First-degree Burn Research Articles

Methylprednisolone and ketorolac rapidly reduce hyperalgesia around a skin burn injury and increase pressure pain thresholds

Glucocorticoids and non-steroidal anti-inflammatory drugs (NSAIDs) decrease acute postoperative pain and hyperalgesia. The objectives of this study were to investigate the effects of methylprednisolone and ketorolac on hyperalgesia around a skin burn injury and on pressure pain thresholds. In a double-blind, placebo-controlled, randomized trial with cross-over design, methylprednisolone 125 mg, ketorolac 60 mg or placebo was administered intravenously in 12 male volunteers on three separate days at least 4 days apart. Primary and secondary hyperalgesia were produced by a first-degree burn injury on abdominal skin 45 min before injection of the test medicines. The area of secondary mechanical hyperalgesia outside the site of injury was measured. Pressure pain stimuli were applied on the base of a fingernail, increasing until the pressure pain detection threshold (PPDT) and pressure pain tolerance threshold (PPTT) were reached. Compared with placebo, the active drugs reduced the area of secondary hyperalgesia (methylprednisolone, P < 0.001; ketorolac, P < 0.01). Ketorolac but not methylprednisolone increased PPDT compared with placebo (P < 0.05). Both active drugs increased PPTT compared with placebo (methylprednisolone, P < 0.01; ketorolac, P < 0.001). Ketorolac increased PPTT more than methylprednisolone (P < 0.05). Methylprednisolone and ketorolac increased PPTT attenuated secondary hyperalgesia around a skin burn injury. PPTT increased after both methylprednisolone and ketorolac. The present study demonstrates analgesic and anti-hyperalgesic properties of a glucocorticoid and a non-selective NSAID that have not been demonstrated previously in human subjects.

Frequently Missed Office Procedures: Are You Capturing What You Perform?

Frequently Missed Office Procedures: Are You Capturing What You Perform?

Calcium-Permeable α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/Kainate Receptors Mediate Development, but Not Maintenance, of Secondary Allodynia Evoked by First-Degree Burn in the Rat

Intrathecal pretreatment with N-methyl-D-aspartate (NMDA) receptor antagonists blocks development of spinal sensitization in a number of pain models. In contrast, secondary mechanical allodynia evoked by thermal injury (52.5 degrees C for 45 s) applied to the hind paw of the rat is not blocked by intrathecal pretreatment with NMDA receptor antagonists. It is, however, blocked by antagonists to the non-NMDA, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate (AMPA/KA) and calcium-permeable AMPA/KA receptors. These findings suggest a role for these receptors in the development of spinal sensitization. The present study used the same thermal injury model to assess the effects of the AMPA/KA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and specific calcium-permeable AMPA/KA receptor antagonists philanthotoxin (PHTx) and joro spider toxin (JST) when given as postinjury treatments. Intrathecal saline injection at 5 and 30 min postinjury had no effect on thermal injury-evoked allodynia as measured by calibrated von Frey filaments. In contrast, 36 nmol of CNQX given at either time point reversed allodynia. Intrathecal 13 nmol of PHTx or 9 nmol of JST (higher doses than that required for pretreatment) reversed allodynia at the 5-min time point, but neither drug was antiallodynic at the 30-min time point. Thus, secondary mechanical allodynia in this model is not maintained by calcium-permeable AMPA/KA receptors, but instead requires activation of calcium-impermeable AMPA/KA receptors. This finding supports a role for AMPA/KA receptor function in responses occurring during spinal sensitization.

This Month in ANESTHESIOLOGY

This Month in ANESTHESIOLOGY

Analgesic effects of dexamethasone in burn injury

Background and Objectives: Glucocorticoids are well-known adjuvant analgesics in certain chronic pain states. There is, however, a paucity of data on their analgesic efficacy in acute pain. Therefore, the aim of the study was to examine the analgesic effects of dexamethasone in a validated burn model of acute inflammatory pain in humans. Methods: Twenty-two volunteers were investigated in a double-blind, randomized, placebo-controlled cross-over study. Intravenous dexamethasone 8 mg or placebo was administered on 2 separate study days. Two hours after drug administration, a first-degree burn injury was produced on the medial aspect of the nondominant calf (12.5 cm2, 47°C for 7 minutes). Quantitative sensory testing included pain ratings to thermal and mechanical stimuli (visual analog scale [VAS]), assessments of thermal and mechanical detection thresholds, and areas of allodynia and secondary hyperalgesia. Results: The burn injury induced significant increases in erythema (P < .0001) and hyperalgesia (P < .001) in both groups. Pain ratings and development of tactile allodynia during the burn did not differ between dexamethasone and placebo treatments (P > .6). There were no significant differences between treatments in regard to skin erythema (P > .8), thermal or mechanical thresholds (P > .2), thermal or mechanical pain response (P > .2), or mechanical secondary hyperalgesia (P > .2). Dexamethasone had no analgesic effects in normal skin. Conclusions: The study indicates that systemic administration of dexamethasone 2 hours before a burn injury does not reduce the inflammatory-mediated changes in quantitative sensory thresholds, pain perception, or skin erythema in humans. Reg Anesth Pain Med 2002;27:254-260.

Effects of gabapentin in acute inflammatory pain in humans

Background and Objectives: The aim of the study was to examine the analgesic effects of the anticonvulsant, gabapentin, in a validated model of acute inflammatory pain. Methods: Twenty-two volunteers were investigated in a double-blind, randomized, placebo-controlled cross-over study. Gabapentin 1,200 mg or placebo was given on 2 separate study days. Three hours after drug administration, a first-degree burn injury was produced on the medial aspect of the nondominant calf (12.5 cm2, 47°C for 7 minutes). Quantitative sensory testing (QST) included pain ratings to thermal and mechanical stimuli (visual analog scale [VAS]), assessments of thermal and mechanical detection thresholds, and areas of secondary hyperalgesia. Side effects drowsiness and postural instability were assessed by subjective ratings (VAS). Results: The burn injury induced significant primary and secondary hyperalgesia (P < .0001). Gabapentin diminished the decrease in mechanical pain threshold in the burn area (P = .04) and reduced secondary hyperalgesia, but the reduction was not significant (P = .06). Heat pain thresholds, pain during the burn, and mechanical pain in the area of secondary hyperalgesia were not significantly changed by gabapentin (P < .2). Ratings of drowsiness and unsteadiness during walking were significantly higher for gabapentin than for placebo (P < .05). Conclusions: The study indicates that gabapentin has no analgesic effect in normal skin, but may reduce primary mechanical allodynia in acute inflammation following a thermal injury. These observations suggest a clinical potential of gabapentin in the treatment of postoperative pain. Reg Anesth Pain Med 2001;26:322-328.

Effect of pre- or post-traumatically applied i.v. lidocaine on primary and secondary hyperalgesia after experimental heat trauma in humans

Hyperalgesia on intradermal capsaicin application can be attenuated by systemic application of local anesthetics. We tested whether low doses of local anesthetics applied pre- or post-traumatically can reduce heat trauma-induced primary and secondary hyperalgesia in humans. Six healthy volunteers consented to the randomized, double-blind, and cross-over designed study. In each subject, a first-degree burn injury was induced three times (corresponding to a pre-traumatic, post-traumatic and control group) at an interval of at least 3 weeks. Heat was applied by a computer-controlled Peltier thermode (47°C, 5 min). In the pre-traumatic group, lidocaine infusion was commenced 30 min prior to heat trauma, and in the post-traumatic group immediately after heat trauma for a total infusion time of 60 min each. Volunteers rated pain on a visual analogue scale (VAS) between threshold and tolerance maximum (0–100% VAS). Primary hyperalgesia was quantified by determining mechanical (von Frey hairs) and thermal (Peltier thermode) pain thresholds. Secondary hyperalgesia was quantified by determining the area in which normally unpleasant von Frey hairs evoked pain or tenderness. Baseline thermal and mechanical pain thresholds did not differ between groups. Heat application always resulted in a first-degree burn injury including both primary and secondary hyperalgesia. The former remained by and large stable for about 4 h whereas the latter continuously increased within the first 2 h. Lidocaine did not affect primary hyperalgesia, irrespective of pre- or post-traumatic application, but substantially reduced the development of secondary hyperalgesia on pre-traumatic, and for tendency on post-traumatic infusion (treatment groups did not differ significantly). Burn injury-induced erythema was smallest in the pre-traumatic group and largest in the control group; however, the level of significance was not reached. Plasma concentrations of lidocaine were always higher than 1.5 μg/ml 30 min after bolus application of lidocaine and reached a peak of 2–3 μg/ml after about 1 h. Thus, local anesthetics at concentrations that do not block nerve conduction substantially affect ongoing central changes in pain processing that are induced by a real tissue trauma. A significant preemptive effect could not be demonstrated. The anti-hyperalgesic effect of lidocaine is likely based on action of central (spinal) sites, but peripheral sites may also be addressed.

Effects of local and systemic ibuprofen on primary and secondary hyperalgesia in man

Effects of topical (10 patients) and systemic (20 patients) ibuprofen on primary and secondary hyperalgesia were investigated in healthy volunteers. Hyperalgesia was produced by a local first-degree burn injury covering 12.5 cm 2 on the medial side of the calf. The studies were placebo controlled, randomized, and of crossover design. Primary hyperalgesia was quantitated by determination of heat-pain thresholds within the site of injury. Secondary hyperalgesia, outside the injury, was quantitated by determination of the area in which a mechanical punctuate stimulus elicited pain sensation. Neither topical (approximately 3 g) nor systemic ibuprofen (600 mg orally) altered primary or secondary hyperalgesia.

Photoradiation therapy of gynecologic malignancies

Four patients with gynecologic tumors recurrent either to the vagina or skin were treated with photoradiation therapy. A cytotoxic effect on the tumor was achieved by injecting hematoporphyrin derivative intravenously followed by exposing the treatment area to light of 630 nm from an argon-ion pumped-dye laser 72 hr later. Of seven tumor sites which were treated, one was completely destroyed, two were diminished in volume by more than 30%, and no response was seen in four. Toxicity was limited to one episode of facial edema and first-degree burn after prolonged exposure to bright artificial light. Phototherapy might be a useful treatment of some gynecologic tumors which recur after standard attempts at control of disease.

Care and Treatment of Burns

Pathology.--Burns are classified by their degree of severity. In the first degree, erythema or local congestion of the skin occurs and is dangerous only if extensive areas are involved. In the second degree, vesication occurs, that is, the epidermis is raised in blisters, and danger to life is as in the first degree. In the third degree there is destruction of the epidermis with raw dermis and naked nerve papillae are exposed. This is the most painful form of burn. However, healing is rapid, regeneration complete, and no contraction results. The fourth degree burn causes destruction of the dermis. The nerve terminals are destroyed. In the fifth degree there is destruction of the muscles, and in the sixth degree burn there is charring to the bone or total gangrene. The last four degrees involve all the dangers of inflammatory fever and septic absorption. However, in an extensive second degree burn the prognosis may be fatal. Treatment. Treatment depends largely upon the severity or degree of injury. In a first-degree burn an application of an oil or a soothing ointment is usually all that is necessary. A second degree burn may be accompanied first by shock. The loss of circulatory fluids plus the loss of protein of the blood into the surrounding tissue causes a decrease in the fluid content of the circulating blood which results al o in a decrease of blood pressure. This, accompanied by the pain associated with burns, if not treated immediately, may be followed by death. A sedative may be given to alleviate pain before beginning further treatments. The blisters must then be opened and cut away under an aseptic technic. Wash the areaswith boric acid or green soap solution. An application of 2-5 per cent solution of tannic acid, or a gentian violet solution (the strength depending upon the doctor's orders) used as a spray over the parts affected every fifteen minutes for the first, twenty-four hours until a hard crust is formed, is at present a specific treatment. The unaffected areas may be given general care. The child is then placed in a croup tent on a sterile sheet where electric lights are arranged either in the form of a cradle or suspended overhead by a wooden bar to keep the temperature at 90 degrees Fahrenheit. The hands and feet often must be restrained. Bandage gauze or spica bandage, three inches wide, and cotton wadding strips, two inches wide, make a very good restraint. Wrap the wrists and ankles with cotton wadding, encircle the wrists and ankles with the bandage, and make a knot