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Background and Objectives: Interleukin-6 (IL-6) is a predictor of trauma severity. The purpose of this study was to evaluate the effect of intravenous lidocaine on pain severity and plasma IL-6 after hysterectomy., Method: A prospective, randomized, comparative, double-blind study with 40 patients, aged 18-60 years. G1 received lidocaine (2mg.kg(-1).h(-1)) or G2 received 0.9% saline solution during the operation. Anesthesia was induced with O2/isoflurane. Pain severity (T0: awake and 6, 12, 18 and 24hours), first analgesic request, and dose of morphine in 24hours were evaluated. IL-6 was measured before starting surgery (T0), five hours after the start (T5), and 24hours after the end of surgery (T24)., Results: There was no difference in pain severity between groups. There was a decrease in pain severity between T0 and other measurement times in G1. Time to first supplementation was greater in G2 (76.0±104.4min) than in G1 (26.7±23.3min). There was no difference in supplemental dose of morphine between G1 (23.5±12.6mg) and G2 (18.7±11.3mg). There were increased concentrations of IL-6 in both groups from T0 to T5 and T24. There was no difference in IL-6 dosage between groups. Lidocaine concentration was 856.5±364.1 ng.mL(-1) in T5 and 30.1±14.2 ng.mL(-1) in T24., Conclusion: Intravenous lidocaine (2mg.kg(-1).h(-1)) did not reduce pain severity and plasma levels of IL-6 in patients undergoing abdominal hysterectomy., (Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.)

Background and Objectives: Some studies showed that ketamine inhibits the production of cytokines. The objective of this study was to evaluate the preemptive analgesic effect of epidural S(+)-ketamine in hysterectomy and plasmatic cytokines (IL-6, TNF-α and IL-10)., Method: A double-blinded study with 29 patients was conducted. Patients in Group 1 received 13 mL of 0.25% bupivacaine with 25mg of S(+)- ketamine 30 minutes before surgical incision and 15 mL of saline solution via the epidural route 30 minutes after. Patients in Group 2 received 15 mL of saline solution 30 minutes before the surgical incision, followed by 13 mL of 0.25% bupivacaine with 25mg of S(+)-ketamine 30 minutes after. Postoperative analgesia was made with epidural bupivacaine and fentanyl. Dipyrone 1 g was used whenever required. The following paramenters were evaluated: concentration of cytokines, intensity of pain, time of first request of analgesic and total quantity of analgesic used., Results: Time for the first request for analgesics was 61.5 minutes in Group 1 and 69.0 in Group 2, without difference between these groups. There was no difference for total dose of fentanyl used in Group 1 (221.4 μg) and Group 2 (223.3 μg). A similar analgesic effect was obtained in both groups, except in T12 (Group 1 = 2.4±3.2; Group 2 = 5.5±3.4). No differences in concentration of cytokines were observed., Conclusions: The epidural injection of 25mg S(+)-ketamine before incision reduced the pain intensity only 12 hours after surgical incision and did not alter concentration of cytokines., (Copyright © 2012 Elsevier Editora Ltda. All rights reserved.)

Background and Objectives: Transcutaneous electrical nerve stimulation (TENS) is commonly used to treat musculoskeletal pain, but it may also be indicated for postoperative analgesia. The objective of this study was to evaluate the analgesic effects of TENS on post-thoracotomy., Methods: Thirty patients between 18 and 60 years of age undergoing thoracotomy for lung cancer resection on the second postoperative day were included in this study. Patients were divided into two groups (G1 and G2). G1 patients were treated with TENS; and in G2 (without TENS) electrodes were placed but the equipment was not turned on. TENS was maintained for one hour. The visual analogue scale was used to evaluate the analgesic effects on three moments: before TENS (M0), immediately after TENS (M1), and one hour later (M2), with the patient at rest, elevation of the upper limbs, change in decubitus, and coughing., Results: The intensity of pain at rest was higher in G2 immediately after TENS, but not one hour after the procedure. There was no difference between both groups with elevation of the upper limbs, decubitus change, and coughing., Conclusions: With the use of TENS for one hour on the second post-thoracotomy day in patients who received fentanyl (50 μg) associated with bupivacaine (5 mL), a reduction in pain intensity was observed at rest immediately after TENS; with elevation of the upper limbs, change in decubitus, and coughing, a reduction in pain severity was not observed., (Copyright © 2011 Elsevier Editora Ltda. All rights reserved.)

Background and Objectives: Cytokines are necessary for the inflammatory response, favoring proper wound healing. However, exaggerated proinflammatory cytokine production can manifest systemically as hemodynamic instability or metabolic derangements. The objective of this review was to describe the effects of cytokines in pain., Contents: This article reviews the effects of cytokines in pain. In diseases with acute or chronic inflammation, cytokines can be recognized by neurons and used to trigger several cell reactions that influence the activity, proliferation, and survival of immune cells, as well as the production and activity of other cytokines. Cytokines can be proinflammatory and anti-inflammatory. Proinflammatory cytokines are related with the pathophysiology of pain syndromes. Cells that secrete proinflammatory (IL-1, IL-2, IL-6, IL-7, and TNF) and anti-inflammatory (IL-4, IL-10, IL-13, and TGFβ) cytokines, the functions of each cytokine, and the action of those compounds on pain processing, have been described., Conclusions: Cytokines have an important role in pain through different mechanisms in several sites of pain transmission pathways., (Copyright © 2011 Elsevier Editora Ltda. All rights reserved.)

Background and Objectives: Chronic pain is very prevalent and the cost of its treatment can cause a relevant impact on people and society. The objective of this study was to evaluate the monthly cost of drugs used in the outpatient treatment of chronic pain., Methods: In the present study the cost of the drugs used by 233 patients with chronic pain (117 with nociceptive pain, 59 with neuropathic pain, and 57 with mixed pain) followed at the Alpha Center of UNIFESP between January 2004 and January 2008 was evaluated., Results: The mean general cost was R$ 127.74 (from R$ 5.00 to R$ 780.00)., Conclusions: This study showed that the cost of the drugs does not differ significantly taking into consideration the type of pain., (Copyright 2010 Elsevier Editora Ltda. All rights reserved.)

Background and Objectives: Most patients undergoing surgery experience moderate to severe pain, indicating the need to improve the anesthetic technique. Intravenous lidocaine has been widely used in the treatment of chronic pain. The objective of this report was to review the use of intravenous lidocaine for postoperative analgesia., Contents: The pharmacologic aspects and mechanism of action of lidocaine as well as clinical studies in which the authors used intraoperative lidocaine were reviewed., Conclusions: Intravenous lidocaine can promote analgesia in surgical procedures, representing another alternative for the treatment of acute pain. Controlled studies with different surgical interventions could bring more information on this modality of analgesia., (Copyright 2010 Elsevier Editora Ltda. All rights reserved.)

Background and Objectives: Neurological evaluation can be done during cervical plexus block for endarterectomy, which also maintains postoperative analgesia. The objective of this study was to compare the analgesic effects of clonidine associated with bupivacaine to those of bupivacaine in cervical plexus block., Methods: A randomized double-blind study was undertaken with 30 patients divided in two groups: G1 received 1.5 mg.kg-1 of 0.375% bupivacaine associated with 150 (1/4)g of clonidine (2 mL), and G2 received 1.5 mg.kg-1 of 0.375% bupivacaine associated with NS (2 mL). The following parameters were evaluated: heart rate and blood pressure at 0 (block), 30, 60, 90, and 120 minutes; the need for anesthetic supplementation; time until the first analgesic supplementation; amount of analgesic used; and pain severity at 0 (end of the surgery), 30, 60, 120, 240, and 360 minutes., Results: Group 1 received 3.8 mL of lidocaine for anesthetic supplementation, while G2 received 3.6 mL of lidocaine, but this difference was not statistically significant. In G1, the time until the first supplementation was 302.6 +/- 152.6 minutes, and in G2 it was 236.6 +/- 132.9 minutes, which was not statistically significant. Differences between the doses of dypirone and tramadol were not observed. Differences in pain severity between both groups were not observed either., Conclusion: The association of 150 (1/4)g of clonidine and bupivacaine in cervical plexus block for carotid endarterectomy did not improve significantly the analgesic effects evaluated by pain severity, time until the first analgesic supplementations and amount of supplementary analgesics.

Background and Objectives: Trigeminal neuralgia is an extremely painful condition characterized by recurrent episodes of sudden, lancinating, shock-like pain lasting from a few seconds to two minutes usually unilateral. It has an annual incidence of approximately 4.3 in 100,000 in the general population and only 3% of those cases present bilateral manifestation. The objective of this report was to describe a rare case of bilateral trigeminal neuralgia., Case Report: A 61 years old housewife from Maranhão, Brazil, married, with a history of hypertension, presented with a six-year history of severe pain in the left V2-V3 regions, lasting 5 to 10 seconds, in the lateral aspect of the nose and mandible, worsening by talking, chewing, and with a decrease in temperature. She had been treated with chlorpromazine (3 mg every eight hours) and carbamazepine (200 mg every eight hours) during six months without improvement. On physical exam, the patient presented thermal and mechanical allodynia in the V2-V3 regions. She was using gabapentin (1,200 mg/day) with partial relief of the pain. The dose of gabapentin was increased to 1,500 mg/day and amitriptyline 12.5 mg at night was added to the therapeutic regimen. The patient evolved with mild and sporadical pain and a reduction in pain severity during 10 months; the dose of gabapentin was progressively reduced to 600 mg/day, and amitriptyline was maintained at 12.5 mg/day. After one year, the patient developed similar pain in the region of the right mandible, which improved with an increase in the dose of gabapentin to 900 mg/day. Head CT and MRI did not show any abnormalities., Conclusions: Carbamazepine is the first choice for the treatment of trigeminal neuralgia; however, the use of gabapentin as the first pharmacological choice or in cases refractory to conventional therapy has been increasing.

Background and Methods: Proinflammatory cytokines play an important role in the pathophysiology of neuropathic pain syndromes. The objective of this study was to evaluate plasma levels of proinflammatory cytokines before and after treatment with tramadol in patients with herniated intervertebral disks and carpal tunnel syndrome, and to compare them with normal individuals., Methods: Thirty-eight patients with neuropathic pain secondary to herniated intervertebral disks or carpal tunnel syndrome participated in this study. All patients were treated with controlled release tramadol (100 mg every 12 hours) for 10 days. Venous blood (5 mL) was collected in the morning, before treatment and on the 11th day, and stored (-70 degrees C) until analysis. ELISA was used to determine the plasma levels of cytokines (TNF-+/-, IL-1, IL-6) and receptors sTNF-R1 (R & D Systems). Plasma levels of cytokines of 10 healthy volunteers were also determined., Results: The concentration of TNF-+/- before (5.8 +/- 2.8 pg.mL-(1)) was significantly higher than after treatment with tramadol (4.8 +/- 2.1 pg.mL-1; p = 0.04, Mann-Whitney test). The levels of IL-1(2), IL-6, and sTNF-R1 before and after treatment with tramadol showed no significant differences. Plasma levels of TNF-+/- (healthy individuals: 1.4 +/- 0.5; pain patients: 5.8 +/- 2.8 pg.mL-1; p = 0.01) and IL-6 (healthy individuals: 1.2 +/- 0.8; pain patients: 3.5 +/- 2.6 pg.mL-1; p = 0.01) were significantly higher in patients with neuropathic pain, Mann-Whitney Test., Conclusions: In patients with herniated intervertebral disks and carpal tunnel syndrome, plasma levels of TNF-+/- and IL-6 were higher than in healthy volunteers, while differences in the concentrations of sTNF-R and IL-1(2) were not observed. Plasma levels of TNF-+/-, but not of IL-6, sTNF-R, and IL-1(2), decreased after treatment with tramadol (100 mg every 12 hours).

Background and Objectives: Gabapentin has been used as adjuvant in the treatment of postoperative pain with a neuropathic component. It is responsible for the inhibition of central sensitization, decreasing postoperative pain., Contents: All clinical, randomized studies that evaluated the effects of gabapentin on postoperative pain in humans between 2002 and 2007 for a total of 26 studies were selected. In 17 studies, patients received a single preoperative dose, which ranged from 300 to 1,200 mg, 30 minutes to two hours before surgery in the remaining studies, the administration of the drug was initiated one to 24 hours before the procedure and continued for 10 days, in doses that ranged from 1,200 to 1,800 mg.day(-1). To measure pain severity, the Visual Analog or Numeric Rating Scale was used. In 75% of patients who received a single dose of gabapentin, scores were lower, and the same was seen in 55.6% of patients who received the drugs pre- and postoperatively. Opioid consumption was reduced in 82.4% of patients who received a single dose, and in 77.8% of patients who received pre- and postoperative gabapentin. Among the studies using a single dose of gabapentin, four did not describe adverse effects; 52.9% showed no differences, 11.8% detected more nausea or vomiting, 5.9% experienced more dizziness, 5.9% more sedation, less nausea or vomiting in one, and less urinary retention in one. Among the studies with pre- and postoperative administration of gabapentin, four did not describe adverse effects; 22.2% showed no differences, 11.1% had more nausea or vomiting, 22.2% more dizziness, and 11.1% more sedation., Conclusions: Gabapentin, used before as well as before and after surgery, decreased pain severity and the need of analgesic supplementation.

Background and Objectives: Morphine is used frequently to treat oncologic pain. However, tolerance may develop with prolonged use. The association of a NMDA receptor antagonist may reduce or delay the onset of tolerance. S(+) ketamine seems to be more potent and with fewer side effects. The aim of this study was to evaluate the association of S(+) ketamine and morphine in the treatment of oncologic pain., Methods: Thirty patients, randomly divided in two groups, participated in this double-blind study. Patients in G1 received 10 mg of morphine PO every 6 hours and 10 mg of S(+) ketamine PO every 8 hours. Patients in G2 received 10 mg of morphine PO every 6 hours and placebo PO every 8 hours. The dose of morphine was adjusted by 5 mg increments whenever necessary. Pain severity was evaluated through a verbal scale., Results: The percentage of no pain and mild pain was similar in both groups (G1 = 0 and G2 = 0 at M0; G1 = 22.2 and G2 = 53.8 at M1; G1 = 22.2 and G2 = 61.5 at M2; G1 = 44.6 and G2 = 61.5 at M3; and G1 = 44.5 and G2 = 53.8 at M4); Chi-square test. The percentage of moderate relief and complete relief was similar in both groups (G1 = 33.4 and G2 = 53.9 after one week; G1 = 44.4 and G2 = 69.2 after two weeks; G1 = 66.6 and G2 = 69.2 after three weeks; and G1 = 55.6 and G2 = 53.9 after four weeks); Chi-square test. The need to increase the dose of morphine was also similar in both groups (G1 = 2.22 and G2 = 2.15); Mann-Whitney test., Conclusions: We did not observe an increase on the analgesic effects of morphine with the association of 10 mg of S(+) ketamine PO in the treatment of oncologic pain.

Background and Objectives: Osteoarthritis is the most common joint disease among elderly people. This study aimed at comparing the analgesic effects of intra-articular bupivacaine and morphine in knee osteoarthritis patients., Methods: Thirty-nine patients were included in this randomized double-blind study and divided in two groups: G1 (n = 18) patients were given intra-articular 1 mg (1 mL) morphine diluted in 9 mL of 0.9% saline, while G2 (n = 21) received intra-articular 25 mg (10 mL) of 0.25% plain bupivacaine. Pain intensity was evaluated by numerical and verbal scale at 0, 30, 60 minutes and 7 days at rest and in movement. Evaluated parameters were analgesic supplementation requirement with paracetamol (500 mg), total analgesic dose throughout the study, analgesia duration and quality (according to patient)., Results: From 39 patients, 31 have completed the study. There has been no significant difference in pain intensity at rest and in movement between groups in all studied moments. There has been no difference between groups in time between solution administration and need for analgesic supplementation. Mean paracetamol dose in the first day was 796 mg for G1 and 950 mg for G2; supplementation during the week was 3578 mg for G1 and 5333 mg for G2., Conclusions: The analgesic effect of intra-articular 1 mg morphine and 25 mg of 0.25% plain bupivacaine was similar.

Background and Objectives: There are controversies about the efficacy of botulin toxin as compared to local anesthetics for triggering-points infiltration. This study aimed at comparing the analgesic effect of botulin toxin and bupivacaine for triggering-points infiltration in chronic myofascial syndrome., Methods: Participated in this study 20 patients divided in two groups. G1 patients (n = 10) received 25U botulin toxin and G2 patients (n = 10) received 0.25% bupivacaine in one to three triggering-points, being 0.5 mL per point. Patients were weekly evaluated for 8 weeks. Orphenadrine (35 mg) and dipirone (300 mg) were associated every 8 hours and patients were submitted to transcutaneous electrical stimulation twice a week during 1 hour. Pain intensity was evaluated through verbal numeric scale and quality of analgesia was evaluated by patients in moments zero (before injection), 30 minutes after, and at 1, 2, 3, 4, 5, 6, 7 and 8 weeks. Results were submitted to statistical analysis (Mann-Whitney and Fisher Exact tests)., Results: After 30 minutes, 1 and 4 weeks, pain intensity was lower for G1 as compared to G2. After 2, 3, 5, 7 and 8 weeks, there was no significant difference between groups. Quality of analgesia was considered better by G1 patients as compared to G2, except after 2 weeks., Conclusions: Analgesic effect was better with botulin toxin (25U) as compared to 0.25% bupivacaine for triggering-points infiltration.

Unlabelled: BACKAGROUND AND OBJECTIVES: Since the finding that ketamine blocks NMDA receptors in the neurons of spinal dorsal horn, it has been used to inhibit or decrease central sensitization triggered by nociceptive stimulations. This study aimed at presenting pharmacological aspects of racemic ketamine and its levogyrous compound, as well as its usefulness for preemptive analgesia., Contents: Current preemptive analgesia concepts, pharmacological aspects of ketamine and its levogyrous compound, as well as experimental and clinical trials on ketamine and its use in preemptive analgesia are presented., Conclusions: The efficacy of ketamine in inhibiting or decreasing central sensitization triggered by nociceptive stimulations is not totally confirmed, probably due to different study and statistical analysis methods.

Background and Objectives: There are controversies about the action site of lipophylic opioids after epidural injection. Some authors believe that these drugs act at supraspinal level, while others propose a spinal action. This comparative study aimed at answering this question by comparing epidural and intravenous fentanyl for postoperative analgesia of lower limb orthopedic procedures., Methods: This was a randomized double-blind study. At postoperative pain complaint, G1 patients (n = 14) received 5 mL epidural solution (100 microg fentanyl in 0.9% saline) and 2 mL of intravenous 0.9% saline; G2 patients (n = 15) received 5 mL epidural 0.9% saline and 2 mL intravenous fentanyl (100 microg). Analgesic complementation with intravenous tenoxicam (40 mg) and epidural 0.25% bupivacaine (5 mL) (when there was no relief with tenoxicam) has been evaluated. Pain intensity was evaluated by numeric and verbal scales in moments M30, M120 and M240 minutes., Results: Number of patients needing analgesic complementation both with tenoxicam (G1 = 10 and G2 = 15 patients) and bupivacaine (G1 = 2 and G2 = 8 patients) has been higher in G2. There have been no statistical differences in pain intensity between groups in all studied moments., Conclusions: In the conditions of our study, effects of epidural fentanyl were better as compared to intravenous fentanyl.

Background and Objectives: Spinal morphine promotes good pain relief, but is not free from side effects. This study aimed at verifying the correlation between CSF morphine concentration and side effects., Methods: This study involved 4 groups of 7 rats, which were studied 24 hours after spinal catheter insertion via cisterna magna. Groups G1, G2, G3 and G4 received respectively 0.1; 0.3; 0.5 and 1 microg morphine in 10 microl of 0.9% saline solution. CSF samples were collected and side effects were recorded at M15, M30, M60, M120 and M180 minutes after injection., Results: Side effects observed were: mandible tremors, agitation, pruritus, absence of diuresis, sedation, and respiratory changes. The incidence of side effects was higher during early evaluations and progressively decreased with time. Mean CSF morphine concentrations in G1 varied from 72.84 to 1.13 pg; in G2 from 114.26 to 5.68 pg; in G3 from 151.18 to 13.62 pg and in G4, from 561.37 to 18.61 pg., Conclusions: There has been no correlation between CSF morphine concentration and side effects.

Background and Objectives: Spinal morphine promotes adequate pain relief, but is not free from side effects. This study aimed at investigating the effects of different spinal morphine doses., Methods: Five groups of seven rats were studied, 24 h after spinal catheter insertion via cisterna magna under anesthesia with muscular ketamine and xylazine. G1 received 10 microl saline solution; groups G2, G3, G4 and G5 received respectively 0.1; 0.3; 0.5 and 1 microg morphine in 10 microl saline solution. Animals were submitted to tail immersion test in hot water at M0 (prior to injection), and M15, M30, M60, M120 and M180 minutes after the injection., Results: Analgesic effects were observed in groups receiving morphine, in different times, as compared to control and to time before morphine injection. In G1 there was paws weakness in 4 animals. Agitation was observed at M15 in G2 and at M15 and M30 in G3. Mandible tremors were observed at moments M5, M15, M30 and M60 in G2; at M5 and M15 in G3, in M5 in G4, and in M5 in G5. Pruritus was observed at M5, M15, M30 and M60 in G2; at M5, M15, M30, M60 and M120 in G3; at M5, M15, M30, M60, and M120 in G4; and at M5, M15, M30, M60 and M120 in G5. Absence of diuresis was observed at M60 in G2; at M15, M30, M60 and M120 in G3; at M30 and M120 in G4, and at M30, and M60 in G5. Sedation was observed at M15, M30 and M60 in groups 2, 3 and 4; and at M15, M30, M60 and M120 in G5. Respiratory changes were observed at M15, M30 and M60 in G2; at M15, M30 and M60 in G3; at M15 and M30 in groups 4 and 5., Conclusions: In this study all morphine doses below 1 microg have promoted short duration analgesia; all spinal morphine doses have produced side effects.

Background and Objectives: In spite of the frequent use of high doses of fentanyl for major surgeries, the correlation of its residual plasma concentration to postoperative analgesia deserves further investigation. This study aimed at evaluating the residual analgesic effect of fentanyl in the first and second postoperative days of myocardial revascularization, as well as quantifying its concentration., Methods: Participated in this study 11 patients undergoing myocardial revascularization with cardiopulmonary bypass under general anesthesia with 50 microg.kg-1 intravenous fentanyl. Analgesia was evaluated by a numeric verbal scale at moments zero (extubation), 70 min, 3, 5, 8 and 12 hours in the first day; and moments zero (24 h after extubation), 70 min, 3, 5, 8 and 12 hours in second post-operative day. Pain intensity to vigorous cough and respiratory physical therapy was evaluated. At every measurement, patients were asked about the need for analgesic complementation. Plasma samples were collected in moments zero (extubation), 70 min, 3, 5, 8 and 12 hours during the first and second postoperative days for fentanyl radioimmunoassay., Results: Mean pain intensity varied from 1.9 to 3.7 in the first day and from 2.1 to 3.8 in the second postoperative day. Fentanyl plasma levels (> 1 ng/ml) evidenced its contribution to post-operative analgesia during the first postoperative day., Conclusions: In spite of the lack of correlation between residual fentanyl plasma concentration and pain intensity, patients referred only mild pain during the whole investigation period.

Background and Objectives: Methods to promote knee pain analgesia without impairing motor function have been widely researched. This study aimed at comparing intra-articular morphine, bupivacaine, and fentanyl analgesic effects (as compared to saline solution), after knee video-arthroscopy., Methods: Participated in this study 60 patients who were randomly distributed in four groups: GI (n = 15) 10 ml saline solution; GII (n = 15) 2 mg morphine diluted in 10 ml saline solution; GIII (n = 15) 10 ml of 0.25% bupivacaine; GIV (n = 15) 100 microg fentanyl diluted in 10 ml saline solution, injected at surgery completion. All patients received spinal anesthesia with 15 mg hyperbaric bupivacaine. Pain intensity was evaluated by a visual analog scale (VAS) (at surgery completion, and 6, 12, 18 and 24 hours later). The need for analgesic complementation (1 g intravenous dipirone) was also evaluated. Side effects were recorded., Results: There were no statistical differences in pain intensity among groups in almost all moments studied. There was a statistic difference up to 6 hours, when the fentanyl group had significantly lower pain. The morphine group needed more dipirone complementation. Side effects were minor, without statistical significance., Conclusions: There were no statistical differences among solutions analgesic effects in almost all moments studied.