Effects of bupivacaine and tetrodotoxin on carrageenan-induced hind paw inflammation in rats (Part 1): hyperalgesia, edema, and systemic cytokines

BACKGROUND: Local anesthetics exert antiinflammatory actions. To elucidate potential mechanisms, the authors examined effects of bupivacaine or tetrodotoxin, administered to rats by ipsilateral or contralateral sciatic blockade or systemically, on carrageenan-induced hind paw hyperalgesia, edema, and stimulated cytokine production in circulating blood cells. METHODS: Twelve groups of rats (n = 9-12) received injections in three sites: (1) right or left hind paw (carrageenan or saline), (2) left sciatic block, and (3) systemically (subcutaneously in the upper back). Sciatic and systemic injections were performed with epinephrine plus bupivacaine, tetrodotoxin, or saline; injections were repeated 6 h later. Fifteen hours later, hyperalgesia and/or sensory and motor block were assessed behaviorally, and paw edema was quantified by magnetic resonance imaging. Stimulated production of tumor necrosis factor alpha, interleukin 10, and interleukin 1beta in whole blood cultures was measured by enzyme-linked immunosorbent assay. RESULTS: Either ipsilateral or contralateral sciatic blocks using either bupivacaine or tetrodotoxin reduced carrageenan-induced edema and hyperalgesia. Systemic bupivacaine and tetrodotoxin were ineffective in preventing edema and hyperalgesia. Bupivacaine was effective in suppressing systemic tumor necrosis factor alpha and interleukin 1beta by all three routes, whereas tetrodotoxin was ineffective by all three routes. CONCLUSION: Bupivacaine and tetrodotoxin, via a contralateral or ipsilateral sciatic block, attenuate local inflammatory edema and hyperalgesia induced by hind paw injection of carrageenan in rats. Mechanisms underlying contralateral effects of sciatic blockade remain unexplained. Bupivacaine inhibits carrageenan-evoked systemic cytokine production by a mechanism not shared by tetrodotoxin; this action may involve tetrodotoxin-resistant sodium channels or a variety of non-sodium-channel targets.     

不同剂量加巴喷丁对糖尿病神经病理性痛大鼠的镇痛效应

目的 探讨不同剂量加巴喷丁对糖尿病神经病理性痛大鼠的镇痛效应.方法 健康雄性SD大鼠,周龄6周,体重180～200 g,腹腔注射链脲霉素60mg/kg制备糖尿病模型,取模型制备成功的大鼠24只,随机分为4组(n=6):对照组(C组)腹腔注射生理盐水0.6 ml;不同剂量加巴喷丁组(G_(1～3)组)分别腹腔注射加巴喷丁30、60或120 mg/kg,每日2次,每次注射量0.6 ml,连续给药21 d.于加巴喷丁给药前(T_0)、第1次给药后30 min(T_1)、60min(T_2)、120 min(T_3)、180 min(T_4)、240 min(T_5)及给药7 d(T_6)、14 d(T_7)、21 d(T_8)时测定大鼠机械痛阈.结果 各组大鼠机械痛阈基础值比较差异无统计学意义(P>0.05).与C组和G_1组比较,G_2组和G_3组机械痛阈升高(P<0.05);与G_2组比较,G_3组机械痛阈升高(P<0.05).与T_0时比较,G_2组T_(2～8)时机械痛阈升高,G_3组T_(1～8)时机械痛阈升高,两组均于T_2时达峰值(P<0.05).与T_2时比较,G_2组和G_3组T_(1,3～8)时机械痛阈降低(P<0.05).结论 加巴喷丁60和120 mg/kg对糖尿病神经病理性痛大鼠可产生镇痛效应,而长期应用可产生药物耐受现象.     

Sciatic nerve block with bupivacaine-loaded microspheres prevents hyperalgesia in an inflammatory animal model

PURPOSE: The aim of this study was to evaluate the effect of different durations of local anesthetic neural blockade on hyperalgesia after carrageenan infiltration in a rat model. METHODS: Inflammation was obtained by injection of carrageenan in the righ hind paw. Hyperalgesia was determined by measuring the threshold of response to increasing mechanical stimuli on the contralateral and on the ipsilateral paw. The development of edema was measured. After identification of the sciatic nerve by nerve stimulation, blockade was performed either one hour before or after carrageenan infiltration. Animals were randomly assigned into three groups: without sciatic nerve block (control group; n = 20), block with bupivacaine (B) and block with bupivacaine-loaded microspheres (B-Ms) injection before or after carrageenan infiltration (n = 10 for each group). RESULTS: Carrageenan infiltration in the control group induced a severe ipsilateral and contralateral hyperalgesia. After blockade with B (duration = 2 +/- 0.5 hr) hyperalgesia was present and delayed only by the duration of the local anesthetic effect. A longer duration of block achieved with B-Ms (duration greater than five hours), was associated with the absence of development of both ipsilateral and contralateral hyperalgesia. No preemptive effect was recorded. CONCLUSION: B-Ms as a drug delivery system prolongs the duration of neural blockade and avoids hyperalgesia phenomena in this rat model of inflammation.     

Effects of Bupivacaine and Tetrodotoxin on Carrageenan-induced Hind Paw Inflammation in Rats (Part 1): Hyperalgesia, Edema, and Systemic Cytokines

Background: Local anesthetics exert antiinflammatory actions. To elucidate potential mechanisms, the authors examined effects of bupivacaine or tetrodotoxin, administered to rats by ipsilateral or contralateral sciatic blockade or systemically, on carrageenan-induced hind paw hyperalgesia, edema, and stimulated cytokine production in circulating blood cells.

Methods: Twelve groups of rats (n = 9-12) received injections in three sites: (1) right or left hind paw (carrageenan or saline), (2) left sciatic block, and (3) systemically (subcutaneously in the upper back). Sciatic and systemic injections were performed with epinephrine plus bupivacaine, tetrodotoxin, or saline; injections were repeated 6 h later. Fifteen hours later, hyperalgesia and/or sensory and motor block were assessed behaviorally, and paw edema was quantified by magnetic resonance imaging. Stimulated production of tumor necrosis factor [alpha], interleukin 10, and interleukin 1[beta] in whole blood cultures was measured by enzyme-linked immunosorbent assay.

Results: Either ipsilateral or contralateral sciatic blocks using either bupivacaine or tetrodotoxin reduced carrageenan-induced edema and hyperalgesia. Systemic bupivacaine and tetrodotoxin were ineffective in preventing edema and hyperalgesia. Bupivacaine was effective in suppressing systemic tumor necrosis factor [alpha] and interleukin 1[beta] by all three routes, whereas tetrodotoxin was ineffective by all three routes.     

Effect of Prolonged Nerve Block on Inflammatory Hyperalgesia in Rats: Prevention of Late Hyperalgesia

Background: Recent evidence suggests that the duration of the nociceptive block may be an important factor in determining the effect of the block on injury-induced hyperalgesia after block resolution. The authors examined whether a tonicaine nerve block lasting for 12 to 16 h could prevent late inflammatory hyperalgesia.

Methods: Inflammatory hyperalgesia was induced by injection of carrageenan into the rat paw. A threshold of motor response to increasing pressure was determined for the injected paw, contralateral paw, and tail. The development of edema of the paw and an increase in paw temperature also were determined. The block was achieved by simultaneous percutaneous injections of tonicaine (a new long-acting anesthetic agent) or lidocaine at the sciatic nerve (greater trochanter level) and the saphenous nerve (midthigh level).

Results: Carrageenan without nerve block caused a profound primary (injected paw) and secondary (contralateral paw and tail) hyperalgesia that lasted for 3-5 days. Tonicaine nerve block administered before carrageenan completely prevented primary and secondary hyperalgesia. Tonicaine block administered 5 h after carrageenan injection reversed secondary hyperalgesia and prevented the development of late (>or= to 24 h) primary and secondary hyperalgesia. Edema and temperature of the paw were not significantly affected by the nerve block administered before or after carrageenan.     

Analgesic effect of Ga-Al-As diode laser irradiation on hyperalgesia in carrageenin-induced inflammation

This study concerned the effect of Ga-Al-As diode laser irradiation (780 nm, continuous wave, 31.8 J/s/cm², spot size od 0.2 mm, 3 minutes/dose) on hyperalgesia induced in the hind paw of rats by injecting carrageenin. The pressure-pain thresholds of hind paws were measured by the Randall-Selitto test for evaluation of hyperalgesia. Two doses of laser irradiation, given to the inflamed region immediately before and after the injection of carrageenin, partially (～ 50%) inhibited the occurrence of hyperalgesia accompanied with a progression of inflammation. This analgesic effect was equal to that of indomethacin (4 mg/kg, i.o.). In another group, the hyperalgesia was removed almost completely for at least 24 hours by one dose of laser irradiation, which was given 3 hours after the carrageenin injection, whereas the edema was not inhibited. This analgesic effect, however, was partially (～ 50%) antagonized with a dose of 10 mg/kg (i.p.) of naloxone and totally inhibited with 30 mg/kg. These results suggest that low-power laser irradiation on inflamed regions of carrageenin-treated rats has a marked analgesic effect and that certain mechanisms that are not related to endogenous opioids are involved in a part of the mechanisms of the analgesic effects. © 1993 Wiley-Liss, Inc.     

Effects of local anaesthetics on carrageenan-evoked inflammatory nociceptive processing in the rat

We have assessed the effects of intraplantar local anaesthetics (bupivacaine and lignocaine) on carrageenan-induced oedema, mechanical allodynia and spinal c-fos protein expression. Mechanical allodynia was evaluated using the vocalization threshold to paw pressure (VTPP) every 30 min until 60, 180 or 240 min after administration of carrageenan. Peripheral oedema, mechanical allodynia and spinal c-fos protein expression were maximal 180 min after carrageenan. Lignocaine did not influence either oedema or VTPP, but reduced spinal c-fos expression at 60 min after carrageenan without later effects. Bupivacaine induced an increase in VTPP at 30 and 60 min, limitation of oedema at 60 min and a reduction in spinal c-fos expression at 60 and 180 min, but these effects were not present 240 min after carrageenan. Intraplantar infiltration with lignocaine and bupivacaine before carrageenan transiently limited signs of inflammatory pain but did not prevent them.      

Effects of Bupivacaine and Tetrodotoxin on Carrageenan-induced Hind Paw Inflammation in Rats (Part 2): Cytokines and p38 Mitogen-activated Protein Kinases in Dorsal Root Ganglia and Spinal Cord

Background: The authors previously showed that bupivacaine and tetrodotoxin via contralateral or ipsilateral sciatic block, but not systemically, attenuate local edema and hyperalgesia induced by carrageenan hind paw injection in rats. Bupivacaine, by all three routes, suppressed systemic cytokine activation, whereas tetrodotoxin was ineffective by all three routes. In the current study, the authors examined cytokine and p38 mitogen-activated protein kinase (MAPK) activation in lumbar dorsal root ganglia (DRGs) and spinal cord after carrageenan paw injections and sciatic blocks with either bupivacaine or tetrodotoxin.

Methods: Ten groups of rats (n = 3-5) received injections in the following sites: right or left hind paw or right forepaw (carrageenan or saline) and left sciatic block (with epinephrine plus bupivacaine, tetrodotoxin, or saline; repeated 6 h later). Fifteen hours later, tumor necrosis factor [alpha], interleukin 1[beta], p38 MAPK, and phosphorylated p38 MAPK were measured by enzyme-linked immunosorbent assay in DRGs and in the spinal cord.

Results: Carrageenan-induced hind paw inflammation enhanced tumor necrosis factor-[alpha] and interleukin-1[beta] production in bilateral DRGs and spinal cord and enhanced p38 MAPK activation in bilateral DRGs. These pathways were not activated after forepaw injection of carrageenan, suggesting a segmental mechanism. Neither bupivacaine nor tetrodotoxin inhibited cytokine and p38 MAPK activation after carrageenan injection.     

Lack of peripheral analgesia mediated by intraplantar administration of neostigmine in carrageenan-injected rats

BACKGROUND: AND OBJECTIVE: The aim of the study was to test the peripheral analgesic action of neostigmine. Intraplantar administration of neostigmine was studied in carrageenan-injected rats. METHODS: After assessing baseline values (T0) for paw circumference and the paw withdrawal threshold on both hind paws, the right hind paw was injected with 0.2 mL of 1% carrageenan and the left hind paw with 0.2 mL of saline (0.9% NaCl). Two hours later (T1), both hindpaws were tested for inflammation (paw circumference) and for hyperalgesia (paw withdrawal threshold) and subsequently 20 microg of neostigmine was injected in the right hind paw. The paw withdrawal threshold was tested again 10 (T2), 20 (T3) and 60 min (T4) and paw circumference 60 min (T4) after neostigmine injection. RESULTS: Carrageenan injection in the right hindpaw was associated with a decrease in the paw withdrawal threshold reflecting mechanical hyperalgesia (P < 0.001) and an increase in paw circumference reflecting oedema (P < 0.001) in the right hind paw when compared with the left side from T1 to T4. Neostigmine had no effect on paw circumference and the paw withdrawal threshold at measuring points T2, T3 and T4 when compared with T1 in the right hindpaw. CONCLUSION: Our results support the lack of peripheral analgesic effect of neostigmine.     

Plasma concentrations and pharmacokinetics of bupivacaine with and without adrenaline following caudal anaesthesia in infants

BACKGROUND: The aim of this study was to determine whether the use of adrenaline 1/400000 added to 0.25% bupivacaine significantly delays the systemic absorption of the drug from the caudal epidural space in young infants. METHODS: Fifteen infants less than 5 months of age undergoing minor lower abdominal procedures under a standardised general anaesthetic were randomised to receive a caudal block with either 0.25% plain bupivacaine 2.5 mg/kg (n=7) or bupivacaine 0.25% with 1/400000 adrenaline (n=8). Blood samples were drawn at 30, 60, 90, 180, 240 and 360 min according to the infant's weight and analysed for total and free bupivacaine concentrations using a gas chromatography-mass spectrometry (GC-MS) technique. RESULTS: The total C(MAX) and T(MAX) were comparable in both groups. The total bupivacaine concentration at t=360 min was significantly higher in the "adrenaline" group compared to the "plain" group, i.e. a median (range) 742 ng/ml (372-1423 ng/ml) vs. 400.5 ng/ml (114-446 ng/ml), P=0.0080. The median "apparent" terminal half-life (t1/2) was significantly longer in the "adrenaline" group (363 min; range 238-537 min) compared to the "plain" group (n=6) (165 min; range 104-264 min), P=0.0087. The free bupivacaine concentrations (n=3 in both groups) ranged between 13 ng/ml and 52 ng/ml, corresponding to a percentage of free bupivacaine between 1.3% and 6.7%. CONCLUSION: The addition of 1/400.000 adrenaline prolongs the systemic absorption of caudally administered bupivacaine in infants less than 5 months of age.     

Effects of bupivacaine and tetrodotoxin on carrageenan-induced hind paw inflammation in rats (Part 2): cytokines and p38 mitogen-activated protein kinases in dorsal root ganglia and spinal cord

BACKGROUND: The authors previously showed that bupivacaine and tetrodotoxin via contralateral or ipsilateral sciatic block, but not systemically, attenuate local edema and hyperalgesia induced by carrageenan hind paw injection in rats. Bupivacaine, by all three routes, suppressed systemic cytokine activation, whereas tetrodotoxin was ineffective by all three routes. In the current study, the authors examined cytokine and p38 mitogen-activated protein kinase (MAPK) activation in lumbar dorsal root ganglia (DRGs) and spinal cord after carrageenan paw injections and sciatic blocks with either bupivacaine or tetrodotoxin. METHODS: Ten groups of rats (n = 3-5) received injections in the following sites: right or left hind paw or right forepaw (carrageenan or saline) and left sciatic block (with epinephrine plus bupivacaine, tetrodotoxin, or saline; repeated 6 h later). Fifteen hours later, tumor necrosis factor alpha, interleukin 1beta, p38 MAPK, and phosphorylated p38 MAPK were measured by enzyme-linked immunosorbent assay in DRGs and in the spinal cord. RESULTS: Carrageenan-induced hind paw inflammation enhanced tumor necrosis factor-alpha and interleukin-1beta production in bilateral DRGs and spinal cord and enhanced p38 MAPK activation in bilateral DRGs. These pathways were not activated after forepaw injection of carrageenan, suggesting a segmental mechanism. Neither bupivacaine nor tetrodotoxin inhibited cytokine and p38 MAPK activation after carrageenan injection. CONCLUSION: Ipsilateral or contralateral sciatic blockade using either bupivacaine or tetrodotoxin does not inhibit carrageenan-induced activation of cytokines and p-38 MAPK in spinal cord and DRGs. Possible explanations may include incomplete degrees of conduction blockade or afferent signaling via saphenous nerves.     

NF-κB信号通路在鞘内注射血小板活化因子诱发大鼠痛敏中的作用

目的 评价NF-κB信号通路在鞘内注射血小板活化因子(PAF)诱发大鼠痛敏中的作用.方法 鞘内置管成功的雄性SD大鼠64只,体重200～250 g,随机分为6组:人工脑脊液(ACSF)对照组(AC组,n=16)鞘内注射ACSF 10μl;PAF诱发大鼠痛敏组(PAF组,n=16)鞘内注射PAF 10μg(溶于10μl ACSF);二甲基亚砜(DMSO)对照组(DC组,n=8)和低、中和高剂量SC-514组(S1-3组,n=8)分别于鞘内注射PAF前2 h腹腔注射0.1%DMSO溶液2 ml、SC-514(溶于2 ml 0.1%DMSO溶液)10、50、100 mg/kg.分别于鞘内给药前、给药后5、15、30、45和60 min时测定机械痛阈和热痛阈,随后每间隔30 min测定1次,连续4 h,ELISA法检测脊髓TNF-α和IL-lβ的表达.结果 鞘内注射PAF可诱发机械痛敏和热痛敏,上调大鼠脊髓TNF-α和IL-1β的表达;Iκβ激酶-β抑制剂SC-514可剂量依赖性地减轻PAF诱发的痛敏,抑制脊髓TNF-α和IL-1β的表达上调.结论 NF-κB信号通路参与了鞘内注射PAF诱发大鼠痛敏的过程.     

Plasma concentrations of bupivacaine after brachial plexus administration of liposome-associated and plain solutions to rabbits

Bupivacaine has been associated to multilamellar liposomes with the aim of altering circulating plasma concentrations after injection into the rabbit brachial plexus. Plasma concentrations of bupivacaine have been compared after administration of free drug (BP) or bupivacaine associated to multilamellar liposomes (BP-MLV) made of phosphatidylcholine and cholesterol (molar ratio 4:3). Under light general anaesthesia, one group of six rabbits received an axillary injection of 2.5 mg BP (1 ml, 0.25%), and a second received the same dose of BP-MLV. In both groups³H bupivacaine was used as a marker. The brachial plexus was located using a nerve stimulator. Injection of the anaesthetic solutions invariably prevented the motor response of the paw. The arterial plasma concentrations of bupivacaine were determined after 5 to 240 min and after 24 hr by beta counting. In the MLV population, additional measurements were performed after 48 and 72 hr. The two plasma curves showed a plateau (0.2 μg · ml^?1) which was reached after five minutes in the BP group and after 90 min using BP-MLV In the BP-MLV group, the plasma concentrations of bupivacaine were lower during the first ten minutes (P < 0.05), and higher after 24 hr (P < 0.05). Radioactivity decreased between 4 and 24 hr in the BP group and between one and two days in the BP-MLV population. It is concluded that elevated plasma drug concentrations were maintained for longer with BP-MLV than with BP This could prolong the action of the local anaesthetic through a slow release.     

Fentanyl Enhancement of Carrageenan-induced Long-lasting Hyperalgesia in Rats: Prevention by the N-methyl-d-aspartate Receptor Antagonist Ketamine

Background: Tissue damage may produce hyperalgesia, allodynia, and persistent pain. The authors recently reported that fentanyl elicits analgesia but also activates N-methyl-d-aspartate-dependent pain facilitatory processes opposing analgesia. In nonsuffering rats, this leads to a long-lasting enhancement in pain sensitivity. The current study assessed whether fentanyl could amplify carrageenan-induced hyperalgesia.

Methods: First, rats were injected once with carrageenan in a hind paw, with fentanyl (60 or 100 [mu]g/kg each given four times at 15-min intervals [4 x 60 or 4 x100]) or saline. Second, rats were injected with carrageenan twice without fentanyl (7-day interval), with the second injection either in the previously injected paw or in the other paw. Third, rats were injected twice with carrageenan in the same hind paw: the first ketamine injection was given (10 mg/kg each given three times at 5-h intervals) with or without fentanyl (4 x 60 [mu]g/kg), and second injection was given without ketamine or fentanyl. The consequences of treatments on long-term hyperalgesia were examined by the paw-pressure vocalization test.

Results: The long-lasting hyperalgesia induced by the first carrageenan injection was dose-dependently enhanced in both duration and magnitude in 4 x 60 or 4 x 100 [mu]g/kg fentanyl-treated rats: 5 or 10 days, respectively, as compared with 2 days in saline-treated rats. Hyperalgesia observed in the hind paw contralateral to the first carrageenan injection was enhanced in fentanyl-treated rats. The second carrageenan injection, performed in any hind paw, induced an exaggerated hyperalgesia, especially in fentanyl-treated rats. Pretreatment with ketamine totally prevented the carrageenan- and fentanyl-induced enhancement of the long-lasting hyperalgesia.     

Does speed of intrathecal injection affect the distribution of 0.5% hyperbaric bupivacaine?

We have evaluated the influence of speed of intrathecal injection on lateral distribution of 0.5% hyperbaric bupivacaine. We studied 60 patients undergoing lower limb surgery who were placed in the lateral position with the operative side in the dependent position. After dural puncture (25-gauge Whitacre spinal needle), the needle aperture was turned towards the dependent side and 0.5% hyperbaric bupivacaine 8 mg was injected randomly at a rate of 0.02 ml s-1 (group slow, n = 30) or 0.25 ml s-1 (group fast, n = 30). Lateral position was maintained for 15 min while a blinded observer recorded loss of pinprick sensation and degree of motor block on both surgical and non-surgical sides. There were no differences between the groups. Forty-five minutes after patients were turned to the supine position, spinal anaesthesia was unilateral in 17 patients in group slow (56%) and in 13 patients in group fast (43%). We conclude that using extremely low speeds for intrathecal injection were not clinically advantageous in obtaining unilateral spinal anaesthesia.      

A comparison of 0.1% and 0.2% ropivacaine and bupivacaine combined with morphine for postoperative patient-controlled epidural analgesia after major abdominal surgery

Ropivacaine (ROPI), which is less toxic and produces less motor block than bupivacaine (BUPI), seems attractive for epidural analgesia. Few data are available concerning dose requirements of epidural ROPI when combined with morphine. In this study, we compared the dose requirements and side effects of ROPI and BUPI combined with small-dose morphine after major abdominal surgery. Postoperatively, 60 patients were randomly allocated (double-blinded manner) to four groups: patient-controlled epidural analgesia with the same settings using 0.1% or 0.2% solution of ROPI or BUPI combined with an epidural infusion of 0.1 mg/h of morphine. Pain scores, side effects, motor block, and local anesthetic consumption were measured for 60 h. Pain scores and the incidence of side effects did not differ among the groups. Consumption of ROPI and BUPI were similar in both 0.1% groups. Doubling the concentration significantly reduced the consumption (milliliters) of BUPI (P < 0.05) but not of ROPI. Consequently, using ROPI 0.2% significantly increased the dose administered as compared with ROPI 0.1% (ROPI 0.1% = 314 +/- 151 mg and ROPI 0.2% = 573 +/- 304 mg at Hour 48; P < 0.05). Patient-controlled epidural analgesia with the 0.1% or 0.2% solution of ROPI or BUPI combined with epidural morphine resulted in comparable analgesia. As compared with ROPI 0.1%, the use of ROPI 0.2% increased consumption of local anesthetic without improving analgesia. IMPLICATIONS: Small-dose (0.1%) ropivacaine and bupivacaine have similar potency and result in comparable analgesia and incidence of side effects.     

Tremor and epidural anesthesia

To evaluate the influence of temperature of the injected anesthetic solution on the development of tremor during epidural anesthesia, 66 patients divided in three homogeneous groups were evaluated: group I (n = 22; bupivacaine 4 degrees C), group II (n = 24; bupivacaine 20 degrees C), and group III (n = 24; bupivacaine 37 degrees C). The incidence of tremor was 20% (4 patients) in group I, 9% (2 patients) in group II and 12.5% (3 patients) in group III. No significant differences were found between the groups. The overall incidence was 13.6%. The epidural injection of 5 ml of saline at 37 degrees C achieved the attenuation and/or disappearance of tremor in three (3/4) group I patients (4 degrees C) and in one (1/3) group III patient (37 degrees C), whereas it was ineffective in one patient from group I and one from group III. In the two patients from group II (20 degrees C) and in one from group III (37 degrees C), tremor was self-limited. We conclude that the incidence of tremor during epidural anesthesia is not correlated with the temperature of anesthetic solutions, and that the epidural injection of saline at 37 degrees C may give some therapeutic benefit.     

The pre-emptive analgesic effect of intra-articular bupivacaine in arthroscopic knee surgery

BACKGROUND: The purpose of this study was to determine whether intra-articular injection of bupivacaine prior to surgery provided better pain control after arthroscopic meniscectomy as compared with post-operative administration of bupivacaine. METHODS: Forty patients of American Society of Anesthesiologists (ASA) class I or II undergoing arthroscopic meniscectomy were assigned in a randomized, double-blinded manner into two groups: Group I received 20 ml of 2.5 mg/ml bupivacaine without epinephrine 30 min before skin incision and 20 ml of saline immediately after skin closure. Group II received identical injections in reverse order. All patients received total intravenous anesthesia. Post-operative pain scores were evaluated at 1, 2, 4, 6, 8, 12 and 24 h at rest and movement of the knee, using a 10-cm visual analog scale (VAS). The time to first analgesic use and 24-h analgesic consumption were recorded. RESULTS: Pain scores were lower in Group I compared with Group II at 1, 2, 4 and 6 h at rest and on movement (P < 0.05). The time to first analgesic use was longer in Group I, but there was no statistically significant difference in 24-h analgesic consumption. CONCLUSION: Intra-articular bupivacaine administered before surgery provided a statistically significant reduction in post-operative pain scores compared with post-operative bupivacaine administration.     

中枢敏化和外周敏化在瑞芬太尼诱发炎性痛大鼠痛觉过敏中的作用

目的 探讨中枢敏化和和外周敏化在瑞芬太尼诱发炎性痛大鼠痛觉过敏中的作用.方法 雄性SD大鼠21只,体重200～300 g,采用随机数字表法,将其随机分为3组(n=7):生理盐水对照组(C组)、低剂量瑞芬太尼组(R1组)和高剂量瑞芬太尼组(R2组),3组均采用左侧跖底皮下注射1%角叉菜胶100 μl的方法制备大鼠炎性痛模型.R1组和R2组于造模前5 min至造模后25 min分别静脉输注瑞芬太尼10、30 μg·kg-1·min-1,C组给予等容量生理盐水.分别于造模前、造模后1 h、3 h、1～7 d时测定双侧机械缩足阈值(PWT);分别于造模前、造模后2 h、4 h、1～7 d时测定双侧热刺激缩足潜伏期(PWL);分别于造模前、造模后1 h,4 h、1～7 d时测定左侧后爪跖底的厚度.结果 与C组比较,R1组和R2组在造模后1 d时双侧PWT降低(P＜0.05);与R1组比较,R2组在造模后2、4～7 d时右侧PWT降低(P＜0.05);3组间双侧PWL和左侧后爪跖底厚度比较差异无统计学意义(P＞0.05).结论 中枢敏化参与了瑞芬太尼诱发炎性痛大鼠痛觉过敏的发生和维持,而外周敏化未参与.

Abstract：

Objective To investigate the role of central and peripheral sensitization in remifentanil-induced hyperalgesia in a rat model of inflammatory pain. Methods Twenty-one male SD rats weighing 200-300 g were used in this study. Inflammatory pain was induced by intraplantar injection of 1 % carrageenan 100 fd in the left hindpaw in all animals. The animals were then randomly divided into 3 groups ( n = 7 each): control group (group C) and two remifentanil groups (group R1 , R2) . In R1 and R2 groups remifentanil was infused iv at a rate of 10 and 30 μg-kg-1·min-2 respectively starting from 5 min before till 25 min after carrageenan injection, while in group C normal saline was infused iv instead of remifentanil. Bilateral paw withdrawal threshold to mechanical stimulation with von Frey filament (PWT) was measured before (baseline) and at 1 h, 3 h and 1-7 d after carrageenan injection. Bilateral paw withdrawal latency to noxious thermal stimuli (PWL) was measured before and at 2 h, 4 h and 1-7 d after carrageenan injection. The thickness of the plantar surface of left hindpaw was measured before and at 1 h, 4 h and 1-7 d after carrageenan injection. Results Bilateral PWT was significantly lower at day 1 after carrageenan injection in R, and R2 groups than in group C. The right PWT was significantly lower at 2 d and 4-7 d after carrageenan injection in group R2 than in group R, . There was no significant difference in PWL and thickness of the plantar surface of left hindpaw among the 3 groups. Conclusion Central sensitization is involved in developing and maintaining the remifentanil-induced hyperalgesia in a rat model of inflammatory pain, while peripheral sensitization is not.     

氯胺酮预防瑞芬太尼痛觉过敏的实验研究

目的 观察预先皮下注射氯胺酮对瑞芬太尼诱发切口痛模型大鼠痛觉过敏的影响.方法 雄性SD大鼠60只,将大鼠随机分为5组:对照组(C组)、切口痛组(Ⅰ组)、氯胺酮(K组)、瑞芬太尼组(R组)、氯胺酮+瑞芬太尼组(K+R组).Ⅰ组,K组,R组和K+R组行右后足跖肌切口;K组和K+R组术前单次皮下注射氯胺酮0.1 ml(10mg/kg);R组和K+R组切皮开始同时皮下泵注瑞芬太尼0.4 nl(0.04 mg/kg),泵注时间为30 min,所有动物手术和接受微量泵皮下输注均在吸入七氟醚麻醉下进行.于术前24 h、术后2、6、24、48 h检测痛行为学指标,包括机械缩足阈值(paw withdrawal mechanical threshold,PWMT)和热缩足反射潜伏期(paw withdrawal thermal latency,PWTL).结果 与C组和基础值比较,Ⅰ组术后各时间点PWMT和PWTL均降低(P＜0.05);与Ⅰ组相比,R组术后2 h PWMT(6.48±1.23)g和PWTL(11.13±1.95)s即开始降低,此水平持续至术后48h(P<0.05);K+R组术后各时间点PWMT(9.36±1.76,9.41±1.50,10.18±1.42,10.15±1.48)g和PWTL(15.66±2.42,16.24±2.55,15.13±3.07,15.66±2.44)s均高于R组(P＜0.05).结论 术前预先皮下注射氯胺酮可有效预防瑞芬太尼诱发的切口痛模型大鼠痛觉过敏.