Silymarin decreases connective tissue growth factor to improve liver fibrosis in rats treated with carbon tetrachloride.

Silymarin is an herbal product showing potential as protection against hepatic disorders. In an attempt to develop the agent for the treatment of hepatic fibrosis, we screened the effects of silymarin on a rat model of hepatic fibrosis induced by carbon tetrachloride (CCl4). Intraperitoneal administration of CCl4 to rats for 8 weeks not only increased the plasma levels of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) but also induced a marked increase in the formation of hepatic fibrosis. Moreover, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were also reduced in the liver of rats treated with CCl4. Oral administration of silymarin (200 mg/kg, three times daily), in parallel, decreased the plasma levels of GOT and GPT. Furthermore, in addition to the improvement of hepatic fibrosis, the hepatic levels of hydroxyproline and connective tissue growth factor (CTGF) were both markedly decreased by silymarin. Silymarin also elevated the activities of SOD and GPx in liver isolated from CCl4-treated rats. The results suggest that oral administration of silymarin protects against CCl4-induced hepatic fibrosis in rats, likely due to the decrease in fibrotic parameters such as CTGF.

Tianeptine reduces morphine antinociceptive tolerance and physical dependence.

Long-term use of morphine can cause neuronal dystrophic changes in specific areas of the brain. These changes may underlie the mechanism for developing morphine antinociceptive tolerance and physical dependence. We evaluated the effect of tianeptine, an antidepressant with prominent neuroprotective and neuroplastic properties, on the development of morphine antinociceptive tolerance and physical dependence. Male C57BL/6 mice were rendered tolerant to or dependent on morphine by subcutaneously injecting them with morphine (10 mg/kg) and intraperitoneally with saline or tianeptine (1, 3, or 5 mg/kg) twice daily for 6 days. The mice were given a daily tail-flick test 1 h after the first morphine injection to evaluate the development of their tolerance to morphine antinociception. To evaluate their physical dependence on morphine, 3 h after the final morphine injection on day 6, naloxone-HCl-precipitated (2 mg/kg, intraperitoneally) withdrawal symptoms were counted for 30 min, and body weight was checked 1 h after the naloxone injection. Tianeptine per se produced no antinociception, neither did it modify the antinociception produced by morphine, nor did it evoke the behavioral responses different from those in the saline controls. The combination of tianeptine with morphine significantly reduced the development of morphine antinociceptive tolerance and suppressed the incidence of naloxone-precipitated withdrawal symptoms. We conclude that tianeptine is an effective inhibitor of morphine-induced antinociceptive tolerance and physical dependence in mice. Our results would imply that comedication with tianeptine and morphine might benefit those who need long-term morphine treatment.

Amitriptyline pretreatment preserves the antinociceptive effect of morphine in pertussis toxin-treated rats by lowering CSF excitatory amino acid concentrations and reversing the downregulation of glutamate transporters.

This study was designed to investigate the effect of acute intrathecal (i.t.) injection of amitriptyline (AMI) on the antinociceptive effect of morphine in rats treated with pertussis toxin (PTX). Male Wistar rats were implanted with an i.t. catheter for drug injection and some were implanted with an additional microdialysis probe used for CSF dialysate collection and measurement of excitatory amino acids (EAAs). The expression of glutamate transporters (GTs) in the spinal cord dorsal horn was also measured. A tail-flick test was performed and CSF dialysate was collected as the baseline-B value (day 0) before PTX (1 microg, i.t.) injection and at 4 days after PTX injection, but before drug challenge as the baseline-P value (day 4), and at 30, 60, 90, and 120 min after drug challenge on day 4. The baseline-P tail-flick latencies were significantly lower than the baseline-B values. In PTX-treated rats (day 4), morphine (10 microg, i.t.) did not produce an antinociceptive effect, but this was retained by acute AMI (15 microg, i.t.) pretreatment 30 min before morphine injection. In addition, concentrations of glutamate and aspartate were higher in baseline-P dialysates than in baseline-B dialysates, and the expression of the GTs (GLT-1, GLAST, and EAAC1) was downregulated by PTX treatment. Acute injection of PTX-treated rats with either AMI (15 microg, i.t.) or morphine (10 microg, i.t.) alone had no significant effect on CSF EAA concentrations and GT expression. In contrast, AMI (15 microg, i.t.) pretreatment followed 30 min later by morphine (10 microg, i.t.) injection inhibited the increase in EAA concentrations and reversed the downregulation of all three GTs. Our results show that AMI preserves the antinociceptive effect of morphine in PTX-treated rats. The mechanisms involve suppression of the increase in EAA concentrations in spinal CSF dialysates and reversion of GT expression in PTX-treated rats.

The prophylactic effect of haloperidol plus dexamethasone on postoperative nausea and vomiting in patients undergoing laparoscopically assisted vaginal hysterectomy.

BACKGROUND: Haloperidol, a major tranquilizer, has been found to have a potent antiemetic effect on postoperative nausea and vomiting (PONV), but the prophylactic effect of haloperidol plus dexamethasone on PONV has not been evaluated. We evaluated the prophylactic effect of haloperidol plus dexamethasone to either given alone, placebo or droperidol on PONV in patients undergoing a laparoscopic-assisted vaginal hysterectomy. METHODS: Four hundred adult women (n = 80 in each of five groups) scheduled for a laparoscopic-assisted vaginal hysterectomy were enrolled in a randomized, double-blind, placebo, and positive-control study. Fifteen minutes after the induction of anesthesia, patients received an i.v. injection of either saline (group S), droperidol 1.25 mg (group D), haloperidol 2 mg (group H), dexamethasone 5 mg (group Dx), or haloperidol 2 mg plus dexamethasone 5 mg (group H + Dx) to prevent PONV. The occurrence of PONV and medication-related side effects were recorded. RESULTS: The incidences of PONV (0-24 h) in the D (36%), H (37%), Dx (38%), and H + Dx (19%) groups were significantly lower than in the S group (65%; P < 0.05 for each comparison). The H + Dx group had the lowest incidence of PONV (19%; P < 0.05 for each comparison) of the five study groups. No differences were found between the D, H, and Dx groups. Also, no differences were found among the five groups in the side effects of QT prolongation, intensity of postoperative pain, level of sedation, and occurrence of extra-pyramidal symptoms. CONCLUSION: Prophylactic haloperidol 2 mg plus dexamethasone 5 mg produced a greater reduction in the incidence of PONV than did either drug used alone, placebo or droperidol without increasing perioperative adverse outcomes.

Spinal sensory and motor blockade by intrathecal doxylamine and triprolidine in rats.

OBJECTIVES: The aim of this experiment was mainly to examine the effects of intrathecally injected doxylamine and triprolidine, two antihistamine drugs spinal motor and sensory functions. METHODS: After intrathecally injecting the rats with five different doses, the dose-response curves of spinal sensory and motor block with doxylamine and triprolidine were constructed. In comparison with the local anaesthetic mepivacaine, the quality and duration of spinal anaesthesia with doxylamine or triprolidine were conducted. KEY FINDINGS: Doxylamine, mepivacaine and triprolidine elicited spinal motor and sensory (nociception and proprioception) blockades in a dose-dependent fashion. On the ED50 (50% effective dose) basis, the rank order of drug potency was triprolidine > mepivacaine > doxylamine (P < 0.05) at provoking spinal motor, proprioceptive and nociceptive blockades. On the equianaesthetic doses (ED25 , ED50 and ED75 ), the duration of spinal anaesthesia with doxylamine was longer (P < 0.01) than that with mepivacaine or triprolidine. Moreover, doxylamine or triprolidine displayed greater potency (ED50 ) (P < 0.05) and duration (P < 0.05) of sensory block over motor block. CONCLUSIONS: Doxylamine or triprolidine produces a dose-dependent effect of spinal motor and sensory block. Triprolidine with a better nociception-selective action over motor block has a better potency than mepivacaine or doxylamine. Doxylamine and triprolidine produce longer durations than mepivacaine.

Dextromethorphan or dextrorphan have a local anesthetic effect on infiltrative cutaneous analgesia in rats.

BACKGROUND: Dextromethorphan blocks sodium channels, the site of action of local anesthetics. In this study we evaluated whether dextromethorphan has a local anesthetic effect. METHODS: We administered dextromethorphan and its active metabolite--dextrorphan, and lidocaine subcutaneously to rats and tested them for cutaneous anesthesia. Drug-drug interactions and systemic safety indices (LD50s/ED50s) were also evaluated. RESULTS: Dextromethorphan and dextrorphan had a local anesthetic effect after cutaneous infiltration. The ranking of potencies was dextromethorphan > dextrorphan > lidocaine (P < 0.01 for each comparison). A combination of dextromethorphan or dextrorphan with lidocaine produced an additive effect. Dextromethorphan and dextrorphan had 2.4- and 1.9-fold higher system safety indices than did lidocaine. CONCLUSION: Dextromethorphan and dextrorphan were more potent local anesthetics than lidocaine, but with higher systemic safety indices. Coadministration of dextromethorphan or dextrorphan with lidocaine produced an additive effect.

The cutaneous analgesic effect of class I antiarrhythmic drugs.

BACKGROUND: Local anesthetics, when applied to nerves, produce reversible loss of sensation by blocking Na+ channels. Because all Class I antiarrhythmic drugs are Na+ channel blockers, theoretically, they may have local anesthetic effects. In this study, we sought to define the cutaneous local anesthetic actions of three Class I antiarrhythmic drugs. METHODS: Using a subcutaneous infiltration model in rats, the potencies and durations of action of quinidine (Class IA), mexiletine (IB), and flecainide (IC) were determined and compared with the actions of lidocaine and bupivacaine. Saline injection was used as control. RESULTS: Three Class I antiarrhythmic drugs produced a dose-related cutaneous analgesia with ranking of potencies of bupivacaine > flecainide > quinidine > mexiletine > lidocaine (P < 0.05 for the differences among drugs). On an equipotent basis, the ranking of durations of action was flecainide > quinidine and bupivacaine > mexiletine and lidocaine (P < 0.05 for the differences among drugs). CONCLUSION: Three Class I antiarrhythmic drugs, quinidine (IA), mexiletine (IB), and flecainide (IC) have a local anesthetic effect on cutaneous analgesia.

Isobolographic analysis of the cutaneous antinociceptive interaction between bupivacaine co-injected with serotonin in rats.

BACKGROUND: The aim of this experiment was to investigate a long-lasting local anesthetic bupivacaine combined with serotonin at inducing cutaneous antinociception. METHODS: The skin antinociception, characterized by an inhibition of the cutaneous trunci muscle reflex (CTMR) following the pinprick on the dorsal skin of rats, was evaluated. The cutaneous antinociceptive effects of bupivacaine alone, serotonin alone, or bupivacaine co-injected with serotonin in a dose-dependent fashion were constructed, while the drug-drug interactions were evaluated by isobologram. RESULTS: Subcutaneous serotonin, as well as the local anesthetic bupivacaine provoked dose-related cutaneous antinociception. On an equipotent basis (50% effective dose [ED50]), the relative potency was bupivacaine (0.43 [0.37-0.50] µmol)>serotonin (1.27 [1.15-1.40] µmol) (p<0.01). At the equi-anesthetic doses (ED75, ED50 and ED25), the duration of bupivacaine was similar to that of serotonin at producing cutaneous antinociceptive effects. Co-administration of bupivacaine and serotonin displayed a synergistic antinociception. CONCLUSIONS: The preclinical data demonstrated that serotonin is less potent in eliciting cutaneous antinociceptive effects but has the similar duration of action, compared with bupivacaine. We also found a more significant depth of the sensory block with bupivacaine+serotonin than bupivacaine alone.

Dextromethorphan, 3-methoxymorphinan, and dextrorphan have local anaesthetic effect on sciatic nerve blockade in rats.

Dextromethorphan has been used as an antitussive for more than 40 years and is considered a drug with a good margin of safety. The aim of the study was to evaluate whether dextromethorphan and its metabolites--3-methoxymorphinan and dextrorphan--had local anaesthetic effects. Using a method of sciatic nerve blockade in rats, the potencies and durations of actions of dextromethorphan and its metabolites on sciatic nerve blockades of motor function, proprioception, and nociception were evaluated. Lidocaine was used as control. We found that dextromethorphan and its metabolites produced dose-related local anaesthetic effects on sciatic nerve blockades of motor function, proprioception, and nociception. The ranks of potencies were lidocaine>dextromethorphan>3-methoxymorphinan>dextrorphan (P<0.01 for each comparison). Under an equi-potent basis, dextrorphan and 3-methoxymorphinan had durations of actions longer than that of lidocaine (P<0.05 for each comparison). Co-administration of dextromethorphan or its metabolites with lidocaine produced an additive effect on sciatic nerve blockades. In conclusion, dextromethorphan and its metabolites - 3-methoxymorphinan and dextrorphan- had a local anaesthetic effect on sciatic nerve blockades of motor function, proprioception and nociception with durations of actions longer than that of lidocaine. Co-administration of dextromethorphan and its metabolites produced an additive effect on sciatic nerve blockades.

Concerns about reporting pain and using analgesics among taiwanese postoperative patients.

UNLABELLED: The purpose of this study was to explore concerns about reporting pain and using analgesics and also to explore whether these concerns were related to the dosage of analgesics used among Taiwanese postoperative patients with pain. The three subscales receiving the highest scores on the BQT-S were time interval, tolerance, and injection. Patients who had hesitated to report pain had significantly higher scores on time interval, fear of tolerance, wound healing, fear of distracting one's physician from treating the disease, a desire to be a good patient, fatalism, and the total BQT-S score than those patients who had not hesitated to report pain. Patients who had hesitated to take medications reported significantly higher scores on time interval, wound healing, fear of distracting one's physician from treating the disease, a desire to be a good patient, fatalism, and the total BQT-S score than did those patients who had not hesitated to use analgesics. BQT-S scores were significant positively in relation to pain intensity and pain interference but were negatively related to dosage of analgesics used. PERSPECTIVE: This study documented postoperative patient concerns about reporting pain and using analgesics and their impact on adequate management of postoperative pain. Education about pain management for patients and clinicians could be an effective intervention to improve the management of postoperative pain in Taiwan.

Novel depots of buprenorphine prodrugs have a long-acting antinociceptive effect.

An analgesic with a prolonged duration may be desirable in patients with long-lasting pain. In this study, we evaluated the antinociceptive effects and durations of action of three novel depots of buprenorphine esters buprenorphine propionate, enanthate, and decanoate given by IM injection, in rats. The pharmacokinetic profiles of buprenorphine in blood after IM injection of these depots were also evaluated. Antinociception was evaluated using the plantar test. Buprenorphine concentrations in blood were assayed using high-performance liquid chromatography. We found that the traditional form of buprenorphine HCl (in saline) produced a dose-related antinociceptive effect. A dose of 0.6 micromol/kg buprenorphine HCl (in saline) produced a significant antinociceptive effect lasting 5 h. The same dose of buprenorphine base, propionate, enanthate, and decanoate (in oil) also produced a significant antinociceptive effect with longer durations of action of 26, 28, 52, and 70 h, respectively. The pharmacokinetic studies demonstrated that all the buprenorphine esters were prodrugs of buprenorphine. We conclude that the novel depots of buprenorphine prodrugs: buprenorphine propionate, enanthate, and decanoate produced a long-acting antinociceptive effect after IM injection in rats.

Intrathecal rimantadine induces motor, proprioceptive, and nociceptive blockades in rats.

The purpose of the experiment was to evaluate the local anesthetic effect of rimantadine in spinal anesthesia. Rimantadine in a dose-dependent fashion was constructed after intrathecally injecting the rats with four different doses. The potency and duration of rimantadine were compared with that of the local anesthetic lidocaine at producing spinal motor, nociceptive, and proprioceptive blockades. We demonstrated that intrathecal rimantadine dose-dependently produced spinal motor, nociceptive, and proprioceptive blockades. On the 50% effective dose (ED50) basis, the ranks of potencies at inducing spinal motor, nociceptive, and proprioceptive blockades was lidocaine>rimantadine (P<0.01). Rimantadine exhibited more nociceptive block (ED50) than motor block (P<0.05). At equi-anesthetic doses (ED25, ED50, and ED75), the spinal block duration produced by rimantadine was longer than that produced by lidocaine (P<0.01). Furthermore, rimantadine (26.52µmol/kg) prolonged the nociceptive nerve block more than the motor block (P<0.001). Our preclinical data showed that rimantadine, with a more sensory-selective action over motor block, was less potent than lidocaine. Rimantadine produced longer duration in spinal anesthesia when compared with lidocaine.

Therapeutic Ultrasound and Treadmill Training Suppress Peripheral Nerve Injury-Induced Pain in Rats.

BACKGROUND: Although evidence suggests that therapeutic ultrasound (TU) in combination with treadmill training (TT) suppresses nerve injury-associated pain, the molecular mechanisms for this action are not clear. OBJECTIVE: The purpose of this research was to study the possible beneficial effects of TU and TT, alone and in combination, on 2 clinical indicators of neuropathic pain and correlate these findings with changes in inflammatory mediators within the spinal cord. Our experimental model used the well-known chronic constriction injury (CCI) of the rat sciatic nerve. DESIGN: This was an experimental study. METHODS: Each group contained 10 rats. Group 1 underwent only the CCI procedure. Group 2 underwent a sham operation where the sciatic nerve was exposed but not ligated. Group 3 had the sham operation followed by both TT and TU. Groups 4, 5, and 6 underwent the CCI procedure followed by TT alone, TU alone, and both the TT and TU interventions, respectively. Heat and mechanical sensitivity, interleukin-6 (IL-6), interleukin-10 (IL-10), and ionized calcium binding adaptor molecule 1 (Iba1) were evaluated. RESULTS: Compared with group 1 animals, TT or TU, or both, produced smaller decreases in mechanical withdrawal threshold and heat withdrawal latencies. The combination of TT and TU was more effective than either treatment alone. In addition, rats that received these treatments did not express the upregulation of IL-6 and Iba1 in their spinal cords on postoperative days 14 and 28, as was found in the group 1 animals. LIMITATIONS: These experimental findings may not be generalizable to humans. CONCLUSIONS: The combination of TU and TT reduces neuropathic pain more than either modality alone. This beneficial effect appears related to downregulation of proinflammatory IL-6 and Iba1, while upregulating the anti-inflammatory IL-10.

Cutaneous synergistic analgesia of bupivacaine in combination with dopamine in rats.

The main goal of the study was to investigate the interaction between bupivacaine and dopamine on local analgesia. After the blockade of the cutaneous trunci muscle reflex (CTMR) responses, which occurred following the drugs were subcutaneously injected in rats, the cutaneous analgesic effect of dopamine in a dosage-dependent fashion was compared to that of bupivacaine. Drug-drug interactions were evaluated by isobolographic methods. We showed the dose-dependent effects of dopamine on infiltrative cutaneous analgesia. On the 50% effective dose (ED50) basis, the rank of drug potency was bupivacaine (1.99 [1.92-2.09] µmol/kg) greater than dopamine (190 [181-203] µmol/kg) (P<0.01). At the equianalgesic doses (ED25, ED50, and ED75), dopamine elicited a similar duration of cutaneous analgesia compared with bupivacaine. The addition of dopamine to the bupivacaine solution exhibited a synergistic effect. Our pre-clinical data showed that dopamine produced a dose-dependent effect in producing cutaneous analgesia. When compared with bupivacaine, dopamine produced a lesser potency with a similar duration of cutaneous analgesia. Dopamine added to the bupivacaine preparation resulted in a synergistic analgesic effect.

Intrathecal amantadine for prolonged spinal blockade of sensory and motor functions in rats.

We aimed to compare the hypothesized local anesthetic action of amantadine (1-adamantanamine) with that of the known local anesthetic mepivacaine. Motor, proprioceptive, and nociceptive functions were evaluated in rats after intrathecal administration. Amantadine elicited spinal anesthesia in a dose-related fashion and produced a better sensory-selective action over motor blockade (P < 0.01). On the 50% effective dose (ED50 ) basis, the rank of potency on spinal motor, proprioceptive, and nociceptive block was mepivacaine > amantadine (P < 0.01 for the differences). Amantadine (63.5 µmol/kg) and mepivacaine (7.1 µmol/kg) produced complete spinal block of motor function, proprioception, and nociception. On an equipotent basis (ED25 , ED50 , and ED75 ), the duration of amantadine was longer (P < 0.01) than that of mepivacaine on spinal motor, proprioceptive, and nociceptive block. Our preclinical data demonstrated that amantadine was less potent than mepivacaine at producing spinal anesthesia. The spinal block duration produced by amantadine was greater than that produced by mepivacaine. Both amantadine and mepivacaine produced a markedly nociceptive-specific blockade.

Simultaneous determination of buprenorphine and its prodrug, buprenorphine propionate, by high-performance liquid chromatography with fluorescence detection: application to pharmacokinetic studies in rabbits.

A rapid, sensitive, precise and accurate high-performance liquid chromatographic assay with fluorescence detection was developed for the simultaneous determination of buprenorphine and buprenorphine propionate in human and animal blood. Buprenorphine propionate was also proven to be a prodrug of buprenorphine. It was comprised of only a one-step extraction procedure with ethyl acetate and normal-phase chromatography on a Betasil Silica column. The recoveries of buprenorphine and buprenorphine propionate were above 84%. Calibration graphs were linear for buprenorphine over the concentration range 2-1500 ng/ml and for buprenorphine propionate over the concentration range 20-1500 ng/ml with a coefficient of variation, both within- and between-day, or less than 10% at any level. The limits of quantitation of buprenorphine and buprenorphine propionate in human or animal blood were 2.0 and 20 ng/ml, respectively, based on a single-to-noise ratio of 3. The method has been successfully applied to pharmacokinetic studies of buprenorphine and buprenorphine propionate in rabbits. The results demonstrated that buprenorphine propionate was rapidly and totally converted to its parent drug, buprenorphine, following intravenous administration. Buprenorphine propionate is a prodrug of buprenorphine.

Chlorpheniramine produces spinal motor, proprioceptive and nociceptive blockades in rats.

This study aimed to assess the local anesthetic effects of chlorpheniramine in spinal anesthesia and is compared with mepivacaine, a widely-used local anesthetic. Spinal anesthesia with chlorpheniramine and mepivacaine was constructed in a dosage-dependent fashion after the rats were injected intrathecally. The spinal block effect of chlorpheniramine in motor function, nociception, and proprioception was compared to that of mepivacaine. We revealed that intrathecal chlorpheniramine and mepivacaine exhibited a dose-dependent spinal block of motor function, nociception, and proprioception. On the 50% effective dose (ED50) basis, the ranks of potencies in motor function, nociception, and proprioception were chlorpheniramine>mepivacaine (P<0.01 for the differences). On the equianesthetic basis (ED25, ED50, ED75), the duration of spinal anesthesia with chlorpheniramine was greater than that of mepivacaine (P<0.01 for the differences). Instead of mepivacaine, chlorpheniramine produced a greater duration of sensory blockade than the motor blockade. These preclinical data showed that chlorpheniramine has a better sensory-selective action over motor block to produce more potent and long-lasting spinal anesthesia than mepivacaine.

Effects of Walking on Quality of Life Among Lung Cancer Patients: A Longitudinal Study.

BACKGROUND: Walking is typically the preferred form of physical activity among lung cancer patients. Physical activity can promote and maintain the health of such patients. OBJECTIVE: We examined how walking affected the quality of life (QOL) of lung cancer patients, evaluating the factors that predicted changes in walking during a 6-months study. METHODS: This study involved a longitudinal and correlational design, and the instruments comprised the Godin Leisure-Time Exercise Questionnaire, the Functional Assessment of Cancer Therapy-Lung Cancer, and social support and self-efficacy scales. RESULTS: In total, 107 patients were evaluated for 6 months; the results indicated that the patients completed approximately 217 to 282 minutes of walking per week. The data demonstrated that the frequency of walking exercise decreased or stopped among 36% patients during the 6-month study. A generalized estimating equation analysis indicated significant differences between the Functional Assessment of Cancer Therapy-Lung Cancer scores and levels of physical and functional well-being among the lung cancer patients who did and did not engage in walking. Social support, self-efficacy, and patient treatment status can be used to predict the change in walking among lung cancer patients. CONCLUSION: Patient QOL can be improved by engaging in walking exercise for 6 months. Regarding lung cancer patients, social support and self-efficacy are the key factors in maintaining walking exercise. IMPLICATIONS FOR PRACTICE: Integrating psychological strategies may be required to strengthen the positive effects of walking exercise on the QOL of lung cancer patients.

Transcutaneous electrical nerve stimulation attenuates postsurgical allodynia and suppresses spinal substance P and proinflammatory cytokine release in rats.

BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is often used for management of chronic pain. OBJECTIVE: The purpose of this study was to investigate whether TENS altered postincisional allodynia, substance P, and proinflammatory cytokines in a rat model of skin-muscle incision and retraction (SMIR). DESIGN: This was an experimental study. METHODS: High-frequency (100-Hz) TENS therapy began on postoperative day 3 and was administered for 20 minutes daily to SMIR-operated rats by self-adhesive electrodes delivered to skin innervated via the ipsilateral dorsal rami of lumbar spinal nerves L1-L6 for the next 27 days. The expressions of substance P, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1beta (IL-1ß) in the spinal cord and mechanical sensitivity to von Frey stimuli (4g and 10g) were evaluated. RESULTS: The SMIR-operated rats displayed a marked hypersensitivity to von Frey stimuli on postoperative day 3. In contrast to the SMIR-operated rats, SMIR-operated rats after TENS administration showed a quick recovery of mechanical hypersensitivity. On postoperative days 3, 16, and 30, SMIR-operated rats exhibited an upregulation of substance P and cytokines (TNF-α, IL-6, and IL-1ß) in the spinal cord, whereas SMIR-operated rats after TENS therapy inhibited that upregulation. By contrast, the placebo TENS following SMIR surgery did not alter mechanical hypersensitivity and the levels of spinal substance P, TNF-α, IL-6, and IL-1ß. LIMITATIONS: The experimental data are limited to animal models and cannot be generalized to postoperative pain in humans. CONCLUSIONS: The results revealed that TENS attenuates prolonged postoperative allodynia following SMIR surgery. Increased levels of spinal substance P and proinflammatory cytokines, activated after SMIR surgery, are important in the processing of persistent postsurgical allodynia. The protective effect of TENS may be related to the suppression of spinal substance P and proinflammatory cytokines in SMIR-operated rats.

Relationships of Circadian Rhythms and Physical Activity With Objective Sleep Parameters in Lung Cancer Patients.

BACKGROUND: Lung cancer patients undergo various treatments leading to sleep problems, rest-activity circadian rhythms disruption, and reduced levels of physical activity. It is important to understand the relationships among these variables. Appropriate interventions can possibly be implemented to improve sleep quality in lung cancer patients. OBJECTIVE: The objective of this study was to examine the relationships of circadian rhythms and physical activity with objective sleep parameters in 106 of Taiwanese lung cancer patients. METHODS: This study used a cross-sectional design. The instruments included an actigraph to measure the objective sleep parameters (total sleep time [TST], sleep efficiency, and sleep-onset latency [SOL]), rest-activity circadian rhythms (r24 [24-hour autocorrelation coefficient] and I < O [in-bed less than out-of-bed dichotomy index]), and physical activity frequency (UP activity mean). The daily physical activity amount in minutes was measured by the Bouchard 3-day physical activity record. RESULTS: Patients performing light-intensity physical activity of 295 min/d or greater had better values for the TST, sleep efficiency, SOL, r24, and I < O than those performing less than 295 min/d (all P < .05). Significant predictors of the TST included age (ß = -.31), I < O (ß = .32), and UP activity mean (ß = -.42). Predictors of the SOL included current treatment (ß = .20), I < O (ß = -.28), UP activity mean (ß = .51), and 24-hour light-activity minutes (ß = -.23). CONCLUSIONS: Marked circadian rhythms and adequate light-intensity physical activity may improve sleep quality in lung cancer patients. IMPLICATIONS FOR PRACTICE: Adequate light-intensity physical activity can be an effective intervention to improve sleep quality in lung cancer patients.