Lidocaine, a widely used local anaesthetic, has been shown to possess anti-inflammatory and immunomodulatory properties with applications in surgery. During a surgical procedure, inflammation is a natural response of the body, triggered by the release of inflammatory mediators and the activation of the immune system. However, an excessive response can lead to serious postoperative complications. Lidocaine modulates inflammation through mechanisms beyond its anaesthetic action. It reduces the activation of neutrophils and macrophages, decreases the release of pro-inflammatory cytokines and prostaglandins, and preserves endothelial integrity, helping to control excessive inflammatory responses. Additionally, its perioperative use has shown benefits such as reduced postoperative pain, lower opioid consumption, and faster intestinal recovery. Furthermore, studies have suggested that lidocaine may have an anti-metastatic effect by inhibiting the migration of tumour cells and the activation of inflammatory pathways related to cancer spread. Although its use in surgery is promising, further research is needed to determine optimal dosages and its long-term clinical impact.

Management of procedural pain in burn care is challenging. Lidocaine-prilocaine cream 5%, eutectic mixture of local anesthetics (EMLA®), is a widely used, effective local anesthetic cream approved for normal intact skin, genital mucosa for superficial surgical procedures, and debridement of chronic leg ulcers. This comprehensive review aimed to determine the safety, analgesic efficacy, and effects of EMLA on burn pathophysiology to provide evidence-based clinical recommendations for introducing the topical anesthetic into burn care.

The PRISMA guidelines were followed for conducting a systematic PubMed search to include all relevant preclinical and clinical studies, according to pre-specified eligibility criteria.

Fifteen studies were included in a qualitative synthesis, among which nine were human and six were animal studies. To date, safety and pharmacokinetic data on EMLA application in burns have been limited. Nevertheless, human studies indicated that EMLA is safe and provides adequate procedural-pain relief in adults when applied to smaller burns. Caution should be exercised when using EMLA in younger children, as systemic toxicity, pertaining to prilocaine-induced methemoglobinemia, has been reported owing to overdosing (high doses applied over large burn areas). Furthermore, animal studies demonstrate the potential beneficial effects of EMLA on burn pathophysiology such as anti-inflammatory, decreased capillary permeability to plasma proteins and edema formation, and improved tissue perfusion, which are factors that may impact burn wound progression.

Current data on EMLA use in the management of procedural pain in small burns are sparse but suggest that EMLA is safe and effective in adults. Further clinical pharmacokinetic studies are warranted, especially for application on larger burn areas.

Recent evidence suggests that locally delivered local anesthetics may exert tissue-damaging effects such as chondrolysis after intraarticular injection. Alteration of the inflammatory response is a potential mechanism for local anesthetic-induced tissue toxicity. In this study, we tested the effects of continuous local anesthetic infiltration on the release of inflammatory and nociceptive mediators in skin wounds after cesarean delivery.

Thirty-eight healthy women undergoing cesarean delivery with spinal anesthesia were enrolled in this study, and were randomized to receive subcutaneous surgical wound infiltration with bupivacaine 5 mg/mL or saline at 2 mL/h for 24 hours after cesarean delivery. Wound exudate was sampled at 1, 3, 5, 7, and 24 hours after cesarean delivery using a subcutaneous wound drain technique. Cytokines, chemokines, substance P, prostaglandin E(2), and nerve growth factor were assayed using multiplex Bio-Plex® (Bio-Rad, Hercules, CA) and enzyme-linked immunosorbent assays.

Bupivacaine wound infusion resulted in a significant decrease of interleukin 10 and increase of substance P in wounds compared with saline infusion (area under the 24-hour concentration-time curve; P < 0.001). No statistically significant differences were detected for other cytokines, nerve growth factor, and prostaglandin E(2).

This study demonstrates that the continuous administration of clinically used doses of bupivacaine into wounds affects the local composition of wound mediators. Observed changes in interleukin 10 are compatible with a disruption of antiinflammatory mechanisms. Whether such modulation combined with the release of the proinflammatory mediator substance P results in an overall proinflammatory wound response will require future studies of wound healing.

Peripheral inflammatory pain is associated with an upregulation of spinal cord COX-2 (cyclooxygenase-2), with a subsequent increase in central prostaglandin E2 (PGE2) levels associated with the development of hyperalgesia. In this study, we evaluated the effect of bupivacaine administered via a nerve block or via a systemic route on the spinal expression of PGE2 and COX in a model of peripheral inflammation in rats.

All rats randomly received three injections: 1) a left subcutaneous hindpaw injection (0.2 mL with either carrageenan 2% w/v or saline), 2) a left sciatic block (0.2 mL with either bupivacaine 0.5% or saline), and 3) a systemic injection (subcutaneous interscapular with 0.2 mL with either bupivacaine 0.5% or saline). Local edema, thermal, and mechanical hyperalgesia as well as cerebrospinal fluid PGE2 concentration and COX-1 and COX-2 expression in the spinal cord in dorsal root ganglions were measured.

We confirmed that a bupivacaine block attenuates hyperalgesia and local inflammation in a model of inflammatory pain. This effect was associated with an inhibition of the increase in COX-2 expression induced by peripheral inflammation in dorsal root ganglions and cord. The subsequent production of PGE2 in cerebrospinal fluid was also impaired. Systemic bupivacaine did not modify either the hyperalgesia and local inflammation or COX expression.

These results constitute a key element strongly suggesting that local anesthetics act at a different level when administered systematically or via a nerve block.

To investigate existence of evidence that supports the therapeutical use of lidocaine as an anti-inflammatory substance.

A search on health sciences databases was performed, including only papers published in English until May 2007 which reported in vivo experimental studies that tested lidocaine as an anti-inflammatory substance and used morphological and/or biochemical analysis. The keywords used were: "lidocaine & inflammation", "lidocaine & neutrophils" and "lidocaine & prostaglandin". The search results were previous selected by title and abstract, and then articles were read and those that met inclusion criteria were carefully analyzed and classified.

Only 10 articles met the inclusion criteria, and were carefully read. They were ranked (A, B, and C) according to the level of evidence produced. Seven articles were classified as C, two classified as B, and one classified as A. Despite methodological differences, all of them, except for one, reported that lidocaine showed anti-inflammatory effects.

According to the reviewed literature, lidocaine has a potential as an anti-inflammatory agent. However, there is still a lack of well-designed studies to support its clinical use, and none of them evaluated its effects on a mucous epithelium.

Development of new local anesthetic agents has been focused on the potency of their nerve-blocking effects, duration of action and safety and has resulted in a substantial number of agents in clinical use. It is well established and well documented that the nerve blocking effects of local anesthetics are secondary to their interaction with the Na+ channels thereby blocking nerve membrane excitability and the generation of action potentials. Accumulating data suggest however that local anesthetics also possess a wide range of anti-inflammatory actions through their effects on cells of the immune system, as well as on other cells, e.g. microorganisms, thrombocytes and erythrocytes. The potent anti-inflammatory properties of local anesthetics, superior in several aspects to traditional anti-inflammatory agents of the NSAID and steroid groups and with fewer side-effects, has prompted clinicians to introduce them in the treatment of various inflammation-related conditions and diseases. They have proved successful in the treatment of burn injuries, interstitial cystitis, ulcerative proctitis, arthritis and herpes simplex infections. The detailed mechanisms of action are not fully understood but seem to involve a reversible interaction with membrane proteins and lipids thus regulating cell metabolic activity, migration, exocytosis and phagocytosis.

Rofecoxib, a selective cyclooxygenase-2 inhibitor, and dexketoprofen trometamol, a single isomer non-steroidal anti-inflammatory drug (NSAID), are available for the treatment of acute pain. Both are claimed to have fewer adverse effects than traditional NSAIDs. We have compared them in a clinical setting.

We performed a double-blind randomized controlled trial involving 120 patients undergoing surgical removal of a single mandibular third molar at the Edinburgh Dental Institute. Those who developed moderate pain within 4 h of the procedure were allocated to one of three groups: rofecoxib 50 mg (Group RO, n=37); dexketoprofen trometamol 25 mg (Group DE, n=42); or placebo (Group PL, n=41). Participants monitored pain intensity and pain relief for 24 h using visual analogue scales (VAS) and verbal rating scales (VRS). The summed, time-weighted pain relief score to 8 h derived from the VRS (TOTPAR 8) was used as the primary outcome variable.

No significant difference was demonstrated between Groups RO and DE using TOTPAR 8 as the primary outcome variable. Both drugs were significantly different compared with placebo. Rescue analgesia during the trial period was required by only 15 out of 37 subjects in Group RO, but 35 out of 42 subjects in Group DE. The median times to use of rescue medication were 150 (Group PL), 398 (Group DE) and 1440 min (Group RO). Both drugs were well tolerated and adverse events reported were mild to moderate in severity.

Rofecoxib and dexketoprofen trometamol are effective treatments for acute pain using a dental pain model and are well tolerated. Rofecoxib has a longer duration of action as a single dose and gave adequate analgesia for over half of that study group; patients in the dexketoprofen trometamol group needed more rescue analgesia.

Major burns are associated with multiple internal organ damages, including necrosis of the gastrointestinal mucosa. Failure of the intestinal barrier is a serious complication in burned patients. Epidermal growth factor (EGF) is a mitogenic polypeptide that stimulates wound repair and affords protection to the gastric mucosa. We examined whether a single systemic intervention with EGF prevents organ systems damages, following full-thickness scalds (25-30%) in rodents. Animals were randomly assigned to receive an intraperitoneal injection of EGF (30 microg/kg in mice, 10 microg/kg in rats) or saline solution, 30 min prior thermal injury in mice or after the cutaneous injury in rats. General clinical condition and mortality during 24h were recorded. Animals were autopsied and histopathological and histomorphometric studies were conducted. Mice treated with EGF exhibited a milder clinical evolution and acute lethality was significantly reduced as compared to saline counterparts (P<0.01). Histopathological and morphometric analysis showed that EGF significantly reduced intestinal necrosis and contributed to preserve jejunoileal architecture in mice (P<0.05) and rats (P<0.01). The onset of renal hemorrhagic foci was significantly reduced in EGF-treated groups (P<0.01). Lung damages appeared attenuated in EGF-treated animals. These data indicate the salutary effects of EGF by attenuating internal complications associated to thermal injuries. Further studies are warranted to fully elucidate the usefulness of this therapy.

Few techniques today enable us to measure the complex processes taking place inside a burn wound in vivo. The present in vivo technique was based on a standardised burn model in rat skin. A partial- or full-thickness burn was induced and resulted in a gelatinous oedema located between the skin and the underlying rectus muscle. The oedema has distinct borders to the surrounding connective tissue and is separated and removed easily for further analysis. Myeloperoxidase (MPO) activity used as indicator of neutrofil infiltration was increased significantly in the burn oedema versus non-burned skin. Leukocyte metabolic activity was high as shown by significantly higher free radical formation (ESR) in the oedema than in surrounding burned and non-burned tissue. Leukocyte viability measured by Trypan blue stain was 70% in the oedema of full-thickness burns. In order to decide whether processes taking place in the oedema communicate freely with systemic circulation, we conducted a number of experiments. Results show in burned animals in vivo that intravenous administration of indomethacin induced a strong inhibition of PGE(2) in the burn oedema as compared with saline but, as expected, had no significant effect on LTB(4) synthesis. In conclusion, the present technique allows us to analyse the processes taking place inside the burn wound in vivo and to evaluate the effects of various agents on these processes.

Vasoactive intestinal polypeptide has been demonstrated to lack inherent effects on capillary permeability, but also to potentiate the oedema promoting actions of other inflammatory mediators or even to strongly reduce organ damage and subsequent oedema in ischemic models of the lung and heart. This study investigated the role of VIP on oedema in partial- and full-thickness skin burns of anaesthetised rats in vivo by spectrophotometrical quantification of Evans blue albumin. Results show that systemic VIP elicited a significant drop in mean arterial blood pressure versus saline (p<0. 001) and VIP antiserum (p<0.001) both in burned and non-burned animals. VIP also decreased heart rate versus saline (p<0.05) and anti-VIP (p<0.01) in non-burned and burned animals. EB-albumin in normal skin was significantly inhibited by VIP as compared to saline (p<0.05), but did not differ significantly from VIP-antiserum. A significant inhibition of EB-albumin extravasation versus saline was also seen following administration of VIP-antiserum (p<0.01). Similarly, VIP significantly reduced EB-albumin extravasation versus saline treatment in partial-thickness (p<0.01) and full-thickness burns (p<0.001), while VIP-antiserum had no significant effect on skin perfusion in any of the burned groups as compared to saline treatment. The present results show that systemic VIP is a potent inhibitor of burn oedema. This effect could be secondary to constriction of skin vessels as a result of VIP-induced systemic hypotension or be mediated by the interaction of VIP with other oedema promoting mediators released following a thermal trauma to the skin.