Lynch M E, Clark A J, Sawynok J
Pain Management Unit, Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, Nova Scotia.
Clin J Pain. 2003 Sep-Oct;19(5):323-8. doi: 10.1097/00002508-200309000-00007.
The involvement of ongoing peripheral activity in the generation of nociceptive input in neuropathic pain suggests that topical drug delivery may be useful as a treatment strategy. This is a pilot study providing initial information regarding the use of novel topical preparations containing amitriptyline (AMI), ketamine (KET), and a combination of both in the treatment of neuropathic pain.
The study design included a 2 day randomized, double blind, placebo controlled, 4 way cross-over trial of all treatments, followed by an open label treatment phase using the combination cream for 7 days. Twenty volunteers with chronic neuropathic pain were randomly assigned to treatment order and applied 5 mls of each topical treatment (1% AMI, 0.5% KET, combination AMI 1%/KET 0.5%, and placebo) for 2 days. Measures of pain at the end of each block included the short form McGill Pain Questionnaire (MPQ) and visual analog scales (VAS) for present pain intensity and pain relief. Eleven subjects who judged subjective improvement from any treatment in the initial trial entered the open-label trial and used the combination cream for 7 days. Pain levels were recorded daily using the same measures. Blood levels for amitriptyline and ketamine were performed at 7 days to determine whether systemic absorption had occurred.
There was no statistically significant difference from placebo after 2 days for any treatment during the double blind component of the trial. In the 11 subjects who used the combination cream, there was a statistically significant effect, with subjects reporting significantly greater analgesia by days 3 to 7 according to measures of pain and pain relief. Blood levels revealed that there was no significant systemic absorption of amitriptyline or ketamine. Only 2 subjects experienced side effects; these were minor and did not lead to discontinuation of the cream.
This pilot study demonstrated a lack of effect for all treatments in the 2 day double blind placebo controlled trial, followed by analgesia in an open label trial in a subgroup of subjects who chose to use the combination cream for 7 days. Blood analysis revealed no significant systemic absorption of either agent after 7 days of treatment, and creams were well tolerated. A larger scale randomized trial over a longer interval is warranted to examine further effects observed in the open label trial.
持续性外周活动参与神经病理性疼痛中伤害性输入的产生，这表明局部给药可能是一种有用的治疗策略。这是一项初步研究，提供了有关使用含阿米替林（AMI）、氯胺酮（KET）以及两者组合的新型局部制剂治疗神经病理性疼痛的初始信息。
研究设计包括为期2天的所有治疗的随机、双盲、安慰剂对照、四臂交叉试验，随后是使用复方乳膏进行7天的开放标签治疗阶段。20名患有慢性神经病理性疼痛的志愿者被随机分配治疗顺序，每种局部治疗（1% AMI、0.5% KET、1% AMI/0.5% KET复方制剂和安慰剂）涂抹5毫升，持续2天。每个治疗阶段结束时的疼痛测量包括简式麦吉尔疼痛问卷（MPQ）以及当前疼痛强度和疼痛缓解的视觉模拟量表（VAS）。在初始试验中判断从任何治疗中主观症状改善的11名受试者进入开放标签试验，并使用复方乳膏7天。每天使用相同的测量方法记录疼痛水平。在第7天检测阿米替林和氯胺酮的血药浓度，以确定是否发生全身吸收。
在试验的双盲部分，任何治疗在2天后与安慰剂相比均无统计学显著差异。在使用复方乳膏的11名受试者中，有统计学显著效果，根据疼痛和疼痛缓解测量，受试者在第3至7天报告镇痛效果显著更佳。血药浓度显示阿米替林或氯胺酮无显著全身吸收。只有2名受试者出现副作用；这些副作用轻微，未导致乳膏停用。
这项初步研究表明，在为期2天的双盲安慰剂对照试验中，所有治疗均无效，随后在选择使用复方乳膏7天的亚组受试者的开放标签试验中出现镇痛效果。血液分析显示，治疗7天后两种药物均无显著全身吸收，乳膏耐受性良好。有必要进行一项更大规模、更长时间间隔的随机试验，以进一步研究在开放标签试验中观察到的效果。
