Effect of systemic adenosine on pain and secondary hyperalgesia associated with the heat/capsaicin sensitization model in healthy volunteers

BACKGROUND AND OBJECTIVES: Adenosine is an endogenous compound that may have analgesic effects. Results from clinical trials are not consistent, however, and there is a need for large-scale, randomized, placebo-controlled studies to clarify the role of adenosine in the treatment of pain states, including acute nociceptive pain and pain involving central sensitization. METHODS: The analgesic and antihyperalgesic effect of systemic adenosine on the heat/capsaicin sensitization model of experimental pain was investigated in 25 healthy human volunteers. Sensitization was produced by heating the skin to 45 degrees C for 5 minutes, followed by a 30-minute application of 0.075% capsaicin cream, and maintained by periodically reheating the sensitized skin to 40 degrees C for 5 minutes at 40-minute intervals. Subjects received intravenous adenosine 60 microg/kg/min or saline for 85 minutes. Areas of secondary hyperalgesia to von Frey hair and brush stimulation, heat-pain detection thresholds (HPDTs) in normal and sensitized skin, and painfulness of stimulation with 45 degrees C for 1 minute (LTS) in normal skin were quantified before, during, and after study drug infusion. RESULTS: Systemic adenosine had no effect on the area of secondary hyperalgesia to von Frey hair or brush stimulation, HPDT in normal or sensitized skin, or painfulness of LTS in normal skin. CONCLUSION: We conclude that adenosine has no effect on acute nociceptive pain induced by heat stimulation or on secondary hyperalgesia induced by heat/capsaicin sensitization in healthy volunteers.     

Effect of intravenous magnesium on pain and secondary hyperalgesia associated with the heat/capsaicin sensitization model in healthy volunteers

We investigated the effects of i.v. magnesium on secondary hyperalgesiafollowing heat/capsaicin stimulation in human volunteers. Twenty-fivevolunteers were included in this double blind, randomized, crossoverstudy. Sensitization was induced in the volunteers, who werethen subjected to either i.v. saline or magnesium sulphate.No analgesic or antihyperalgesic effect could be demonstratedin sensitized skin during infusion of magnesium. In contrast,painfulness of thermal stimulation was increased in normal skin.These results suggest that i.v. magnesium has no important analgesiceffects in clinically relevant doses. Br J Anaesth 2001; 86: 871–3     

Effect of remifentanil on pain and secondary hyperalgesia associated with the heat--capsaicin sensitization model in healthy volunteers

BACKGROUND: The heat--capsaicin sensitization model was developed as a noninvasive and noninjurious human experimental pain model. The sequential application of moderate intensity thermal and topical chemical stimuli produces stable and long-lasting areas of cutaneous secondary hyperalgesia. The aim of the present study was to validate the heat--capsaicin sensitization model as a tool for testing analgesic drug efficacy. Responsivity of model-associated measures was tested with remifentanil, a potent and ultrashort acting mu-opioid agonist. METHODS: Sensitization was induced by heating forearm skin with a thermode at 45 degrees C for 5 min, immediately followed by application of 0.075% capsaicin cream for 30 min. Sensitization was rekindled four times at 40-min intervals with the thermode at 40 degrees C for 5 min. After each rekindling, areas of secondary hyperalgesia were measured, and the painfulness of thermal stimulation in normal skin with 45 degrees C for 1 min (long thermal stimulation [LTS]) was rated. Before and during the second rekindling, remifentanil 0.10 microg x kg(-1) x min(-1) or saline-placebo was infused for 35 min. RESULTS: Infusion of remifentanil reduced the areas of secondary hyperalgesia to 29--30% of baseline size compared with 75--83% during placebo. Similarly, remifentanil reduced the painfulness of LTS to 29% of baseline severity compared with 84% during placebo. Areas of secondary hyperalgesia and LTS painfulness returned to baseline levels by the time of the third rekindling, demonstrating rapid disappearance of remifentanil analgesia and possibly transient spontaneous opioid withdrawal hyperalgesia. CONCLUSION: Using the heat-capsaicin sensitization model, opioid analgesia and suppression of secondary hyperalgesia was reliably demonstrated without skin injury.     

The effects of remifentanil and gabapentin on hyperalgesia in a new extended inflammatory skin pain model in healthy volunteers

We tested the responsiveness of measures of hyperalgesia in a model of UVB-induced inflammatory hyperalgesia with remifentanil, gabapentin, and the combination of both drugs in a double-blinded, active placebo-controlled, 4-way-crossover design in 16 volunteers. A circular skin area was irradiated with UVB-light 20 h before the application of gabapentin (600 mg) and 2 h later remifentanil (0.08 microg.kg(-1).min(-1), 40 min). In the sunburn spots we observed stable decreases of the heat pain perception thresholds (HPPT, mean difference, 4.45 degrees C; 95% confidence interval [CI], 3.32 degrees -5.59 degrees ) and heat pain tolerance thresholds (HPTT; mean difference, 5.43 degrees C; 95% CI, 4.50 degrees -6.35 degrees ) compared with normal skin. Further, large areas of mechanical hyperalgesia to pinprick adjacent to the erythema spots developed in all subjects. Overall remifentanil increased the HPPT (mean increase, 2.47 degrees C; 95% CI, 1.86 degrees -3.09 degrees, P < 0.001) and HPTT (mean increase, 3.18 degrees C; 95% CI, 2.65 degrees -3.71 degrees, P < 0.001) and reduced the area of secondary hyperalgesia by 59% (mean decrease, 5326 mm(2); 95% CI, 4233-6419 mm(2), P < 0.001) compared with placebo. In the sunburn remifentanil markedly increased the HPTT by 86% compared with normal skin (additional increase, 2.57 degrees C; 95% CI, 1.71 degrees -3.43 degrees). This different effect was not seen in the HPPT. With the exception of a small increase of HPTT in the sunburn (P = 0.02) gabapentin had no noticeable effect on either hyperalgesia. In conclusion, opioid analgesia was reliably demonstrated in this new extended pain model. IMPLICATIONS: Opioid analgesia was reliably demonstrated in a new inflammatory model of primary and secondary hyperalgesia. Gabapentin showed no antihyperalgesic and no opioid-enhancing effect in this model.     

Dose-dependent effects of smoked cannabis on capsaicin-induced pain and hyperalgesia in healthy volunteers

BACKGROUND: Although the preclinical literature suggests that cannabinoids produce antinociception and antihyperalgesic effects, efficacy in the human pain state remains unclear. Using a human experimental pain model, the authors hypothesized that inhaled cannabis would reduce the pain and hyperalgesia induced by intradermal capsaicin. METHODS: In a randomized, double-blinded, placebo-controlled, crossover trial in 15 healthy volunteers, the authors evaluated concentration-response effects of low-, medium-, and high-dose smoked cannabis (respectively 2%, 4%, and 8% 9-delta-tetrahydrocannabinol by weight) on pain and cutaneous hyperalgesia induced by intradermal capsaicin. Capsaicin was injected into opposite forearms 5 and 45 min after drug exposure, and pain, hyperalgesia, tetrahydrocannabinol plasma levels, and side effects were assessed. RESULTS: Five minutes after cannabis exposure, there was no effect on capsaicin-induced pain at any dose. By 45 min after cannabis exposure, however, there was a significant decrease in capsaicin-induced pain with the medium dose and a significant increase in capsaicin-induced pain with the high dose. There was no effect seen with the low dose, nor was there an effect on the area of hyperalgesia at any dose. Significant negative correlations between pain perception and plasma delta-9-tetrahydrocannabinol levels were found after adjusting for the overall dose effects. There was no significant difference in performance on the neuropsychological tests. CONCLUSIONS: This study suggests that there is a window of modest analgesia for smoked cannabis, with lower doses decreasing pain and higher doses increasing pain.     

The effect of remifentanil on the heat pain threshold in volunteers

Remifentanil offers a wide range of clinical uses and has been successfully combined with general anesthetics. However, there are few human experimental studies demonstrating the analgesic property of remifentanil. It was our aim to determine the analgesic effect of remifentanil with regard to dose-dependent increments in a human model of heat pain threshold assessment. Twenty healthy volunteers were randomized in a double-blinded cross-over design to receive an infusion of remifentanil or saline. The stepped infusion was increased every 5 min by 0.01 microg. kg(-1). min(-1) up to 0.17 microg. kg(-1). min(-1)and terminated in case of defined safety limits. Thermal sensory testing of the heat pain threshold was performed every 5 min at the left forearm. The dose-response relationship and the effective dose for at least 50% of the subjects (ED(50)) were determined. Remifentanil led to a clear dose-dependent increase of the heat pain threshold differing significantly from placebo (P < 0.0007). The ED(50) of remifentanil equals 0.05 microg. kg(-1). min(-1) (first quartile 0.025 microg. kg(-1). min(-1) and third quartile 0.06 microg. kg(-1). min(-1)) in this experimental setting. In conclusion, an opioid-mediated analgesic effect of remifentanil was determined in a human heat pain threshold model. The dose of 0.05 microg. kg(-1). min(-1) is an effective and safe increment in healthy volunteers.     

The effect of intravenous infusion of adenosine on electrically evoked hyperalgesia in a healthy volunteer model of central sensitization

Human pain models invoking central sensitization, one of the key mechanisms of chronic pain, may be useful for characterizing new analgesics. A new model of electrical hyperalgesia can detect the efficacy of several analgesic mechanisms. Because IV adenosine can alleviate neuropathic pain, we investigated its effect on experimental sensitization. This was a double-blinded, randomized, two-period crossover study in 20 healthy volunteers. Current pulses (0.5 ms; 1 Hz) were applied intracutaneously to achieve pain rating of approximately 5 on a 0-10 numeric rating scale. Pain, areas of pinprick hyperalgesia, and tactile allodynia were assessed during the 2.5-h stimulation period. Adenosine (50 microg. kg(-1). min(-1)) and placebo were infused IV over 60 min. Additional testing was performed 24 h after each treatment. Adenosine reduced the area of pinprick hyperalgesia during the infusion compared with placebo; there was no significant effect on tactile allodynia or pain rating. The effect on hyperalgesia developed over 15 min and was significant (P < or = 0.05) for the rest of the infusion period. There was no difference between treatments at 24 h. Thus, in accordance with reports on neuropathic pain, adenosine reduced central sensitization in the human model of electrical hyperalgesia. However, adenosine did not have the long-term effects seen in patients. The model can investigate mechanisms of drugs for the treatment of chronic pain.     

Lack of secondary hyperalgesia and central sensitization in an acute sheep model

BACKGROUND AND OBJECTIVES: We aimed to determine the following in an experimental acute pain model in sheep: (1) whether multimodal analgesia with intravenous fentanyl and ketorolac was more effective than fentanyl alone; (2) whether secondary hyperalgesia (central sensitization) occurred in adjacent (foreleg) dermatomes after thoracic surgery; (3) whether ketorolac used preemptively influenced the development of secondary hyperalgesia after surgery. METHODS: Changes in primary nociception were measured by increases to tolerated pressure, applied to the foreleg by a blunt pin, before foreleg withdrawal occurred. Changes to breath-to-breath interval and estimated end-tidal CO2 were used as indices of respiratory effects. Study 1 (n = 6) compared the paired responses to acute nociception after ketorolac (90 mg) or saline (control) pretreatment, followed by fentanyl (graded, 0 mg to 1.5 mg). Study 2 (n = 6) used a cross-over of ketorolac (90 mg) or saline (control) 24 hours and 1 hour, respectively, before a standardized thoracotomy incision, followed by antinociceptive testing with ketorolac (90 mg) and fentanyl (0.6 mg) daily over 4 days. RESULTS: In study 1, fentanyl produced naloxone-antagonizable antinociception and respiratory depression. Ketorolac did not affect fentanyl antinociception, except for prolonging antinociception at the highest dose; it did not affect the respiratory effects. In study 2, preemptive ketorolac had no effect on the postoperative antinociceptive or respiratory effects of fentanyl. The pharmacokinetics of fentanyl were unaltered by ketorolac. CONCLUSIONS: The results obtained in this acute pain model found no significant evidence of a fentanyl-ketorolac interaction, of central sensitization as shown by secondary hyperalgesia, or of a preemptive analgesic effect.     

Adenosine increases the cutaneous heat pain threshold in healthy volunteers

Adenosine is an endogenously produced substance which in animal experiments exerts anti-nociceptive effects. In humans, algcsic effects have been presented following exogenous adenosine administration. A recent study on anaesthetized patients, however, suggested an anti-nociceptive effect during i.v. adenosine. We have studied the pain-reducing effect in healthy volunteers using adenosine 50–80 μg · kg^-1 · min^-1 (n = 10), morphine 0.1 mg · kg^-1 (n = 5), adenosine 50 μg · kg ^-1 · min^-1 + morphine 0.1 mg · kg^-1 (n=6), and ketamine 0.1 mg · kg^-1 (n=5); all drugs given i.v., single-blind. Quantitative sensory tests (QST) revealed a significantly increased cutaneous heat pain threshold following adenosine. No effect was seen following ketamine or morphine. Suprathreshold heat pain perception was unchanged in all subjects. Furthermore, warm and cold perception thresholds were not influenced significantly by any drug. Adenosine, morphine and kctamine produced well-known side-effects but of a mild intensity not necessitating any treatment.
The present results show that i.v. adenosine can provide a modest but selective increase of cutaneous heat pain thresholds, suggesting a pain-reducing capacity of adenosine in humans.     

Hypnosis increases heat detection and heat pain thresholds in healthy volunteers.

BACKGROUND AND OBJECTIVES: Hypnosis has been reported to induce analgesia and to facilitate anesthesia. To date, hypnotic-induced analgesia has had little explanation and it has even been questioned. The current study was thus designed to investigate the effect of hypnotic suggestion on thermal-detection thresholds, heat pain, and heat-pain tolerance thresholds. METHODS: In 15 healthy volunteers, enrolled in a randomized cross-over study, thermal thresholds were investigated in 2 sequences of measurements, under waking and hypnotic states, using a thermal stimulator. RESULTS: Heat detection and heat-pain thresholds were increased under hypnosis (from 34.3 +/-.9 degrees C to 36.0 +/- 2.9 degrees C and 45.0 +/- 3.7 degrees C to 46.7 +/- 2.7 degrees C, respectively, P <.05), whereas heat-pain tolerance and cold-detection thresholds were not statistically changed. CONCLUSION: These results indicate that hypnosis may partly impair the detection of A delta and C fibers stimulation, potentially explaining its analgesic effect.     

Primary and secondary hyperalgesia in a rat model for human postoperative pain

BACKGROUND: Previously, the authors developed and characterized a rat model for postoperative pain to learn more about pain produced by incisions. In this study, the responses to heat and mechanical stimuli were evaluated directly on or adjacent to the incision and at varying distances from the incision. METHODS: Rats were anesthetized with halothane and incisions were made at different locations in the plantar aspect of the foot. The response frequency to a blunt mechanical stimulus, the withdrawal threshold to von Frey filaments (15-522 mN), and the withdrawal latency to radiant heat were measured. Rats were tested before surgery, 2 h later, and then daily through postoperative day 9. RESULTS: After plantar incision, persistent hyperalgesia was observed immediately adjacent to or directly on the incision to punctate and blunt mechanical stimuli, respectively. The withdrawal threshold to punctate stimuli applied 1 cm from the incision was decreased through postoperative day 1. In a transitional area, between the distant and adjacent sites, the withdrawal threshold was intermediate and the duration of hyperalgesia was transient. Heat hyperalgesia was persistent but present when the stimulus was applied to the site of injury but not to a distant site. CONCLUSION: Robust primary hyperalgesia to punctate and blunt mechanical stimuli was present. Hyperalgesia distant to the wound, or secondary hyperalgesia, occurred in response to punctate mechanical stimuli, was short-lived, and required greater forces. These results suggest that the most persistent pain behaviors in this model are largely primary hyperalgesia.     

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.     

Differential effects of systemically administered ketamine and lidocaine on dynamic and static hyperalgesia induced by intradermal capsaicin in humans

We have examined the effect of systemic administration of ketamine and lidocaine on brush-evoked (dynamic) pain and punctate-evoked (static) hyperalgesia induced by capsaicin. In a randomized, double-blind, placebo-controlled, crossover study, we studied 12 volunteers in three experiments. Capsaicin 100 micrograms was injected intradermally on the volar forearm followed by an i.v. infusion of ketamine (bolus 0.1 mg kg- 1 over 10 min followed by infusion of 7 micrograms kg-1 min-1), lidocaine 5 mg kg-1 or saline for 50 min. Infusion started 15 min after injection of capsaicin. The following were measured: spontaneous pain, pain evoked by punctate and brush stimuli (VAS), and areas of brush- evoked and punctate-evoked hyperalgesia. Ketamine reduced both the area of brush-evoked and punctate-evoked hyperalgesia significantly and it tended to reduce brush-evoked pain. Lidocaine reduced the area of punctate-evoked hyperalgesia significantly. It tended to reduce VAS scores of spontaneous pain but had no effect on evoked pain. The differential effects of ketamine and lidocaine on static and dynamic hyperalgesia suggest that the two types of hyperalgesia are mediated by separate mechanisms and have a distinct pharmacology.      

The sunburn pain model: the stability of primary and secondary hyperalgesia over 10 hours in a crossover setting

It was our aim to study the within-day stability and between-day repeatability of ultraviolet B (UVB) light-induced primary and secondary hyperalgesia over 10 h. Twenty hours after UVB irradiation of a skin spot (r = 2.5 cm) on the upper leg of 8 healthy volunteers the areas of secondary hyperalgesia to pinprick and pain tolerance thresholds to heat (HPTT) and electrical stimuli (5 and 250 Hz, electrical pain tolerance thresholds [EPTT]) were assessed. Measurements were repeated for 10 h at 2-h intervals and in 2 different sessions. Large areas of secondary hyperalgesia to pin prick were observed (5995 mm(2); SD, 1645). Primary hyperalgesia was evidenced by significant decreases of HPTT (mean difference, 6.5 degrees C; 95% confidence interval, 6.1-6.8; P < 0.001) and EPTT at 250 Hz (mean difference, 0.45 mA; 95% confidence interval, 0.13-0.78; P < 0.05) compared to normal skin. There was no trend within one session of either primary (P = 0.14 for HPTT) or secondary hyperalgesia (P = 0.95) and no difference between the two sessions (primary hyperalgesia, P = 0.28; secondary hyperalgesia, P = 0.07). The sunburn pain model provides a long time course of stable hyperalgesia with a high within-day stability and between-day repeatability for primary and secondary hyperalgesia. IMPLICATIONS: The sunburn pain model provides a long time course of stable hyperalgesia with a high within-day stability and between-day repeatability for primary and secondary hyperalgesia.     

Amiodarone decreases heat, cold, and mechanical hyperalgesia in a rat model of neuropathic pain

Lidocaine is effective in controlling ventricular dysrhythmia and neuropathic pain. Amiodarone, like lidocaine, has sodium channel blocking properties. In the present study we explore whether amiodarone has a similar effect as lidocaine on the heat, cold, and mechanical hyperalgesia seen in the rat model of neuropathic pain. Ten male Sprague-Dawley rats were anesthetized. Four loose ligatures were placed on the sciatic nerve of the right hindpaw. A sham operation was performed on the contralateral hindpaw (control). Heat hyperalgesia was determined by comparing each paw withdrawal latency to heat stimulation (radiant heat source, 50 degrees C). Cold hyperalgesia was assessed with acetone application. Mechanical hyperalgesia was determined by comparing the mechanical threshold in the ligated and control hind paws using calibrated von Frey filaments. Amiodarone was intraperitoneally administered at doses of 1, 5, 10, 20, 50, and 100 mg/kg after the development of hyperalgesia. The animals were tested for hyperalgesia before and 1, 3, and 24 h after the administration of a single dose of amiodarone. Intrathecal catheters were implanted in 5 new rats, and amiodarone 5 mg/kg was injected. Testing for heat, mechanical, and cold hyperalgesia was performed similarly in the intrathecal amiodarone administration group. Amiodarone produces statistically significant decreases of heat, cold, and mechanical hyperalgesia after intraperitoneal administration. Results are statistically significant at 10 mg/kg (heat hyperalgesia), 20 mg/kg (mechanical hyperalgesia), and 100 mg/kg (cold hyperalgesia) intraperitoneally. Hyperalgesia returns 24 h after a dose. The intrathecal administration of amiodarone produces a nonstatistically significant reduction of hyperalgesia. Amiodarone seems to have a similar effect as lidocaine on the hyperalgesia seen in the rat model of neuropathic pain. As the half-life of amiodarone is significantly longer that that of lidocaine (mean, 53 days versus 90 min) in humans, it may have the potential to provide a longer lasting (and perhaps more effective) effect than lidocaine on neuropathic pain states. IMPLICATIONS: Amiodarone was found to produce a statistically significant decrease in heat, cold, and mechanical hyperalgesia in a rat model of neuropathic pain after intraperitoneal injection. Considering its long half-life in humans, amiodarone has the potential to provide long lasting pain relief in neuropathic pain states.     

静脉输注利多卡因在术后镇痛中的应用

背景 术后疼痛依然是麻醉医师所面临的挑战之一.作为术后镇痛的一线药物,阿片类药物常伴有一些副作用也会影响患者术后的恢复.任何可以减少阿片类药物的用量,并增强术后镇痛效果的多模式术后镇痛方案均推荐用于术后镇痛.研究发现静脉输注利多卡因可以增强术后镇痛效果,降低术后阿片类药物的用量,促进术后胃肠功能的恢复. 目的 现就静脉输注利多卡因对术后镇痛的影响作一综述. 内容 从镇痛机制、药代动力学特点、给药策略以及对不同手术术后镇痛效果的影响等方面分别进行探讨. 趋向 静脉输注利多卡因可以增强腹部术后镇痛效果,减少阿片类药物的用量,但其对其他手术术后镇痛效果的影响及最佳镇痛方案函待进一步研究.     

The antinociceptive effect of local or systemic parecoxib combined with lidocaine/clonidine intravenous regional analgesia for complex regional pain syndrome type I in the arm

We evaluated the efficacy of local or systemic parecoxib combined with lidocaine/clonidine IV regional analgesia in complex regional pain syndrome (CRPS) type 1 in a dominant upper limb. Thirty patients with CRPS type 1 were divided into three groups. The control group (CG) received both IV saline in the healthy limb and IV loco-regional 1 mg/kg of lidocaine + 30 mug of clonidine, diluted to a 10-mL volume with saline. The systemic parecoxib group (SPG) received a regional block similar to that administered to the CG but with systemic 20 mg of parecoxib, whereas the IV regional anesthesia with parecoxib group (IVRAPG) received an extra IV 5 mg of loco-regional parecoxib compared with the CG. The block was performed once a week for 3 consecutive weeks. Analgesia was evaluated by the 10-cm visual analog scale (VAS) and rescue analgesic consumption. The IVRAPG showed less daily ketoprofen (milligrams) consumption in the second and third weeks compared with the other groups (P < 0.05). The IVRAPG also showed less ketoprofen consumption when comparing the first and second week with the third week (P < 0.05). The VAS score comparison among groups revealed that groups were similar during the first and second week observation, although the IVRAPG showed smaller VAS scores in the third week compared with both CG and SPG (P < 0.05). We conclude the IV 5 mg of parecoxib was an effective antiinflammatory drug combined with clonidine/lidocaine loco-regional block in CRPS type 1.