year period were retrospectively reviewed. TUR syndrome is usually defined as a serum sodium level of < 125 mmol/l combined with clinical cardiovascular or neurological manifestations. This study focused on the clinical manifestations only, and recorded specific central nervous system and cardiovascular abnormalities according to the checklist proposed by Hahn. Patients with and without clinical manifestations of TUR syndrome were compared to determine the factors associated with TUR syndrome. Receiver operating characteristic curve analysis was used to determine the optimal cutoff value of estimated prostate weight for the prediction of clinical manifestations of TUR syndrome. RESULTS: This study included 167 patients, of which 42 developed clinical manifestations of TUR syndrome. There were significant differences in preoperative estimated prostate weight, operation time, resected prostate weight, intravenous fluid infusion volume, blood transfusion volume, and drainage of the suprapubic irrigation fluid between patients with and without clinical manifestations of TUR syndrome. The preoperative estimated prostate weight was correlated with the resected prostate weight (Spearman's correlation coefficient, 0.749). Receiver operator characteristic curve analysis showed that the optimal cutoff value of estimated prostate weight for the prediction of clinical manifestations of TUR syndrome was 75 g (sensitivity, 0.70; specificity, 0.69; area under the curve, 0.73). CONCLUSIONS: Preoperative estimation of prostate weight by ultrasonography can predict the development of clinical manifestations of TUR syndrome. Particular care should be taken when the estimated prostate weight is > 75 g.

Transurethral resection syndrome in elderly patients: a retrospective observational study.

BACKGROUND: Transurethral resection of the prostate (TURP) involves the risk of transurethral resection (TUR) syndrome owing to hyponatremia. Irrigation fluid type, duration of operation, and weight of resected mass have been evaluated as risk factors for TUR syndrome. The purpose of the present study was to identify risk factors related to TUR syndrome in the elderly. METHODS: After obtaining approval from the Institutional Review Board, data on all elderly males (aged 70 years and older) who underwent TURP under regional anesthesia over a 6-year period at our institution were retrospectively reviewed. TUR syndrome was defined as evidence of a central nervous system disturbance such as nausea, vomiting, restlessness, confusion, or even coma with a circulatory abnormality both intra- and post-operatively. Patients were divided into two groups, positive and negative, for the occurrence of the syndrome. Data such as previous medical history, preoperative and postoperative serum data, weight of resected mass, duration of operation, irrigation fluid drainage technique, anesthetic technique, operative infusion and transfusion volume, and neurological symptoms were collected. Only observational variables with p < 0.05 on univariate analyses were included in the multivariate logistic regression model to ascertain their independent effects on TUR syndrome. RESULTS: Of the 98 patients studied, 23 had TUR syndrome (23.5%, 95% confidence interval [CI] 14.9-32.0%). Multivariate regression analysis revealed that volume of plasma substitute ≥ 500 ml (odds ratio [OR] 14.7, 95% CI 2.9-74.5), continuous irrigation through a suprapubic cystostomy (OR 4.7, 95% CI 1.3-16.7), and weight of resected mass > 45 g (OR 4.1, 95% CI 1.2-14.7) were associated with significantly increased risks for TUR syndrome (Hosmer-Lemeshow test, p = 0.94, accuracy 84.7%). CONCLUSIONS: These results suggest that the use of a plasma substitute and continuous irrigation through a suprapubic cystostomy must be avoided during TURP procedures in the elderly.

Go-rei-San, a Kampo medicine, reduces postoperative nausea and vomiting: a prospective, single-blind, randomized trial.

OBJECTIVE: The objective of this study was to determine the efficacy of Go-rei-San (GRS), a Kampo medicine, in the treatment of postoperative nausea, vomiting, or both nausea and vomiting (PONV). DESIGN: The study was a randomized, controlled, single-blind study of two groups of adult female patients who were scheduled to undergo benign gynecological laparoscopic surgery under general anesthesia. Patients in each group possessed an American Society of Anesthesiologists physical status of 1 (normal, healthy patient) to 2 (patient with a mild systemic disease). Patients were randomly assigned to the GRS group or the no-intervention group. INTERVENTION: Patients in the GRS group were given 7.5 g of GRS orally the day before surgery. OUTCOME MEASURES: The primary outcome measure was the severity of nausea at 0-3 h and 0-24 h after tracheal extubation. The secondary outcome measures were the incidence of vomiting at 0-3 h and 0-24 h and the frequency of vomiting at 0-24 h. The severity of nausea was measured by the patient, who used an 11-point verbal scale to indicate her strongest nausea. RESULTS: Of the 100 female patients selected for the study, 99 completed the trial, and no adverse events occurred. The severity of nausea, frequency of vomiting, and incidence of vomiting were significantly lower in the GRS group than in the no-intervention group. CONCLUSIONS: This study suggests that GRS may be effective for the reduction of PONV.

A synthetic kainoid, (2S,3R,4R)-3-carboxymethyl-4-(phenylthio)pyrrolidine-2-carboxylic acid (PSPA-1) serves as a novel anti-allodynic agent for neuropathic pain.

In spite of prominent progress in basic pain research, neuropathic pain remains a significant medical problem, because it is often poorly relieved by conventional analgesics. Thus this situation encourages us to make more sophisticated efforts toward the discovery of new analgesics. We previously showed that i.t. administration of acromelic acid-A (ACRO-A), a Japanese mushroom poison, provoked prominent tactile pain (allodynia) at an extremely low dose of 1 fg/mouse. In the present study we synthesized ACRO-A analogues (2S,3R,4R)-3-carboxymethyl-4-phenoxypyrrolidine-2-carboxylic acid (POPA-2) and (2S,3R,4R)-3-carboxymethyl-4-(phenylthio)pyrrolidine-2-carboxylic acid (PSPA-1) chemically and examined their ability to induce allodynia in conscious mice. Whereas POPA-2 induced allodynia at extremely low doses from 1 to 100 fg/mouse, similar to ACRO-A, PSPA-1 did not induce allodynia; rather, it inhibited the ACRO-A-induced allodynia with an ID(50) value (95% confidence limits) of 2.19 fg/mouse (0.04-31.8 fg/mouse). Furthermore, PSPA-1 relieved neuropathic pain produced by L5 spinal nerve transection on day 7 after the operation in a dose-dependent manner from 1 to 100 pg/mouse. In contrast, it did not affect thermal or mechanical nociception or inflammatory pain. PSPA-1 reduced the increase in neuronal nitric oxide synthase activity in the spinal cord of neuropathic pain mice assessed by NADPH-diaphorase histochemistry and blocked the allodynia induced by N-methyl-d-aspartate. These results demonstrate that PSPA-1 may represent a novel class of anti-allodynic agents for neuropathic pain acting by blocking the glutamate-nitric oxide pathway.

[Epidural blood patch for intracranial hypotension with closed system in a Jehovah's Witness].

We report a case of treating intracranial hypotension with an epidural blood patch using closed system that allows blood collection and epidural injection without loss of continuity. The patient was a 34-year-old woman with severe headache for several months. The headache failed to respond to conservative management. By radioisotope cisternography, it was diagnosed as intracranial hypotension. Epidural blood patch was planned for intracranial hypotension. We used the method of epidural blood patch in a closed venous blood transfusion system to the epidural space, because she is a member of the Jehovah's Witness. Twenty five ml of blood was drawn into the syringe and injected into the epidural space with closed system. The patient was discharged home after 3 days with dramatically reduced symptons. Epidural blood patching with closed system is a safe, and effective procedure that is acceptable to a Jehovah's Witness.

Analgesic effect of extracts of Chinese medicinal herbs Moutan cortex and Coicis semen on neuropathic pain in mice.

Neuropathic pain arising from peripheral nerve injury is a clinical disorder characterized by a combination of spontaneous pain, hyperalgesia and tactile pain (allodynia), and remains a significant clinical problem since it is often poorly relieved by conventional analgesics. To seek an analgesic compound(s) in Chinese herbs, we examined the effect of seven Chinese herbs that are routinely prescribed for pain management in two neuropathic pain models: allodynia induced by intrathecal administration of prostaglandin F2alpha (PGF2alpha) and by selective L5 spinal nerve transection. The extracts of Moutan cortex and Coicis semen dose-dependently alleviated the PGF2alpha-induced allodynia by oral administration 1 h before intrathecal injection of PGF2alpha. When orally administrated every day for 7 days, these extracts attenuated neuropathic pain in the ipsilateral side, but not in the contralateral side, day 7 after L5 spinal nerve transection. The increase in NADPH diaphorase activity in the spinal cord associated with neuropathic pain was also blocked by these extracts. These results suggest that Moutan cortex and Coicis semen contain substances effective in neuropathic pain.

Acute and late effects on induction of allodynia by acromelic acid, a mushroom poison related structurally to kainic acid.

1. Ingestion of a poisonous mushroom Clitocybe acromelalga is known to cause severe tactile pain (allodynia) in the extremities for a month and acromelic acid (ACRO), a kainate analogue isolated from the mushroom, produces selective damage of interneurons of the rat lower spinal cord when injected either systemically or intrathecally. Since ACRO has two isomers, ACRO-A and ACRO-B, here we examined their acute and late effects on induction of allodynia. 2. Intrathecal administration of ACRO-A and ACRO-B provoked marked allodynia by the first stimulus 5 min after injection, which lasted over the 50-min experimental period. Dose-dependency of the acute effect of ACRO-A on induction of allodynia showed a bell-shaped pattern from 50 ag x kg(-1) to 0.5 pg x kg(-1) and the maximum effect was observed at 50 fg x kg(-1). On the other hand, ACRO-B induced allodynia in a dose-dependent manner from 50 pg x kg(-1) to 50 ng x kg(-1). 3. N-methyl-d-aspartate (NMDA) receptor antagonists and Joro spider toxin, a Ca(2+)-permeable AMPA receptor antagonist, inhibited the allodynia induced by ACRO-A, but not by ACRO-B. However, other AMPA/kainate antagonists did not affect the allodynia induced by ACRO. 4. Whereas no neuronal damage was observed in the spinal cord in ACRO-A-treated mice, induction of allodynia by ACRO-A (50 fg x kg(-1)) and ACRO-B (50 ng x kg(-1)) was selectively lost 1 week after i.t. injection of a sublethal dose of ACRO-A (50 ng x kg(-1)) or ACRO-B (250 ng x kg(-1)). Higher doses of ACRO-A, however, could evoke allodynia dose-dependently from 50 pg x kg(-1) to 500 ng x kg(-1) in the ACRO-A-treated mice. The allodynia induced by ACRO-A (500 ng x kg(-1)) was not inhibited by Joro spider toxin or NMDA receptor antagonists. These properties of the late allodynia induced by ACRO-A were quite similar to those of the acute allodynia induced by ACRO-B. 5. ACRO-A could increase [Ca(2+)](i) in the deeper laminae, rather than in the superficial laminae, of the spinal cord. This increase was not blocked by the AMPA-preferring antagonist GYKI52466 and Joro spider toxin. 6. Taken together, these results demonstrate the stereospecificity of ACRO for the induction of allodynia and suggest the presence of a receptor specific to ACRO.

Allodynia evoked by intrathecal administration of prostaglandin E2 to conscious mice.

We recently reported that intrathecal (i.t) administration of prostaglandin (PG) F2 alpha to conscious mice induced allodynia that was elicited by non-noxious brushing of the flanks. In the presents study, we demonstrate that i.t. administration of PGD2 and PGE2 to conscious mice also results in allodynia. Dose dependency of PGD2 for allodynia showed a skewed bell-shaped pattern (0.1 ng-2.5 micrograms/mouse), and the maximal allodynic effect was observed with 1.0 microgram at 15 min after intrathecal injection. PGD2-induced allodynia showed a time course and dose dependency similar to that induced by PGF2 alpha, but with lower scores. On the other hand, dose dependency of PGE2 for allodynia showed a bell-shaped pattern over a wide range of dosage from 10 fg to 2.0 micrograms/mouse. The maximal allodynic effect was observed with 0.01-0.1 microgram at 5 min after i.t. injection, and the response gradually decreased over the experimental period of 50 min. Intrathecally administered strychnine and the GABAA antagonist bicuculline also induced allodynia in conscious mice. The time courses of allodynia evoked by strychnine and bicuculline coincided with those by PGE2 and PGF2 alpha, respectively. PGE2-induced allodynia was dose-dependently relieved by the strychnine-sensitive glycine receptor agonist taurine, the NMDA receptor antagonist ketamine, and a high dose of the alpha 2-adrenergic agonist clonidine, but not by the GABAA agonist muscimol or by the GABAB agonist baclofen. In contrast, PGF2-induced allodynia was dramatically inhibited by clonidine and baclofen, but not by taurine, ketamine or muscimol.(ABSTRACT TRUNCATED AT 250 WORDS)