[Development and evaluation of a patient-reported outcome measure of pain-related sleep disturbances for pain clinic patients].

BACKGROUND: The purpose of this study was to develop a new tool, the Pain Sleep questionnaire, consisting of 20 items (PS-20) for measuring pain-related sleep disturbances in pain clinic patients, and to examine its reliability and validity. METHODS: The internal consistency, criterion validity compared with the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36v2), and construct validity of the PS-20 were tested. RESULTS: A total of 125 patients participated in this study. Cronbach's alpha coefficient was 0.969, indicating good internal consistency. The PS-20 score correlated moderately with the physical component summary of SF-36v2 and correlated weakly with the mental component summary of SF-36v2. From the graphical model using the Akaike information criterion and the Categorical principal component analysis, the items were divided into four domains: physical pain, trouble falling asleep, awakened by pain, and general health problems. CONCLUSIONS: The PS-20 was shown to be a valid and reliable questionnaire scale for measuring pain-related sleep disturbances among pain clinic patients.

Replacement of gabapentin with pregabalin in postherpetic neuralgia therapy.

PURPOSE: Although both gabapentin and pregabalin are first-line drugs for neuropathic pain including postherpetic neuralgia (PHN), no report has directly compared the magnitude of pain relief and the incidence of side effects of both drugs. By substituting gabapentin with pregabalin in postherpetic neuralgia therapy, we can compare the two drugs. METHODS: In 32 PHN patients being administered gabapentin, without changing the frequency of dosing, the drug was substituted with pregabalin at one-sixth dosage of gabapentin. After 2 weeks, an interview was conducted about the visual analog scale (VAS) pain score, changes in the time of onset of action and duration of action after the substitution of drug and side effects (such as somnolence, dizziness, and peripheral edema). In addition, the dosage was increased while paying careful attention to the side effects (titration) in 22 patients who requested a dosage increase among those whom VAS pain score of ≥25 mm remained even after the substitution. RESULTS: No significant changes were observed in VAS pain scores after the substitution of gabapentin with pregabalin. Regarding the time of onset of action and the duration of action after the substitution, the highest number of patients answered that no change occurred compared with the previous drug, followed by the patients who answered that the time of onset of action became quicker, and the duration of action became longer. The incidence of somnolence and dizziness showed no significant difference before and after the substitution, but peripheral edema showed a significant increase after the substitution. The level of side effects of both drugs was mild, and continued medication was possible. In the patient group where pregabalin dosage was increased, the VAS pain score decreased significantly compared with that before and after increase the dosage (P < 0.05). On the other hand, in nine out of 22 patients in the group where the dosage was increased, side effects appeared or were exacerbated. In two out of nine patients, it was necessary to reduce the dosage to the initial volume. CONCLUSION: It was suggested that the analgesic action of pregabalin in PHN was six times that of gabapentin in terms of effectiveness in dosage conversion. Regarding the side effects, although the incidence of the peripheral edema was higher with pregabalin compared with gabapentin, this finding is not conclusive because the present study was conducted in a small number of subjects. Although pain reduction can be expected to increase with pregabalin dosage, it is necessary to increase the dosage gradually and carefully because of exacerbation of side effects.

Prothrombotic roles of substance-P, neurokinin-1 receptors and leukocytes in the platelet-dependent clot formation in whole blood.

A number of types of non-neuronal cells including leukocytes have been confirmed to possess substance-P and its specific neurokinin-1 receptor (NK1R), while the pathophysiological roles of substance-P in these cells remain to be established. Effects of substance-P through NK1R on platelet-dependent clot formation were evaluated by using an oscillating-probe viscoelastometer. The clot signal, indicative of the clot strength in blood-derived samples, was measured after the stimulation with celite and Ca(2+). Substance-P (10 nM) increased the clot signal of whole blood obtained from healthy volunteers, especially modulating the platelet-dependent distinctive peak in traces of the signal. A NK1R antagonist Spantide (500 nM) blocked such substance-P derived change, suggesting the involvement of platelets in the action of substance-P. In contrast, substance-P did not increase the clot signal of platelet-containing but leukocyte-removed plasma. From these, we conclude that substance-P promotes platelet-dependent clot formation through NK1R, in which leukocytes appear to be involved.

Thiamylal and thiopental attenuate beta-adrenergic signaling pathway by suppressing adenylyl cyclase in rat ventricular myocytes.

The effects of intravenous anesthetics on myocytes have not been fully elucidated. To investigate the effects of various intravenous anesthetics such as fentanyl, morphine, ketamine, diazepam, midazolam, thiamylal, and thiopental on the beta-adrenergic signaling pathway, we measured isoproterenol-stimulated cyclic adenosine monophosphate (cAMP) production in freshly isolated rat ventricular myocytes. Fentanyl, morphine, ketamine, diazepam, and midazolam did not significantly affect isoproterenol-stimulated cAMP production. However, thiamylal and thiopental dose-dependently decreased cAMP production stimulated by isoproterenol or by forskolin, a direct adenylyl cyclase stimulator. In addition, we examined the role of protein kinase C (PKC) as a potential mediator of the thiamylal- or thiopental-induced effects on cAMP production using bisindolylmaleimide I, a non-specific PKC inhibitor. Bisindolylmaleimide I did not alter the inhibitory effects of thiamylal or thiopental. Thiamylal and thiopental significantly decreased isoproterenol-stimulated cAMP production by suppressing the adenylyl cyclase. We conclude that barbiturates such as thiamylal and thiopental decrease isoproterenol-stimulated cAMP production by suppressing the adenylyl cyclase through PKC-independent mechanisms.

[Combined use of intrathecal morphine and diclofenac suppository for postoperative analgesia after caesarean section].

BACKGROUND: Intrathecal morphine for postoperative analgesia after caesarean section has been used in Europe and North America, but its use is not common in Japan. METHODS: We randomized 40 parturients to two groups, given either intrathecal saline (control group) or intrathecal morphine 0.05 mg (morphine group) for caesarean section. To both groups, we gave a diclofenac suppository 50 mg every 8 hours after surgery. RESULTS: The area under curve for the visual analogue scale for pain during 24 hours after operation was significantly lower (P < 0.01) in the morphine group than the control group. In addition, the parturients who required pentazocine as a rescue analgesia was significantly fewer in the morphine group (5 parturients) than the control group (11 parturients). There was no significant difference between the two groups in the Apgar score of infants, pH in umbilical cord arterial and venous blood and the incidence of postoperative nausea and vomiting. The incidence of pruritus was significantly higher in the morphine group (11 parturients) than the control group (no parturient). CONCLUSIONS: Intrathecal morphine 0.05 mg and diclofenac suppository 50 mg given every 8 hours produced effective postoperative analgesia with minimum side effects after caesarean section.