Gabapentin enhances the morphine anti-nociceptive effect in neuropathic pain via the interleukin-10-heme oxygenase-1 signalling pathway in rats.

In the present study, we investigated the anti-inflammatory mechanisms by which gabapentin enhances morphine anti-nociceptive effect in neuropathic pain in rats and the interaction between the anti-nociceptive effects of gabapentin on morphine and the interleukin (IL)-10-heme-oxygenase (HO)-1 signal pathway in a rat model of neuropathic pain. The neuropathic pain model was induced via a left L5/6 spinal nerve ligation (SNL) in rats. The anti-nociceptive effect of gabapentin and IL-10 on morphine was examined over a 7-day period, and the effects of the anti-IL-10 and HO-1 inhibitor zinc protoporphyrin (ZnPP) on gabapentin/morphine co-injection were assessed. Drug administration was given over 7 days, and on day 8, both anti-inflammatory cytokine IL-10, a stress-induced protein HO-1 and pro-inflammatory cytokines IL-1ß, IL-6 and TNF-α were measured. Gabapentin attenuated morphine tolerance over 7 days of co-administration, and reduced the expression of pro-inflammatory cytokines but increased IL-10 and HO-1 expression. The effect of gabapentin on morphine was partially blocked using the anti-IL-10 antibody or the HO-1 inhibitor zinc protoporphyrin. Our findings indicated that the anti-nociceptive effects of gabapentin on morphine might be caused by activation of the IL-10-HO-1 signalling pathway, which resulted in the inhibition of the expression of pro-inflammatory cytokines in neuropathic pain in the rat spinal cord.

Gabapentin attenuates morphine tolerance through interleukin-10.

In this study, we examined the anti-inflammatory mechanism by which gabapentin attenuates morphine tolerance in rats. Gabapentin enhanced the antinociceptive effect of morphine and attenuated chronic morphine tolerance when administered intrathecally with morphine in naive rats. We found that a 7-day chronic intrathecal injection of morphine increased the expression of proinflammatory cytokines and decreased interleukin-10 (IL-10) levels in the rat spinal cord. These changes were minimized when gabapentin was combined with morphine. In addition, the effects of gabapentin were reversed by coadministration of the anti-IL-10 antibody. Our findings indicate that enhancement of the antinociceptive effect of morphine by gabapentin may occur through upregulation of the anti-inflammatory cytokine IL-10 and inhibition of proinflammatory cytokines in the rat spinal cord.

Peripheral nerve adjustment for postherpetic neuralgia: a randomized, controlled clinical study.

OBJECTIVE: To observe the therapeutic effect of peripheral nerve adjustment for the treatment of postherpetic neuralgia (PHN). METHODS: One hundred and two patients with PHN were randomly assigned to three groups; the control group (A), the experimental group (B), which was subjected to peripheral nerve adjustment, and patients who received a sham peripheral nerve adjustment, thus serving as a positive control group (C). The patients' Visual Analogue Scale (VAS) and total oral rescue dosage for pain management were recorded at days 1, 3, 7, 14, and 28 following treatment. Quality of life (QOL), 36-Item Short-Form Health Survey (SF-36), and side effects were recorded following treatment. RESULTS: We observed that the average VAS score was significantly lower in the treatment group (B) than in the control groups A and C following treatment (P < 0.05). In addition, the QOL and SF-36 scores for group B improved substantially following treatment compared to groups A and C, and this effect was maintained up to 180 days after treatment (P < 0.05). The average dosage of pain medication was also lower in group B, compared to groups A and C, following treatment (P < 0.05). CONCLUSIONS: We conclude that peripheral nerve adjustment can relieve PHN pain and improve patients' quality of life. The possible mechanisms involved may include the reduction of both peripheral and central sensitization, the modulation of nerve plasticity, and an increase in endogenous analgesic molecules.

Lipid metabolism disturbances and AMPK activation in prolonged propofol-sedated rabbits under mechanical ventilation.

AIM: To explore the mechanisms underlying the propofol infusion syndrome (PRIS), a potentially fatal complication during prolonged propofol infusion. METHODS: Male rabbits under mechanical ventilation through endotracheal intubation were divided into 3 groups (n=6 for each) that were sedated with 1% propofol (Group P), isoflurane (Group I) or isoflurane while receiving 10% intralipid (Group II), respectively. Blood biochemical parameters were collected at 0, 6, 12, 18, 24 and 30-36 h after the initiation of treatments. The hearts were removed out immediately after the experiments, and the level of tumor necrosis factor (TNF)-α in the hearts were studied using immunohistochemistry. AMP-activated protein kinase (AMPK) and phospho-AMPK in the hearts were assessed using Western blotting. RESULTS: The mortality rate was 50% in Group P, and 0% in Groups I and II. The serum lipids and liver function indices in Group P were significantly increased, but moderately increased in Group II. Significant decreases in these indices were found in Groups I. All the groups showed dramatically increased release of creatine kinase (CK). Intense positive staining of TNF-α was found in all the heart samples in Group P, but only weak and neglectful staining was found in the hearts from Group II and Group I, respectively. AMPK phosphorylation was significantly increased in the hearts of Group P. CONCLUSION: Continuous infusion of large dose of propofol in rabbits undergoing prolonged mechanical ventilation causes hyperlipidemia, liver dysfunction, increased CK levels, AMPK activation and myocardial injury. The imbalance between energy demand and utilization may contribute to PRIS.

A comparative study of the mortality rate of rats receiving a half lethal dose of fat intravenously: under general anaesthesia versus under spinal anaesthesia.

BACKGROUND: There is no data that demonstrates what anaesthesia is suitable for patients who have a high risk of fat embolism syndrome (FES). We investigated the mortality rates of rats that received a half lethal dose (LD(50)) of fat by intravenous injection after induction of general or spinal anaesthesia. METHODS: An LD(50) of fat for rats was determined by using a toxicological method. Three hundred and seventy five rats were randomly assigned to receive general anaesthesia (group GA, n=125), or spinal block (group SA, n=125), or no anaesthesia (group C, n=125). The rats were injected with the LD(50) of fat at 20 min after anaesthesia induction. The mortality rates were recorded at 2, 8, 12, and 24h after fat injection. RESULTS: The LD(50) of fat was 0.706 ml/kg and its 95% CI was 0.622 ml/kg-0.801 ml/kg. The mortality rate was lower in the group GA than in the group SA (p<0.01), whilst there was no statistical difference between the group SA and the group C (p=0.442). CONCLUSION: It is feasible to assess the efficacy of various treatments for FES by comparing the mortality rates of animals after injection of an LD(50) of fat. The mortality rate of rats was lower when FES was induced under general anaesthesia than under spinal anaesthesia which implies that general anaesthesia is superior to spinal anaesthesia for patients who have a high risk of FES.

Ultrasound-guided continuous femoral nerve block for analgesia after total knee arthroplasty: catheter perpendicular to the nerve versus catheter parallel to the nerve.

BACKGROUND AND OBJECTIVES: This study tested the hypothesis that, in continuous femoral nerve block (CFNB) under ultrasound guidance, placing a catheter perpendicular to the nerve can shorten the time of catheter insertion while providing a similar quality of analgesia compared with placing a catheter parallel to the nerve. METHODS: Fifty patients undergoing total knee arthroplasty were randomly assigned to receive ultrasound-guided CFNB either with the catheter parallel to the nerve technique (parallel group, n = 25) or with the catheter perpendicular to the nerve technique (perpendicular group, n = 25). Patient-controlled morphine analgesia pumps were available to all the patients after surgery. The time of catheter insertion, failure rates, pain scores, morphine consumption, nausea and vomiting, and maximal degree of knee flexion were recorded. RESULTS: The time of catheter insertion was shorter in the perpendicular group than in the parallel group (12 +/- 3 versus 22 +/- 6 mins, P < 0.01). Failed catheter insertion occurred in 3 (12%) of 25 patients in the parallel group and in none of 25 patients in the perpendicular group (P = 0.2347). There were no significant differences in pain scores, opioid consumption, incidence of nausea and vomiting, and maximal degree of knee flexion between the 2 groups. CONCLUSIONS: In CFNB under ultrasound guidance, using the catheter perpendicular to the nerve technique can shorten the time of catheter insertion while providing a similar quality of analgesia after total knee arthroplasty as compared with the catheter parallel to the nerve technique.

[Diagnostic value of 128-slice CT coronary angiography in comparison with invasive coronary angiography].

OBJECTIVE: To observe the diagnostic value of non-invasive 128-slice computed tomography coronary angiography (CTA) in comparison with invasive coronary angiography. METHODS: 128-slice CTA and invasive coronary angiography were performed in 78 unselected consecutive patients (63 patients with suspected coronary artery disease and 15 patients with previous coronary stenting, 56 males, mean age 61 +/- 10 years) and > 50% reduction of minimal lumen diameter was defined as significant coronary stenosis. RESULTS: Fifty-eight out of 879 segments (7%) from CTA were not assessable because of irregular rhythm, vessel calcification or tachycardia. Compared with invasive coronary angiography, segment-based analysis from the 821 segments showed the sensitivity by CTA was 87%, specificity 97%, PPV 83% and NPV 97%. Four out of 22 stents implanted in 15 patients were not assessable by CTA because of poor image quality. Compared with invasive coronary angiography, the sensitivity of diagnosing in-stent restenosis by CTA was 100%, specificity 77%, PPV 63% and NPV 100% for the remaining 18 stents. CONCLUSIONS: One hundred and twenty-eight-slice CTA has a high accuracy for detecting coronary artery disease and in-stent restenosis after coronary stenting and could be considered as a valuable noninvasive technique for screening coronary artery disease in suspected patients.

TTX-R Na+ current-reduction by celecoxib correlates with changes in PGE(2) and CGRP within rat DRG neurons during acute incisional pain.

The present study was undertaken to investigate whether celecoxib could regulate the tetrodotoxin-resistant (TTX-R) sodium channel current in rat dorsal root ganglia (DRG) and whether prostaglandin E2 (PGE2) and calcitonin gene-related protein (CGRP) were involved in celecoxib's analgesia during acute incisional pain. Seventy-five rats were randomly allocated into three groups. Group A was the control group receiving a placebo (sugar pill) 1 h before and 12 h after surgery (right hind paw incisional pain). Group B was the test group receiving celecoxib 30 mg/kg orally 1 h before and 12 h after surgery. Group C was the naive group receiving a sham operation. The changes in the mechanical withdrawal thresholds, PGE2 and CGRP concentration in incisional paw tissue and DRG, and total TTX-R sodium channel current density in small DRG neurons were investigated 1 h before the operation and 2 h, 6 h, 12 h, 24 h, 48 h and 96 h after the operation. The results showed both of a decrease in mechanical withdrawal thresholds and an increase of TTX-R sodium channel current density in DRG neurons in group B were significantly lower than those of group A at 24 h and 48 h after the operation (P<0.05). The increase in PGE2 and CGRP concentrations at incisional paw tissue and DRG neurons in group B were lower than those of groups A at 24 h and 48 h after the operation (P<0.05). This study indicates that: 1) celecoxib can inhibit TTX-R sodium channel current density in rat DRG neurons; 2) PGE2 and CGRP participate in celecoxib's analgesic effect on acute incisional pain.