Pedersen J L, Galle T S, Kehlet H
Department of Surgical Gastroenterology, Hvidovre University Hospital, Denmark.
Anesthesiology. 1998 Jul;89(1):58-66. doi: 10.1097/00000542-199807000-00011.
BACKGROUND. This study examined the analgesic effect of local ketamine infiltration, compared with placebo and systemic ketamine, in a human model of inflammatory pain.
Inflammatory pain was induced by a burn (at 47 degrees C for 7 min; wound size, 2.5 x 5 cm) on the calf in 15 volunteers on 3 separate days with 7-day intervals. They received either (1) subcutaneous infiltration with ketamine in the burn area (local treatment) and contralateral placebo injections, or (2) subcutaneous ketamine contralateral to the burn (systemic treatment) and placebo in the burn area, or (3) placebo on both sides. The study was double-blinded and the order of the treatments was randomized. Hyperalgesia to mechanical and heat stimuli was examined by von Frey hairs and contact thermodes (3.75 and 12.5 cm2), and pain was rated using a visual analog scale (0-100).
The burns produced significant hyperalgesia. Local ketamine infiltration reduced pain during the burn injury compared with systemic treatment and placebo (P < 0.01). Heat pain thresholds were increased by local ketamine treatment compared with placebo immediately after injection (P < 0.03), and so were the mechanical pain thresholds (P = 0.02). Secondary hyperalgesia and suprathreshold pain responses to heat and mechanical stimuli were not significantly affected by local ketamine. No difference between local ketamine and placebo could be detected 1 h and 2 h after the burn.
Ketamine infiltration had brief local analgesic effects, but several measures of pain and hyperalgesia were unaffected. Therefore, a clinically relevant effect of peripheral ketamine in acute pain seems unlikely.
背景。本研究在人类炎性疼痛模型中，比较了局部氯胺酮浸润与安慰剂及全身应用氯胺酮的镇痛效果。
在15名志愿者的小腿上通过烧伤（47摄氏度，持续7分钟；伤口大小为2.5×5厘米）诱导炎性疼痛，分3天进行，间隔7天。他们接受以下治疗之一：（1）在烧伤区域皮下浸润氯胺酮（局部治疗）并在对侧注射安慰剂，或（2）在烧伤对侧皮下注射氯胺酮（全身治疗）并在烧伤区域注射安慰剂，或（3）双侧均注射安慰剂。研究采用双盲法，治疗顺序随机。通过von Frey毛发和接触式热探头（3.75平方厘米和12.5平方厘米）检测对机械和热刺激的痛觉过敏，并用视觉模拟量表（0 - 100）对疼痛进行评分。
烧伤产生了显著的痛觉过敏。与全身治疗和安慰剂相比，局部氯胺酮浸润在烧伤损伤期间减轻了疼痛（P < 0.01）。与安慰剂相比，局部氯胺酮治疗在注射后立即提高了热痛阈值（P < 0.03），机械痛阈值也有所提高（P = 0.02）。局部氯胺酮对继发性痛觉过敏以及对热和机械刺激的阈上疼痛反应没有显著影响。烧伤后1小时和2小时，局部氯胺酮与安慰剂之间未检测到差异。
氯胺酮浸润具有短暂的局部镇痛作用，但多项疼痛和痛觉过敏指标未受影响。因此，外周应用氯胺酮在急性疼痛中产生临床相关效果的可能性似乎不大。
