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Korean J Pain Vol. 22, No. 3, 2009 대한통증학회지 2009; 22: 216-223 DOI:10.3344/kjp.2009.22.3.216 원저 다양한만성통증질환에서 5% 리도카인패치의유용성연구 분당서울대학교병원, * 서울대학교병원, 강원대학교병원마취통증의학과 문지연ㆍ최종범ㆍ이평복ㆍ손혜민 * ㆍ남상건 * ㆍ김용철 * ㆍ이상철 * ㆍ이상진 An Open-Label Trial of the 5% Lidocaine Patches for the Treatment of Chronic Pain Jee Youn Moon, M.D., Jong Bum Choi, M.D., Pyung Bok Lee, M.D., Ph.D., He Min Son, M.D.*, Francis Sanhgun Nam, M.D.*, Young Chul Kim, M.D., Ph.D.*, Sang Chul Lee, M.D., Ph.D.*, and Sang Jin Lee, M.D. Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam, *Seoul National University Hospital, Seoul, Kangwon National University Hospital, Chuncheon, Korea Background: There have been limited reports on the effectiveness of 5% lidocaine patches (L5Ps) for treating a few types of chronic pain. We utilized L5Ps for chronic pain patients with various diagnoses and who had incompletely responded to their current treatment regimen. This study aimed at describing the results of a retrospective review of an open-label L5P trial to assess L5Ps effectiveness and safety for treating various chronic pain patients. Methods: The chronic pain patients with pain lasting longer than 6-month duration were offered a 2-week L5P treatment trial. The patients were maintained on their other analgesic regimens. The treatment effect was measured according to the change from the baseline visual analog scale (VAS) to the week 2 VAS. After a 2-week trial, the patients were asked if they perceived pain improvement with L5Ps by using a four-item Pain Relief Scale (1 = a lot of relief, 2 = slight relief, 3 = no change, 4 = worse pain). Results: In the combined patient population (n = 177), 2-week treatment with the L5Ps significantly improved the week 2 VAS (P = 0.000). Significant improvement in the VAS was reported by the chronic pain patients with postherpetic neuralgia, intercostal neuralgia, degenerative osteoarthritis at knee joint, and other maladies. A higher proportion of the chronic pain patients reported improving their pain by the L5Ps. Seven patients experienced mild or moderate patch-related adverse events. Conclusions: The L5P provided clinically meaningful pain relief in some refractory chronic pain patients without any severe adverse events. (Korean J Pain 2009; 22: 216-223) Key Words: chronic pain, intercostal neuralgia, osteoarthritis, pain scale, postherpetic neuralgia, 5% lidocaine patch. 서 만성통증은 3 개월이상지속하는국소적혹은전신적 론 인통증으로전체인구의약 15% (2 40) 가경험하는것으로알려졌으며 [1] 환자들이통증치료실을찾는주요원인중의하나이다. 만성통증은암성질환, 근골격계질환및신경병성질환등다양한원인에의해발생할수 접수일 :2009 년 7 월 6 일, 1 차수정일 : 2009 년 7 월 23 일승인일 :2009 년 8 월 3 일책임저자 : 이평복, (463-707) 경기도성남시분당구구미로 166 분당서울대학교병원마취통증의학과 Tel: 031-787-7499, Fax: 031-787-4063 E-mail: painfree@snubh.org Received July 6, 2009, Revised July 23, 2009 Accepted August 3, 2009 Correspondence to: Pyung Bok Lee Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, 166, Gumi-ro, Bundang-gu, Seongnam 463-707, Korea Tel: +82-31-787-7499, Fax: +82-31-787-4063 E-mail: painfree@snubh.org

문지연외 7 인 : The Effectiveness of 5% Lidocaine Patches 217 있는데대상포진후신경통처럼복잡한병태생리기전이작용하는경우한가지약물로만치료하기보다는항경련제, 항우울제, 아편양제제, NMDA 수용체길항제등여러약물의복합치료가필요하다. 환자에게여러약제를동시투여할때각기다른약물작용을통해치료에대한부가효과및상승효과를얻을수있지만, 약물의전신영향으로말미암은부작용및환자개인이복용하는다른질병치료제와반응하여심각한부작용을가져올수있다. 이러면통증부위에만국소적으로작용하는부위약제를환자에게적용하여약물의전신작용에의한부작용을줄이고효과적인통증감소를유도할수있다. 5% 리도카인패치 (Lidoderm R, Endo Pharmaceuticals Inc., Chadds Ford, PA, USA, 리도덤 ) 는 700 mg의리도카인이함유된 10 14 cm 2 의수용성겔을통증부위에직접부착하도록한국소제제로말초통각수용기에서비정상소디움채널의흥분을차단하여통증감작에필요한이소성임펄스의발생과과다흥분을줄여줌으로써국소진통효과를나타낸다고생각한다 [2]. 리도덤을부착할때전신으로흡수되는리도카인은 12 시간동안전체용량의 3% 정도에불과하고인체내축적효과가없고용량조절이필요없어임상에서편리하게사용할수있으며환자순응도가높다는장점을지닌다 [3]. 1999년미국식약청 (US Food and Drug Administration [FDA]) 에서리도덤을대상포진후신경통치료제로승인하였고 [4] 후에시행된대규모임상실험을통해대상포진후신경통환자에서단기간그리고장기간리도덤부착시신경병성통증완화효과가있음이입증된바있다 [5,6]. 또한, 리도덤이당뇨병성신경통증 [7,8], 요부통증 [8,9], 수술후절개부위통증 [10], 근근막통증증후군 [11], 퇴행성슬관절염 [12] 등에도효과가있다는증례보고들이계속발표되고있다. 그러나우리나라의경우대상포진후신경통환자의 1차약물치료제로리도덤을소개하고있지만 [13] 대상포진후신경통환자들을대상으로한임상연구는극히드물거나대상환자수가 15명정도의시험적인연구에불과하고 [14] 그외질병에대한리도덤의통증완화효과를연구한보고는아직전혀없는실정이다. 따라서기존연구결과에근거하여 6개월이상지속하는만성통증을지니고있고 3개월이상고전적인경구약물치료와주사치료를시행하였음에도불구하고통증을지속적으로호소하는만성통증환자들에게리도덤을 2주이상처방하였다. 이환자들을대상으로의무기록을후향적으로검토하여리도덤치료효과에대한 결과를분석하고자한다. 대상및방법 1. 연구대상병원윤리위원회의사전심사를거친뒤연구를진행하였고 2008년 7월부터 2009년 6월까지통증치료실을방문한환자중리도덤을처방한환자들을대상으로하였다. 6개월이상같은부위에지속적인통증을호소하며통각과민성통증지점또는통증유발점이있고통증치료실방문뒤 3개월이상고전적인약물치료와주사치료를시행하였음에도불구하고통증이같은강도로지속된환자에게리도덤을처방하였다. 또한, 부분적인통증의호전을보이지만시각아날로그척도 (visual analogue scale, VAS) 가 4 이상으로만족할만한결과를얻지못한환자들도함께포함하였다. 패치부착부위에염증성병변이있는경우, 패치제제에접촉성알레르기가있거나아마이드형국소마취제에알레르기가있는경우, 리도덤을처방한 2주동안경막외스테로이드및국소마취제등을주입하거나통증유발점에국소마취제를주사한경우, 최근 3개월내환부에보툴리눔독소를주입받은경우, 다른리도카인제제를사용하고있거나제1형항부정맥제제를복용하는환자들은연구에서제외하였다. 2. 리도덤적용및효과평가패치를처방하는첫날통증위치를확인하고리도덤을 2주간하루에 1회, 12시간동안환부크기에따라 1장에서 2장까지부착하도록하였고패치를부착하는 2주동안기존에지속해오던 NSAIDs, COX-2 inhibitor, acetaminophen, gabapentin, pregabalin, antidepressant, SSRI (selective serotonin receptor inhibitor), opioid analgesics와같은경구약물의종류및용량을동일하게유지하였다. 리도덤의안정성및환자순응도를평가하기위해환자의활력징후, 이학적검사, 임상검사 ( 혈액검사, 생화학검사, 요검사 ), 리도덤에의한부작용, 다른약제복용과연관된부작용, 리도덤부착으로말미암은환자의불편감등을조사하였다. 이연구는어떤종류의만성통증군에서리도덤부착시증상의개선을보이며패치의사용을지속해야하는지를알고자하는것이므로, 평가의지표로패치처방전의 VAS (baseline VAS) 와처방 2주후의 VAS (week 2 VAS) 기록을사용했으며, 효과판정을위해환자에게

218 JY Moon, et al / Korean J Pain Vol. 22, No. 3, 2009 리도덤에의한통증완화정도를 1: 통증이크게완화된다, 2: 통증이약간완화된다, 3: 통증이완화되지않지만, 통증을악화시키지는않는다, 4: 통증이오히려악화된다중하나에표시하게하였다. 3. 통계분석 치료실험후후향적방법으로임상적변수에대한통계분석을시행하였다. 한개체에서리도덤부착전후의 VAS에차이가있는지를알아보기위해 paired t-test를실시한뒤각진단명에따라 paired t-test와 Wilcoxon Signed Rank Test를실시하였다. 성별에의한차이를알아보기위해 Mann-Whitney test를실시하고각변수간의상관관계는 Pearson s correlation과 Spearman s correlation을이용해알아보았다. 통계프로그램은 SPSS for windows ver. 15.0을사용하였으며모든결과는평균 ± 표준편차로나타내었고 P value가 0.05보다작은경우를통계적으로유의한것으로간주하였다. Table 1. Demographic Data Number of patient (M/F) 177 (71/106) Age (yr) 60.3 ± 19.9 Duration of symptom (months) 26.0 ± 28.7 Diagnosis 결 이기간동안리도덤을처방받은환자는총 218명이었고이들중 177명을대상으로연구가진행되었다. 이중남자가 71명, 여자가 106명이었으며성별에따른측정값의차이는존재하지않았다. 평균연령은 60.3 ± 19.9세 Number of patient (M/F) Postherpetic neuralgia 101 (41/60) Intercostal neuralgia 15 (6/9) CRPS type 1 15 (9/6) Degenerative OA at knee joint 14 (4/10) Low back pain 14 (6/8) Diabetic neuropathy 4 (1/3) Myofascial pain syndrome 4 (1/3) Rib fracture 3 (1/2) Plantar fascitis 3 (1/2) Carpal tunnel syndrome 1 (0/1) Lateral epicondylitis 1 (1/0) Ankle instability 1 (0/1) Morton s neuroma 1 (0/1) Values are number of patients or mean ± SD. CRPS: complex regional pain syndrome, OA: osteoarthritis. 과 로, 평균이환기간은 26.0 ± 28.7개월이었다. 각질병별로환자분포를살펴본결과대상포진후신경통 101명, 늑간신경통 15명, 복합부위통증증후군제1형 15명, 슬관절의중등도이상의퇴행성골관절염 14명, 하부요통 14명, 근근막통증증후군과당뇨병성말초신경병증이각각 4명, 늑골골절, 족저근막염이각각 3명, 그외수근관증후군, 외측상과염, 족관절불안정성, Morton 신경종이각각 1명씩이었다 (Table 1). 리도덤처방전후의활력징후, 이학적검사, 임상검사 ( 혈액검사, 생화학검사, 요검사 ), 리도덤에의한부작용, 다른약제복용과연관된부작용등을조사한결과 2명이리도덤부착부위의발진및피부자극으로도중탈락하였고그외환자에서리도덤부착부위에조이는듯한이상감각 (1명), 부착부위의경미한발진 (2명), 부착부위의가려움증 (2명) 을호소하였으나활력징후의변화나이학적검사의변화, 임상검사변화및기존복용약제와연관된부작용을호소하는경우는없었다 (Table 2). 환자수가 10명을넘는상위 5개질병군에대하여리도덤처방전과후의 VAS 측정치를분석하였다. 그결과대상포진후신경통 (P = 0.000), 늑간신경통 (P = 0.001), 슬관절퇴행성관절염 (P = 0.01) 환자군에서통계적으로유의한차이를보였고복합부위통증증후군제1형 (P = 0.125) 과하부요통 (P = 1.00) 에서는통계적으로유의하지않은것으로나타났다 (Table 3, Fig. 1). 그리고각변수간의상관관계를살펴보면대상포진후신경통환자군에서환자의나이와리도덤처방전후 VAS 변화값사이에피어슨 r이 0.219 (P = 0.031) 로유의한일치성이있음이발견되었다 (Fig. 2). 리도덤의통증개선정도에대한평가를환자에게실 Table 2. Number of Patients with Lidoderm-related Adverse Events Adverse event n Severity Application site irritation 2 1 1 Application site rash 2 1 1 Application site paresthesia 1 1 Application site pruritus 2 2 Mild Moderate Severe During 2 weeks of treatment with the lidocaine 5% patch, 2 patients (1.1%) developed moderate irritation and rash at the application site and 4 patients (2.3%) developed tolerable adverse events.

문지연외 7 인 : The Effectiveness of 5% Lidocaine Patches 219 Table 3. Mean Changes in VAS from Baseline to Week 2 in Each Patient Group Baseline VAS Week 2 VAS Total patients 6.5 ± 1.9 (n = 135) 5.0 ± 2.5* (n = 135) Postherpetic neuralgia 6.0 ± 2.0 (n = 73) 4.6 ± 2.5* (n = 73) Intercostal neuralgia 6.5 ± 1.6 (n = 11) 4.2 ± 0.9* (n = 11) CRPS type 1 8.4 ± 1.0 (n = 11) 7.9 ± 1.0 (n = 11) Degenerative OA at knee joint 7.5 ± 1.7 (n = 13) 4.3 ± 1.3* (n = 13) Low back pain 7.1 ± 2.1 (n = 11) 7.3 ± 1.5 (n = 11) Values are mean ± SD. VAS: visual analog scale, n: number of patient, CRPS: complex regional pain syndrome, OA: osteoarthritis. *P 0.01 relative to baseline. Fig. 2. The relation between age of patients of postherpetic neuralgia and difference of week 2 VAS from baseline VAS with Pearson s correlation coefficient There is positive correlation between age of patients with postherpetic neuralgia and difference of Week 2 VAS from baseline VAS (r = 0.219, P = 0.031). VAS: visual analog scale. Fig. 1. Mean changes in VAS from baseline to week 2 in each patients group. *P 0.01, baseline vs Week 2 VAS. Error bars represent one standard deviation. VAS: visual analog scale, PHN: postherpetic neuralgia, ICN: intercostals neuralgia, CRPS: complex regional pain syndrome, OA: osteoarthritis, LBP: low back pain. 시한결과응답한환자중대상포진후신경통환자군에서 1: 통증이크게완화된다 24명 (40%), 2: 통증이약간완화된다 21명 (35%), 3: 통증이완화되지않지만, 통증을악화시키지는않는다 15명 (25%), 4: 통증이오히려악화된다 0명 (0%) 으로전체환자의과반수이상 (75%) 에서리도덤이대상포진후신경통완화에효과가있다고하였다. 늑간신경통의경우 1: 통증이크게완화된다 5명 (38.5%), 2: 통증이약간완화된다 3명 (23.1%) 으로역시응답한환자의과반수 (61.5%) 에서리도덤치료효과가있다고답하였다. 또한, 슬관절의퇴행성관절염환자군의경우응답한 14명의환자가운데 64.3% 인 9명의환자가 1: 통증이크게완화된다고하였고 4명 (28.6%) 이 2: 통증이약간완화된다고대답하여거의모든환자가리도덤치료가통증완화에효과적이라고답하였다. 반면 Fig. 3. Proportion of patients by four-item Pain Relief Scale after a 2-week patch use. PHN: postherpetic neuralgia, ICN: intercostals neuralgia, CRPS: complex regional pain syndrome, OA: osteoarthritis, LBP: low back pain. 하부요통과복합부위통증증후군제1형환자는과반수이하 ( 각각 46.2%, 41.7%) 에서통증완화에효과가있다고하였으나 4: 통증이악화된다라고대답한환자는없었다 (Fig. 3). 그외질병에서리도덤의통증개선정도에대한평가는 Table 4에제시하였다 (Table 4).

220 JY Moon, et al / Korean J Pain Vol. 22, No. 3, 2009 Table 4. Report of Pain Relief by the Topical Lidocaine Patch (Lidoderm) Diagnosis (n) n (%) 1 2 3 4 Missing Postherpetic neuralgia (n = 101) 24 (40%) 21 (35%) 15 (25%) 46 Intercostal neuralgia (n = 15) 5 (38.5%) 3 (23.1%) 5 (38.5%) 2 CRPS type 1 (n = 15) 2 (15.4%) 3 (20%) 8 (61.5%) 2 Degenerative OA at knee joint (n = 14) 9 (64.3%) 4 (28.6%) 1 (7.1%) Low back pain (n = 14) 1 (7.7%) 5 (38.5%) 7 (53.8%) 1 Diabetic neuropathy (n = 4) 2 2 Myofascial pain syndrome (n = 4) 2 2 Rib fracture (n = 3) 2 1 Plantar fasciitis (n = 3) 2 1 Carpal tunnel syndrome (n = 1) 1 Lateral epicondylitis (n = 1) 1 Ankle instability (n = 1) 1 Morton s neuroma (n = 1) 1 After 2-week patch use, patients were asked about degree of pain relief which was rated using a verbal four-item Pain Relief Scale (1: a lot of relief, 2: slight relief, 3: no relief, 4: worse pain). CRPS: complex regional pain syndrome, OA: osteoarthritis. 고찰이번연구에서 2주동안리도덤을부착한 177명의환자들을대상으로리도덤부착전후의 VAS를비교한결과리도덤부착전 VAS보다부착후 VAS가유의하게감소함을확인할수있었다. 리도덤에의한통증완화효과를질병군별로살펴보면대상포진후신경통, 퇴행성슬관절염, 늑간신경통환자의과반수에서리도덤부착이통증완화에도움이된다고하였고하부요통과복합부위통증증후군제1형환자의경우 40% 이상에서효과가있다고하였으며늑골골절, 근근막통증증후군, 당뇨병성말초신경병증, 족저근막염환자에게서도리도덤부착이통증완화에도움이된다고답하였다. 건강한자원자를대상으로한 5% 리도카인패치의약동학과안전성에관한연구에서패치에함유된리도카인의생체이용률은약 3% 로패치 1 장을부착한경우최대혈중농도는 128 ng/ml였고이는리도카인이부정맥발생을억제하는 1,000 1,500 ng/ml의혈중농도에크게못미치는것이다 [3]. 역시건강한자원자를대상으로한번에 4장의리도카인패치를 3일연속으로 12시간마다교체하며부착한경우, 그리고 24시간마다교체하며부착한경우혈중리도카인농도가각각 154와 186 ng/ml로일정하게유지되었다고하였고 [15] 이는패치 1 장을부착한경우나타날수있는 130 ng/ml와유사한수준이었다. 또한, 이들중일부에게패치부착부위에 치료를요하지않는경미한피부반응이나타났으나대부분은부작용을가져오지않았고 24시간동안지속적으로부착하였음에도 pinprick, light touch와같은피부감각이유지되었다고보고하였다. 이번연구에서도부착부위의자극증상으로 2명의환자가리도덤부착을도중에중단하였으나대다수의환자에게심한약제관련부작용이나다른전신작용약물과의부작용은나타나지않았다. 따라서이번연구를통해 5% 리도카인패치에통증완화효과를보인질병군의환자들이기존 1 차사용약제에일부의통증완화만을나타내는경우리도카인패치를함께처방하는것은만성통증으로고통받는환자들에게상당히안전하고효과적인통증완화를제공할가능성을넓히고삶의질을높이는방법이라생각된다. Dever와 Galer는 [16] 5% 리도카인패치를다양한만성신경병성통증에적용하려고시도하였다. 그들은 6명의복합부위통증증후군환자를포함한 16명의다양한신경병성통증환자들에게 5% 리도카인패치를 1회적용후통증에대한반응을 6개의항목으로구성된통증완화평가로표시하게하였다. 그결과복합부위통증증후군환자 (6명) 와대퇴신경지각이상증환자 (2명), 늑간신경통환자 (1명) 모두에서중등도이상의통증호전을나타냈고수술후절개부위통증및그부위에생긴신경종에패치를부착한환자 (5명) 모두에서도경도이상의통증호전을확인할수있었다. 이번연구에서늑간신경통환자는리도덤처방전후의 VAS가유의하게감소하였지

문지연외 7 인 : The Effectiveness of 5% Lidocaine Patches 221 만 (P = 0.001) 복합부위통증증후군환자는 Dever의연구결과와달리유의한감소를하지않았는데 (P = 0.125) 그이유중의하나로 Fishbain 등은 [17] 보상및소송과같은변수를제시하였다. 이번연구에포함된 15명의복합부위통증증후군환자중 10명이보상및소송에직간접적으로연관되어있었지만, 통증개선기여도응답결과와유의한상관관계를나타내지는않았다 (r = 0.548, P = 0.065). 또한, Fishbain 등은 114명의만성통증환자들을대상으로 5% 리도카인패치를처방한결과 87명 (76.3%) 에서효과가있다고하였고 27명 (23.7%) 에서효과가없다고하였는데효과가없다고예상할수있는여러요인가운데통증위치중하요부, 척추주변근육에통증이있는경우, 척추관협착증으로진단받거나신경병성통증이아닌경우등을들었고통계적으로유의하게통증개선효과를나타내는예측할수있는 3가지요인으로첫째, 통증이수면장애를유발하는경우, 둘째, 하요부가아닌부위의통증, 특히무릎이나수술후상처부위인경우, 셋째, 소송과연관되어있지않은경우를들었다. 이전증례나 pilot 연구에서하부요통에 5% 리도카인패치가효과적이라는보고가종종있었고 [9,18] Galer 등은 71명의급성, 아급성, 만성요통환자들을대상으로 5% 리도카인을부착하도록한뒤 2주, 6주후측정한 NPS (Neuropathic Pain Scale) 에서유의한 (P = 0.001) 통증완화효과를나타내었다고하였다 [19]. 그러나이번연구결과에서하부요통환자의리도덤에의한통증완화효과는유의하지않았고 (P = 1.00) 하부요통환자에게실시한리도덤의통증완화평가역시과반수의환자에서 3: 통증이완화되지않지만, 통증을악화시키지는않는다고답하여 David 등의연구에가까운결과를나타내었다. 그이유로이번연구에서는 NPS가아니라단순히 VAS로치료효과를평가했기때문에평가기준이달랐다는것, 요통의매우복잡한병태생리등을들수있겠지만, 하부요통환자에서 5% 리도카인의통증개선효과는아직논쟁의여지가많이있으며더대단위의체계적인무작위위약대조시험이필요할것으로생각한다. 한편, 퇴행성슬관절염환자에서리도덤의통증개선효과가뛰어나다는이번연구결과는 5% 리도카인패치부착시통증개선효과를예측할수있는부위로서슬관절을꼽은 [17] Fishbain의연구결과와일치하였으며퇴행성슬관절염발병의병태생리적원인으로일반적으로알려진만성염증반응외에도소디움통로의과발현및상향조절이연관될수있음을 [20] 강력히시사하고있다. 그리고 Galer 등은 [21] 5% 리도카인패치의슬관 절부착으로퇴행성슬관절염의통증개선뿐만아니라육체적활동개선, 관절강직개선등의효과도함께있다고하였고, 최근발표된논문에의하면퇴행성슬관절염환자에서 5% 리도카인패치가 celecoxib와비교하여현저하게낮은부작용발생률을나타내지만진통효과는동일하다고하여 [12] 퇴행성슬관절염환자의치료제로서큰가능성을나타내었다. 대상포진후신경통환자들을대상으로한이전연구를살펴보면 White 등은 [22] gabapentin에만족할만한통증완화를얻지못한대상포진후신경통, 당뇨병성말초신경통, 하부요통환자들을대상으로기존약제를지속투약하면서 2주간 5% 리도카인패치를통증부위에부착하도록하였다. 그결과큰부작용없이환자들의통증강도가매우감소하고삶의질이향상하였다고발표하였다. 특히만성통증환자에서여러약물을조합하여사용해야하는경우국소적으로효과를나타내고전신흡수가적은 5% 리도카인패치야말로약물의전신부작용및약제간상호부작용을일으키지않는이상적인치료제라고주장하였다. 이후 Baron 등은 [23] 75명의대상포진후신경통환자와 71명의당뇨병성말초신경통환자를두그룹으로나누어한그룹에는 pregabalin을, 다른그룹에는 5% 리도카인패치를 4주동안적용한결과두그룹에서모두통계적으로의미있는통증경감을얻었다고하였다. 특히약제와연관된부작용은 5% 리도카인패치를부착한경우 3.9%, pregabalin 투여환자에서 39.2% 였으며이로인해연구에서도중탈락한환자수는패치부착그룹이 1.3%, pregabalin 투여그룹이 20.3% 였다. 이번연구에서도대상포진후신경통환자의리도덤적용전후의 VAS를비교한결과는 P 값이 0.000이었고 75% 의환자에서리도덤이통증완화에효과적이라고하여기존연구와유사한결과를얻을수있었다. 이와같은연구결과들을토대로발표된근거중심의치료지침에서국소부위의신경병성통증을치료하기위한첫번째선택약제로기존의 gabapentin, pregabalin과함께 5% 리도카인패치가추천되고있으며 [24,25] 특히고령화시대를맞아연령증가에따른발병률이급격하게증가하는대상포진후신경통환자에서중추신경계작용약물로인한어지럼증, 졸림, 보행장애와다른약제와의상호작용으로인한부작용을일으키지않는 5% 리도카인패치는매우이상적인치료제임이확실하다. 이번연구에서 5% 리도카인패치인리도덤을다양한만성통증환자에게 2주동안부착하여어느질병군에서통증완화효과를얻을수있는지에관하여조사해보았

222 JY Moon, et al / Korean J Pain Vol. 22, No. 3, 2009 다. 물론대상포진후신경통환자군을제외한다른질병군의환자수가 15명이하로소수라는것과무작위위약대조군실험이아니라는것, 리도덤의통증완화효과를단순히 VAS로평가하였다는점, 보다장기간투약관찰한결과를제시하지못한점등을이연구의한계로볼수있다. 그러나이번연구를통해리도덤으로부터이익을얻을수있는만성통증환자군을예측하고앞으로이들에게부작용발생률이낮은치료방법을함께제공하여빠른통증완화효과를얻도록할수있으리라기대된다. 이번연구에서긍정적인반응을나타낸질병군에대해보다체계적인대단위무작위대조군실험이뒤따라야하겠다. 참고문헌 1. Verhaak PF, Kerssens JJ, Dekker J, Sorbi MJ, Bensing JM: Prevalence of chronic benign pain disorder among adults: a review of the literature. Pain 1998; 77: 231-9. 2. Mao J, Chen LL: Systemic lidocaine for neuropathic pain relief. Pain 2000; 87: 7-17. 3. Campbell BJ, Rowbotham M, Davies PS, Jacob P 3rd, Benowitz NL: Systemic absorption of topical lidocaine in normal volunteers, patients with post-herpetic neuralgia, and patients with acute herpes zoster. J Pharm Sci 2002; 91: 1343-50. 4. Davies PS, Galer BS: Review of lidocaine patch 5% studies in the treatment of postherpetic neuralgia. Drugs 2004; 64: 937-47. 5. Baron R, Mayoral V, Leijon G, Binder A, Steigerwald I, Serpell M: Efficacy and safety of 5% lidocaine (lignocaine) medicated plaster in comparison with pregabalin in patients with postherpetic neuralgia and diabetic polyneuropathy: interim analysis from an open-label, two-stage adaptive, randomized, controlled trial. Clin Drug Investig 2009; 29: 231-41. 6. Zin CS, Nissen LM, Smith MT, O'Callaghan JP, Moore BJ: An update on the pharmacological management of post-herpetic neuralgia and painful diabetic neuropathy. CNS Drugs 2008; 22: 417-42. 7. Barbano RL, Herrmann DN, Hart-Gouleau S, Pennella- Vaughan J, Lodewick PA, Dworkin RH: Effectiveness, tolerability, and impact on quality of life of the 5% lidocaine patch in diabetic polyneuropathy. Arch Neurol 2004; 61: 914-8. 8. Argoff CE, Galer BS, Jensen MP, Oleka N, Gammaitoni AR: Effectiveness of the lidocaine patch 5% on pain qualities in three chronic pain states: assessment with the neuropathic pain scale. Curr Med Res Opin 2004; 20(Suppl 2): 21-8. 9. Hines R, Keaney D, Moskowitz MH, Prakken S: Use of lidocaine patch 5% for chronic low back pain: a report of four cases. Pain Med 2002; 3: 361-5. 10. Saber AA, Elgamal MH, Rao AJ, Itawi EA, Martinez RL: Early experience with lidocaine patch for postoperative pain control after laparoscopic ventral hernia repair. Int J Surg 2009; 7: 36-8. 11. Affaitati G, Fabrizio A, Savini A, Lerza R, Tafuri E, Costantini R, et al: A randomized, controlled study comparing a lidocaine patch, a placebo patch, and anesthetic injection for treatment of trigger points in patients with myofascial pain syndrome: evaluation of pain and somatic pain thresholds. Clin Ther 2009; 31: 705-20. 12. Kivitz A, Fairfax M, Sheldon EA, Xiang Q, Jones BA, Gammaitoni AR, et al: Comparison of the effectiveness and tolerability of lidocaine patch 5% versus celecoxib for osteoarthritis-related knee pain: post hoc analysis of a 12 week, prospective, randomized, active-controlled, open-label, parallel-group trial in adults. Clin Ther 2008; 30: 2366-77. 13. Sim WS, Choi JH, Han KR, Kim YC: Treatment of herpes zoster and postherpetic neuralgia. Korean J Pain 2008; 21: 93-105. 14. Kim TH, Choi PT, Yoo JH, Kim KJ: A study on the effect of topical 5% lidocaine patches on postherpetic neuralgia. Annals of Dermatology 2007; 19: 1-8. 15. Gammaitoni AR, Alvarez NA, Galer BS: Pharmacokinetics and safety of continuously applied lidocaine patches 5%. Am J Health Syst Pharm 2002; 59: 2215-20. 16. Devers A, Galer BS: Topical lidocaine patch relieves a variety of neuropathic pain conditions: an open-label study. Clin J Pain 2000; 16: 205-8. 17. Fishbain DA, Lewis JE, Cole B, Cutler B, Rosomoff HL, Rosomoff RS: Lidocaine 5% patch: an open-label naturalistic chronic pain treatment trial and prediction of response. Pain Med 2006; 7: 135-42. 18. Gimbel J, Linn R, Hale M, Nicholson B: Lidocaine patch treatment in patients with low back pain: results of an open-label, nonrandomized pilot study. Am J Ther 2005; 12: 311-9. 19. Galer BS, Gammaitoni AR, Oleka N, Jensen MP, Argoff CE: Use of the lidocaine patch 5% in reducing intensity of various pain qualities reported by patients with low-back pain. Curr Med Res Opin 2004; 20(Suppl 2): 5-12. 20. Zhang JM, Li H, Munir MA: Decreasing sympathetic sprouting in pathologic sensory ganglia: a new mechanism for treating neuropathic pain using lidocaine. Pain 2004; 109: 143-9. 21. Galer BS, Sheldon E, Patel N, Codding C, Burch F, Gammaitoni AR: Topical lidocaine patch 5% may target a novel underlying pain mechanism in osteoarthritis. Curr Med Res Opin 2004; 20: 1455-8. 22. White WT, Patel N, Drass M, Nalamachu S: Lidocaine patch 5% with systemic analgesics such as gabapentin: a rational polypharmacy approach for the treatment of chronic pain. Pain Med 2003; 4: 321-30.

문지연외 7 인 : The Effectiveness of 5% Lidocaine Patches 223 23. Baron R, Mayoral V, Leijon G, Binder A, Steigerwald I, Serpell M: Efficacy and safety of combination therapy with 5% lidocaine medicated plaster and pregabalin in postherpetic neuralgia and diabetic polyneuropathy. Curr Med Res Opin 2009; 25: 1677-87. 24. Dworkin RH, O'Connor AB, Backonja M, Farrar JT, Finnerup NB, Jensen TS, et al: Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain 2007; 132: 237-51. 25. Finnerup NB, Otto M, Jensen TS, Sindrup SH: An evidence- based algorithm for the treatment of neuropathic pain. MedGenMed 2007; 9: 36.