Effects of lactation on pregnancy induced analgesia during the postpartum period in rats

Activation of an endogenous opioid system has been associated with an elevation in pain threshold during late pregnancy and the early postpartum period in rats. It is well established that endogenous opiates are involved in the physiological regulation on prolactin secretion. This study examined the influence of lactation on pregnancy-induced analgesia during the early postpartum period in rats. Three tests (colorectal distension, tail-flick and hot-plate) were used to assess each animal's response to painful stimuli. After determining pregnant baseline values, one group of rats (lactating, n = 21) were mated and retested on Day 7 and 21 of gestation and 1, 3, 5, 7 and 14 days after parturition. A non-lactating group of animals (n = 14) whose pups were removed immediately after delivery was tested in the same manner. On Day 21 of gestation significantly higher thresholds and longer latencies were observed. On Day 1 and 3 in both lactating and non-lactating rats, the values were still elevated. No significant difference was observed during the early postpartum period between the two groups. This study confirms the existence, in rats, of pregnancy-induced analgesia late in pregnancy and the early postpartum period. The analgesia during the early postpartum period is not influenced by lactation.     

Antinociceptive Interaction of Intrathecal alpha sub 2 -adrenergic Agonists, Tizanidine and Clonidine, with Lidocaine in Rats

Background: The intrathecal alpha2 -adrenergic agonist, clonidine, has been shown to have considerable antinociceptive effect, although clonidine causes hypotension and bradycardia The combination of intrathecal clonidine and local anesthetics enhances analgesic effects, whereas the combination may cause marked hypotension and motor blockade, which may limit the clinical application of the combination. Tizanidine, another alpha2 -adrenergic agonist, has also provided antinociception without producing pronounced hemodynamic changes. This study was designed to evaluate the antinociceptive and hemodynamic interactions of tizanidine and clonidine with lidocaine.

Methods: Male Sprague Dawley rats were chronically implanted with lumbar intrathecal catheters. The tail-flick test was used to assess the thermal nociceptive threshold. The ability of intrathecal tizanidine, clonidine, lidocaine, or the combinations of alpha2 -adrenergic agonist and lidocaine to alter the tail-flick latency was examined. To characterize the antinociceptive interaction, the isobolographic analysis was applied. Additionally, the motor function, blood pressure and heart rate after intrathecal administration of drugs and combinations were also monitored.

Results: Intrathecal tizanidine, clonidine, or the combinations increased the tail-flick latency in dose- and time-dependent fashion without affecting motor function. The order potencies (dose producing a 50% of peak effect, in micro gram) of tizanidine and clonidine were 1.8 and 0.75, respectively. With isobolographic analysis, tizanidine with lidocaine and clonidine with lidocaine showed significantly synergistic antinociceptive interaction. Potency ratio analysis and fractional analysis also confirmed the synergistic interaction. At the doses in the combinations showing comparable antinociception, tizanidine with lidocaine, unlike clonidine with lidocaine, did not affect motor function or blood pressure.     

The superiority of UW solution for maintaining ATP concentrations during pulmonary preservation

We evaluated three solutions used for preserving lungs, namely, University of Wisconsin (UW), Euro-Collins (E-C), and low potassium dextran (LPD), by measuring the high energy phosphates in the preserved lung tissue. The left lungs of Sprague-Dawley rats were excised and flushed with 5 ml of one of the solutions at 10°C through the pulmonary artery, after which they were deflated and immersed in the solution at 10°C for 24 h. The tissue adenosine triphosphate (ATP) concentration in mol/g tissue wet weight after 24 h of storage was 2.55 ± 0.48 (n = 7) in the UW lungs, 1.98 ± 0.25 (n = 6) in the E-C lungs, and 1.53 ± 0.32 (n = 4) in the LPD lungs, being significantly higher in the UW lungs than in either the E-C or LPD lungs (P < 0.05). The histopathological findings of the E-C lungs were more deteriorated, with marked interstitial edema, septal hypertrophy, and perivascular hyaline degeneration, than either the UW or LPD lungs. Thus, the findings of this study indicate the superiority of UW solution for lung preservation.     

In vitro effects of propofol on blood coagulability and fibrinolysis by the use of thromboelastograph technique

BACKGROUND: To investigate the in vitro effects of propofol on blood coagulability and fibrinolysis by the use of thromboelastograph (TEG) technique. METHODS: The blood samples, obtained from 14 healthy volunteers, were divided into two groups: propofol (n = 7) and intralipid (n = 7), and 360 microliters volumes of whole blood were incubated with 2 microliters of 1% propofol and with its solvent intralipid, respectively. The incubated sample was then used for TEG measurements. RESULTS: The maximum amplitude (MA), which reflects coagulability, in the intralipid group significantly increased by about 7% and 16% compared to the control and propofol groups, respectively (P < 0.05), whereas the MA in the propofol group did not change. The fibrinolytic rate (FR) in the propofol group significantly increased by about 170% and 210% compared to the control and intralipid groups, respectively (P < 0.05), whereas the FR in the intralipid group did not change. CONCLUSIONS: Propofol, per se, has at the concentration of 55.6 micrograms.ml-1 an in vitro accelerative effect on blood fibrinolysis detected by TEG.     

Epidural administration and analgesic spread: Comparison of injection with catheters and needles

This study was designed to investigate differences in epidural analgesic spread between catheter and needle injections in 48 patients with comparable physical characteristics. The spread of analgesia in the catheter injection group with a 0.24ml·sec^–1 injection rate (n = 16) was 16.8 ± 1.5 spinal segments and that in the needle injection group at the same injection rate (n = 16) was 12.5 ± 1.8 spinal segments (P 0.01). Needle injection at the faster rate of 1.2ml*237sec^–1 (n = 16) produced a significantly greater spread of analgesia than with the 0.24ml·sec^–1 rate through the needle (16.2 ± 1.6 vs 12.5 ± 1.8 spinal segments, P 0.01). Thirteen of 16 patients receiving the fast needle injection complained of back compression or discomfort during the injection.The injection through an epidural catheter and the fast (1.2ml·sec^–1) injection through a needle produced extensive and equivalent epidural analgesic spread. However, because of patients discomfort with fast injection through the needle, the authors conclude that when using continuous epidural anesthesia, the initial injection of local anesthetic should be administered through the epidural catheter not the needle.(Omote K, Namiki A, Iwasaki H: Epidural administration and analgesic spread: comparison of injection with catheters and needles. J Anesth 6: 289–293, 1992)     

Analgesic mechanisms of ketamine in the presence and absence of peripheral inflammation

BACKGROUND: The studies on the mechanisms of ketamine antinociception have led to conflicting results. In this study, the authors investigated the contribution of supraspinal monoaminergic descending inhibitory system to ketamine analgesia for acute nociception and inflammation-induced hyperalgesia. METHODS: Male Sprague-Dawley rats were used. The paw withdrawal latencies to radiant heat stimuli were measured to assess the thermal nociceptive threshold. The analgesic effects of intrathecal or intraperitoneal ketamine were examined in the rats that received unilateral intraplantar carrageenan and in those that were untreated. In addition, it was examined whether pretreatment with intrathecal yohimbine or methysergide inhibited the analgesic effects of ketamine. Using an intrathecal microdialysis method, noradrenaline and 5-hydroxytryptamine concentrations in lumbar cerebrospinal fluid were measured after intraperitoneal ketamine in both saline- and carrageenan-treated rats. RESULTS: In the untreated rats, intraperitoneal but not intrathecal ketamine produced antinociceptive effects in a dose-dependent manner. Pretreatment with intrathecal yohimbine or methysergide inhibited these antinociceptive effects. Intraplantar carrageenan significantly reduced paw withdrawal latencies on the injected paw but not on the contralateral paw. Both intraperitoneal and intrathecal ketamine reversed the shortened paw withdrawal latencies on the injected side in a dose-dependent manner without any effects on the contralateral side. Neither yohimbine nor methysergide inhibited these antihyperalgesic effects. In analyses of monoamines, the magnitude of increase in monoamines after intraperitoneal ketamine was significantly smaller in the carrageenan-treated rats than in the saline-treated rats. CONCLUSION: These results demonstrated that ketamine produced antinociceptive effects through an activation of the monoaminergic descending inhibitory system, whereas, in a unilateral peripheral inflammation-induced hyperalgesic state, the monoaminergic system did not contribute to the antihyperalgesic effects of ketamine. The mechanisms of the antinociceptive and antihyperalgesic properties of ketamine are different.     

Clinical evaluation of accuracy of a new disposable pump (Syrinjector) for continuous epidural infusion

We evaluated the accuracy of a new disposable pump (Coopdech Syrinjector), which employed the negative pressure made by injecting fluid into the pump for continuous epidural infusion. Thoracic epidural catheter was placed at the T6-T8 level prior to the lung surgery. The continuous epidural infusion of 0.25% bupivacaine at 2 or 3 ml.h-1 was started immediately after the surgery. The residual volume of bupivacaine was recorded. From our results, the injection speed of Syrinjector was satisfactory for clinical use of continuous epidural infusion of bupivacaine. However, when this pump is reused or the volume of the residual local anesthetics is less than 10 ml, the infusion accuracy will be potentially imprecise.     

Sofosbuvir plus ribavirin in Japanese patients with chronic genotype 2 HCV infection: an open‐label,phase 3 trial

Genotype 2 hepatitis C virus (HCV) accounts for up to 30% of chronic HCV infections in Japan. The standard of care for patients with genotype 2 HCV – peginterferon and ribavirin for 24 weeks – is poorly tolerated, especially among older patients and those with advanced liver disease. We conducted a phase 3, open‐label study to assess the efficacy and safety of an all‐oral combination of the NS5B polymerase inhibitor sofosbuvir and ribavirin in patients with chronic genotype 2 HCV infection in Japan. We enrolled 90 treatment‐naïve and 63 previously treated patients at 20 sites in Japan. All patients received sofosbuvir 400 mg plus ribavirin (weight‐based dosing) for 12 weeks. The primary endpoint was sustained virologic response at 12 weeks after therapy (SVR12). Of the 153 patients enrolled and treated, 60% had HCV genotype 2a, 11% had cirrhosis, and 22% were over the aged 65 or older. Overall, 148 patients (97%) achieved SVR12. Of the 90 treatment‐naïve patients, 88 (98%) achieved SVR12, and of the 63 previously treated patients, 60 (95%) achieved SVR12. The rate of SVR12 was 94% in patients with cirrhosis and in those aged 65 and older. No patients discontinued study treatment due to adverse events. The most common adverse events were nasopharyngitis, anaemia and headache. Twelve weeks of sofosbuvir and ribavirin resulted in high rates of SVR12 in treatment‐naïve and previously treated patients with chronic genotype 2 HCV infection. The treatment was safe and well tolerated by patients, including the elderly and those with cirrhosis.