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1 Oral Biology Research, 2018; June 30, 42(2):67-72 Copyright c 2018, Oral Biology Research Institute DOI: /obr Original Article ORAL BIOLOGY RESEARCH Evaluation of the treatment and prognosis of the patients with orofacial pain of unknown cause Dong-Woo Kang and Young-Kyun Kim* Department of Oral and Maxillofacial Surgery, Section of Dentistry, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea (Received Feb 12, 2018; Revised version received [1] Mar 3, 2018 [2] Apr 16, 2018; Accepted Apr 17, 2018) ABSTRACT The aim of this study was to evaluate the symptoms, diagnoses, clinical treatment and prognoses of patients with orofacial pain of unknown origin. The study included 61 patients (13 males, 48 females, mean age 60.8 years) who experienced orofacial pain of unknown etiology, except for those with definite causes including dental pain, infection, osteomyelitis, and temporomandibular joint disease. Clinical examinations included patients clinical signs, radiological examinations (radiographs, CT, MRI, bone scan), blood tests, thermography, electric pulp tests, electrophysiological examinations, and anesthesia for diagnostic purposes. The treatment methods included medication, physiotherapy, dental treatment, periodontal treatment, surgical operation, and consultation, taking into consideration the precise diagnosis and symptoms for each patient. We retrospectively reviewed the medical records and evaluated the treatment duration and prognosis for each diagnosis. There were more female patients than male patients (78.7% female) and the mean age for all participants was 60.8 years. The mean duration of treatment for orofacial pain was 32 months; the traumatic neuropathy group had the shortest duration, 29.1 months, and the trigeminal neuralgia group had the longest duration, 52.9 months. Atypical odontalgia was the most favorable prognosis, followed by psychological pain, trigeminal neuralgia, traumatic neuropathy, and atypical facial pain. In all cases of oral facial pain, a significant relief of symptoms was observed after treatment. The outcome of current medications and physical therapies for patients with unexplained orofacial pain is generally good. KEY WORDS: Clinical treatment, Orofacial pain, Prognosis 서 론 구강안면통증은만성적이면서복합적인안면부통증과구강기능장애를진단하고관리하는치의학의분야이다 [1,2]. 또한, 두개내및두개의구조물과연관된병소나장애, 신경혈관성장애, 신경병변성장애, 그리고심인성통증장애와연관되어나타나는구강안면및목부위의통증을의미한다. 구강안면부는구조와기능이매우다양하고신경의분포가조밀하고복잡하며신체및심리적인조건에따라영향을받을수있어구강안면통증이나질병이발생할경우임상증상이매우다양하고복잡한양상으로나타날수있다. 같은질병이라할지라도환자에따라 *Corresponding author: Young-Kyun Kim Department of Oral and Maxillofacial Surgery, Section of Dentistry, Seoul National University Bundang Hospital, 82 Gumi-ro 173beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do 13620, Republic of Korea Tel.: , Fax: kyk0505@snubh.org 증상이확연하게다를수도있고, 환자가통증을호소하지만신체적, 임상적으로아무런이상증상을발견할수없는경우도있어진단및치료가어려운경우가많다. Okeson에의하면구강안면통증은신체적인요소 (Axis 1) 와심리적인요소 (Axis 2) 로구분된다 [3,4]. 신체적인요인은치성통증을포함하여턱관절장애, 저작근이나경추같은근골격계장애, 구강점막질환이나침샘질환같은구강연조직의장애, 삼차신경통이나편두통, 포진후신경통, 신경병변성통증같은신경이나혈관의장애등을들수있다. 심리적인요인은정신적혹은심리적문제로신체적증상을호소하는경우를들수있다. 사회및정서적요인들은통증에의한결과일수도있고주원인일수도있으며, 통증을유지하는주된요인일수있다. 구강안면통증환자의인성에대한심리적인고찰은우울증, 무쾌락증과불안, 질병행동과인성, 치료전후의인성특성등에대해보고된바있다 [5-7]. 구강안면통증을조절및치료하기위해교합장치치료 (splint), 약물치료, 물리치료, 그리고심리치료등다양한
2 Dong-Woo Kang and Young-Kyun Kim 방법을사용할수있다. 물리치료는온열요법, 냉각요법, 이온삼투요법, 경피성전기신경자극요법, 침술및레이저치료등이있으나, 이를바탕으로한연구들은대부분임상경험을기초로하여과학적인기반은부족한실정이다. 본연구의목적은원인을명확하게알수없는구강안면통증을가진환자들의증상과진단, 임상적치료과정및예후를평가하고효과적인치료방법을모색하는것이다. Table 1. Classification of diagnosis Diagnosis Atypical facial pain 22 Traumatic neuropathy 17 Trigeminal neuralgia 14 Psychologic pain 5 Atypical odontalgia 3 Total 61 재료및방법 2003년부터 2016년까지분당서울대학교병원구강악안면외과에내원한구강안면통증을호소하는환자들중치성통증, 감염, 골수염, 턱관절질환등원인이명확하게밝혀진질환을제외한 61명의환자들을연구대상으로하였다. 13명의남성, 48명의여성으로평균연령은 60.8세였다. 감별진단을위해환자들의임상증상및병력을청취하고주된증상과부가적인증상을조사하고, 필요에따라영상의학적검사 ( 일반방사선검사, CT, MRI, bone scan), 혈액검사, 체열검사 (Thermography), 전기치수검사, 전기생리학적검사, 진단목적의국소마취등을시행하였다. 치료방법으로는환자의정밀진단과증상등여러가지상황을고려하여상담치료, 약물치료, 물리치료, 치아치료, 치주치료, 외과적수술등을시행하였다. 의무기록지를후향적으로조사및분석하여환자들별로진단을세분화하였고, 진단에따른치료기간과치료예후를평가하였다. 진단은심인성통증 (psychologic pain), 외상성신경병변증 (traumatic neuropathy), 삼차신경통 (trigeminal neuralgia), 비특이성안면통증 (atypical facial pain), 비특이성치통 (atypical odontalgia) 군으로, 총 5개로분류하였다. 치료예후는임상적및환자의주관적인반응을바탕으로 1:excellent, 2:good, 3:favorable, 4:static, 5:poor 등으로평가하였고, 이를각군별로평균내었다. 이전연구에서도유사한방법으로치료경과및예후를평가한바있다 [8,9]. 본임상연구는분당서울대학교병원생명윤리심의위원회의승인 (IRB: B-1610/ ) 하에시행되었다. 들을기반으로하여이루어졌으며, 필요에따라부가적인검사들이시행되었다. 기본적인문진, 방사선사진과함께턱관절의진행성병변이나과두의흡수가의심되거나, 정밀검사가필요한경우 Bone scan이나 CT촬영을시행하였고, 심한개구제한및악성병소가의심되는경우에 MRI 를촬영하였다. 다른전신적인질환이의심되거나염증성병소가의심될경우에는의심될경우에혈액검사도시행하였고, 외상성신경병변증이의심되는환자들은체열검사및정량적감각검사 (QST: Quantitative Sensory Test) 도시행하였다. 그외에는삼차신경통혹은감각이상등의증상이의심될경우근전도검사 (EMG: electromyography), 정량적감각검사, 체성감각유발전위검사 (SEP: somatosensory evoked potential), 안와하신경전달마취등도선별적으로시행하였다. 치성통증의감별이필요한경우는전기치수검사 (EPT: electric pulp test) 도시행하였다 (Table 2). 환자별로치료방법은다양했는데, 기본적인약물치료가 63명으로가장많 Table 2. Types of examinations Examinations Radiographs 61 CT 13 MRI 4 Bone scan 22 Blood test 12 Thermatography 3 Etc. 6 Etc.: SEP, QST, EPT, EMG, Infraorbital nerve block. Table 3. Types of treatments 결과 61명의구강안면통증을호소하는환자들의평균치료기간은 32개월이었다. 연구대상자들은여성환자들이 78.7% 를차지하여남성환자들에비해서많았으며, 전체환자들의평균나이는 60.8세였다. 세부진단은비특이성안면통증군이 22명으로가장많았고, 외상성신경병변증군이 17명으로그뒤를이었다 (Table 1). 진단은임상증상 Treatment Medication 61 Physiotherapy 21 Periodontal treatment 16 Surgery 11 Prosthetic treatment 9 Consultation 6 Endodontic treatment
3 A retrospective clinical study 았고, 물리치료가 21명으로그뒤를이었다 (Table 3). 약물은보통소염진통제 (NSAIDs, COX-2 inhibitors), 항생제, carbamazepine, gabapentin, nortriptyline, 보툴리눔톡신, 항우울제, 비타민제 (Beecom, Vitamin B12), 각종연고및가글액 (capsaicin ointment, Extractum chamomillae ointment, ketoprofen ointment, dexamethasone gargle) 등을선별적으로사용하였다. 물리치료는주로레이저치료와전기침자극요법 (EAST: Electric Acupuncture Stimulation Therapy) 이시행하였다. 보철치료는주로보철물을제거한경우가많았는데, 협심증이나심근경색같은심장성치통, 외상성신경병변증, 금이간치아 (crack tooth syndrome) 등이의심되면서, 진단을명확히내릴수없는통증을호소하는경우에시행하였다. 혀에심한통증을호소한환자에게는보철물재제작, 교합조정, 혀의자극을제한하는보철물 (tongue protector) 제작등을시행하였다. 수술적접근법으로는임플란트지대주제거, 치근단절제술, 전정성형술, 절개및배농술, 삼차신경절단술, 감마나이프수술등을시행하였다. 치주치료는임플란트주위염이있을경우소파술혹은레이저치료를시행하였고, 각화치은이부족한경우에각화치은형성술을시행하기도하였다. 근관치료는전기치수검사에반응없는경우, 금이간치아등에서선별적으로시행하였다. 상담치료의경우에는자세한병력청취및자세한의무기록작성과함께충분한시간을할애하여호소하는증상에대해상담을시행하였다. 치과외적인진료가필요한경우정신건강의학과, 신경과, 재활의학과, 마취통증의학과, 이비인후과등에의뢰하여협진을시행하였다. 임상진단별로평균치료기간을분석한결과삼차신경통군이 52.9개월로가장치료가장기화되었고, 비특이성치통군이 16.3개월로가장치료기간이짧았다 (Table 4). Table 4. Duration of treatment Diagnosis Month Trigeminal neuralgia 52.9 Psychologic pain 37.2 Traumatic neuropathy 29.1 Atypical facial pain 26.6 Atypical odontalgia 16.3 Table 5. Clinical prognosis of diagnosis Diagnosis Outcome Atypical facial pain 2.80 Traumatic neuropathy 2.70 Trigeminal neuraliga 2.60 Psychologic pain 2.40 Atypical odontalgia : excellent, 2: good, 3: favorable, 4: static, 5: poor. 치료경과로는비특이성치통이 2.00으로가장양호하였으며, 다음으로심인성통증, 삼차신경통, 외상성신경병변증, 비특이성안면통군순이었다 (Table 5). 환자들이호소하는주된증상외에부가적인증상들은특별히다른증상이없는경우가 55명, 안면부부종이 3명, 상악동염이동반된경우가 2명, 정신과적질환으로치료를받는환자가 2명, 구강내궤양 2명, 구강건조증으로불편감을호소하는환자가 1명, 턱관절통증 1명등으로분석되었다 (Table 6). 부가증상들은 1명의환자는상악동염과안면부부종이복합되어나타났다. 구강안면통증이발생하게된소인을추정, 분석해보았을때, 원인을알수없는경우가 27명, 임플란트수술후발생한경우가 18명, 보철물장착이후발생한경우가 7명, 발치후발생한통증이 5명, 근관치료후발생한경우가 4명, 치과마취후발생한설신경손상의경우가 2명, 하치조신경전위술이후발생한경우가 1명, 의치장착후발생한경우가 1명, 이갈이로발생한통증인경우가 1명, 뇌종양제거후발생한통증이 1명등으로조사되었다 (Table 7). 1명의환자는임플란트, 근관치료, 보철물장착등의소인이복합되었다. 임상및부가적검사를진행하면서발견된특이소견으로는특이소견이없는경우가 51명, 치조골소실이 5명, Bone scan 검사상턱관절및안면부위증가된섭취율 (increased uptake ratio) 을보인경우가 3명, 치근단병소가있는경우 Table 6. Types of additional symptoms Additional symptoms No specific 55 Swelling 3 Sinusitis 2 Mental abnomality 2 Ulcerative lesion 2 Dry mouth 1 Temporomandibular disorder 1 Table 7. Origin for diseases Origin for disease Unknown 27 Dental implant 17 Prosthesis 7 Extraction of tooth 5 Endodontic treatment 4 Dental anesthesia 2 Inferior alveolar nerve transposition surgery 1 Denture 1 Bruxism 1 Removal of brain tumor
4 Dong-Woo Kang and Young-Kyun Kim Table 8. Clinical & Radiological findings Specific findings No specific 51 Periodontal bone loss 4 Increased uptake 3 Apical bone lesion 3 Paresthesia 3 가 3 명, 감각이상이 3 명등으로조사되었다 (Table 8). 고 찰 구강안면통증은구강안면부위의중추혹은말초신경계에서발생한구조적또는기능적비정상에의해발생한다. 구강안면부위에서표정, 저작, 발음등의섬세한근육운동이이루어지고감각이다른부위보다예민하기때문에구강안면통증은미약할지라도환자들의불편감을호소하는정도가다른통증보다크게나타난다. 초기에서는체성감각성통증이주로나타나지만, 만성화될수록사회심리학적인측면이점점커지게된다. 구강안면통증은다양한위치에서발생할수있으며병인론또한매우다양하다. 심인성통증은애매모호한통증을호소하는경우로, 체성화와같은심리적문제가관여되며, 신체에는아무런이상이없지만심리적혹은정신적문제때문에치통이나안면통이유발되는경우를의미한다. 주로통증은여러치아혹은여러군데에서나타나고, 다양한부위로옮겨다니는양상을보이며통증이생길만한원인을발견할수없고, 치과치료에반응을보이지않아, 정신과적인치료가필요하다. 본연구에서심인성통증으로진단한경우도명확한통증유발요인이없으며, 정상소견을보인경우가대부분이었고, 정신건강의학과진료를받은병력등을참고하여진단을내렸다. 외상성신경병변증은신경손상과관련되어발생하는통증으로, 주된원인은제3대구치의수술적발거, 하악신경전달마취, 임플란트수술, 근관치료등의의원성손상및외상이고, 간혹바이러스감염, 방사선치료, 악성종양의전이등에의해서도발생하기도한다. 증상은감각이둔화된증상을나타내는경우도있고, 지각이상, 이상감각, 통증등과같이감각이비정상적으로민감해지는경우도있다. 주로지속적이거나발작성의통증과함께불쾌한감각이함께발현되고염증성통증과는달리비스테로이드성소염제에는거의반응을보이지않는다. 항우울제, 항경련제등으로통증을조절할수있으나완치시키는약물은개발되어있지않다. 삼차신경통은삼차신경의발작성흥분에의해나타나는 통증으로, 주로얼굴의한쪽에서전기가통하는듯이극심하고날카로운통증이나타난다. 갑자기통증이발현되며, 얼굴, 잇몸, 치아의통증으로나타나기도한다. 통증이한번지나간후에는다음통증발현될때까지통증이없으며항경련제를투약하거나경피적신경블록술혹은뇌감압술등의수술적방법도고려해볼수있다. 비특이성안면통은뇌신경의특성을가지지않고다른진단에해당되지않으며지속되는통증이특징적이다. 약물치료, 심리치료, 물리치료, 외과적수술등이사용되며, 주로삼환성항우울제와항경련제를사용한다. 비특이성치통은임상적, 방사선학적검사에서정상소견을보이지만만성적인통증을나타내고치과치료에반응을보이지않는것이특징이다. 종종치수염과유사한증상을호소하고지속적인격통을보인다. 구강안면통증의치료원칙은치성통증인지비치성통증인지감별을먼저해서치성통증이면, 교합조정, 근관치료, 치주치료등을시행하여증상의경감유무를판단해보아야한다. 비치성통증이면감별진단및치료계획이훨씬복잡할수있다. 물리치료가효과가있는것으로알려져있는데, 환자에게온열찜질또는냉각요법을적용하거나, 혹은두가지방법을번갈아서적절히사용하면효과가좋다고한다. 그이유는진통및근이완효과를주어안면운동기능을향상시켜주고구강안면통증을개선시켜주기때문이다 [10-13]. 약물치료도악안면통증에효과적인치료방법이다 [3]. 주로사용하는약물로는비스테로이드소염진통제, 국소마취, 코티코스테로이드, 근이완제, 항히스타민제, 보툴리눔톡신주사, 항우울제등이있다 [14-16]. 수술적접근은주로삼차신경통으로진단받은경우비수술적치료에효과가없는경우에한해서고려해볼수있다. 본연구에서치료방법은치성통증을유발할만한요인이있는경우는근관치료, 치주치료, 보철치료, 절개및배농술등원인을제거하는치과적인치료가시행되었고, 심리적통증환자들은항우울제, 항경련제등의약물치료, 물리치료등의보존적인치료와환자의강력한요구로임플란트를제거하기도하였으며정신건강의학과의진료도함께한경우도있었다. 외상성신경병변증으로진단된환자들은 gabapentin, carbamazepine, 항우울제, 비타민제제, 스테로이드등의약물치료, 전기침자극요법이나레이저치료같은물리치료, dexamethasone 주입, 보툴리눔톡신주입, 캡사이신연고, soft splint 장착, omnivac neurostent (Stent 착용하면서내면에 capsaicin 연고도포 ), 마취통증의학과와협진등으로치료했다. 삼차신경통환자들은 carbamazepine, gabapentin, 항우울제등의약물치료, 보툴리눔톡신주입, dexamethasone gargle, 레이저혹은전기침자극요법물리치료, 신경절제술, 마취통증의학과와협진하
5 A retrospective clinical study 여성상신경절블록술 (stellate ganglion block), 뇌신경센터와협진하여감마나이프수술을통한감압술등을시행하였다. 비특이성안면통은 carbamazepine, 항우울제, imotun 등의약물치료, dexamethasone gargle, 마취통증의학과, 뇌신경센터등의협진을통한상담치료, 레이저나 ozonytron 물리치료, splint 치료, 이비인후과와협진등을시행했다. 비특이성치통은항생제, carbamazepine 등의약물치료, Admuc 연고, 레이저물리치료, 임플란트제거술등을시행했다. 본연구에서는통증을유발할만한치과적소인들이추정되었던환자들에게치과적치료가시행되었다. 즉, 17 명에서치주치료, 9명은보철치료, 4명은근관치료가병행되었다. 더불어약물치료 63명, 물리치료 21명등악안면통증을호소하는대부분의환자에게서보존적인치료법이시행되었고, 보존적인치료법에효과가없는 12명의환자들에게서는외과적치료가시행되었다. 치과적치료가시행된경우는치료과정중에병소가발견된경우도있었고통증을유발할만한원인들이명확하지않아소인들을제거하기위한방법으로시행한경우가더많았다. 수술적인치료는 12명의환자들에서시행되었는데, 6명의환자는임플란트주위염, 신경통, 골수염등이존재하여임플란트를제거하였고, 4명의환자는구강악안면외과에서삼차신경절제술혹은뇌신경센터에서 microvascular decompression 혹은 gamma knife radiosurgery 같은 neurosurgical treatment를시행하였고, 1명의환자는각화치은증대술, 1명의환자는치조골성형술을시행하였다. 수술적치료를받은환자들은대부분수술후증상의경감을보여주었다. 삼차신경통을호소하는환자들중일부는마취통증의학과와협진하여성상신경절블록술을시행하기도하였는데, 큰효과를보지는못했다. 성상신경절블록술은교감신경을차단하여혈류를증가시키고신경섬유로의혈행을개선하여신경섬유재생이촉진될수있다. 삼차신경통에는항간질약이효과가있는데, carbamazepine, oxcarbazepine 및 gabapentin이첫번째선택옵션으로잘알려져있다 [17,18]. 이러한약물들이효과가없거나부작용으로인해대체약물이필요하면두번째선택옵션으로 baclofen과 lamotrigine이통증조절에도움이될수있다 [19,20]. 그러나고용량의 carbamazepine은백혈구감소증, 부종, 알레르기, 저나트륨혈증등의부작용을초래할수있어장기간복용시에는정기적으로혈액검사를하는것이좋다. 임상진단별로평균치료기간을분석한결과삼차신경통군이 52.9개월로가장치료가장기화되었고, 비특이성치통군이 16.3개월로가장치료기간이짧았다 (Table 4). 치료경과로는비특이성치통이가장양호했으며, 심인성통증, 삼차신경통, 외상성신경병변증, 비특이성안면통순이었다 (Table 5). 삼차신경통의경우주로통증을완화하 는약물요법이주된치료이며, 경피적신경블록술혹은뇌감압술, 신경절단술등의침습수술적방법에대한부담감으로인해수술이지연되면서치료기간이매우길어진것으로생각된다. 구강안면통증은대체로치료가쉽지않고, 예후도좋지않은것으로알려져있다. 환자의협조도도부족하며, 그에따라치료기간도길어지는경향이있다. 본연구에서도치료기간이장기화된경우가많았지만, 여러치료를병행하면서소인을제거하려고시도하는과정에서환자의주관적인증상이경감되고심리적으로도회복되는양상들이관찰되었다. 이처럼구강안면통증을치료하기위해서다양한병인론에대한이해가필요하며, 발생할수있는증상들에대한감별진단이중요하다. 다방면의진단학적방법을이용하여진단하고치료계획을수립하는것이중요하다. 결 론 원인불명의구강안면통증을호소하는환자에게현재시행하고있는약물치료및물리치료의예후는대체로효과적인것으로나타났다. 환자가호소하는증상및임상적인검사를통해추가적인검사가적절히시행되어정확한감별진단을시도해야하며그에따라적절한처치가시행되면우수한치료경과를보일수있을것으로보인다. 만성구강안면통증을보이는환자들의더발전된치료를위해서다양한연구가필요하다. Conflict of Interest The authors declare that they have no competing interests. ORCID Dong Woo Kang Young-Kyun Kim References 1. Kreisberg MK, Rosenbaum RW, Gross SG, Hayek RR, Cashman SM. The scope of TMD/orofacial pain (head and neck pain management) in contemporary dental practice. J Oral Facial Pain Headache 1997;11: Okeson JP. Bell s orofacial pain. 5th ed. Chicago: Quin
6 Dong-Woo Kang and Young-Kyun Kim tessence; Okeson JP. Bell s orofacial pains. The Clinical Management of Orofacial Pain. 6th ed. Carol Stream, IL: Quintessence Publishing Co, Inc; Okeson JP. The classification of orofacial pains. Oral Maxillofac Surg Clin North Am 2008;20: doi: /j.coms Marbach JJ, Lund P. Depression, anhedonia and anxiety in temporomandibular joint and other facial pain syndromes. Pain 1981;11: Gordon A, Hitchcock ER. Illness behavior and personality in intractable facial pain syndromes. Pain 1983;17: Mongini F, Ibertis F, Ferla E. Personality characteristics before and after treatment of different head pain syndromes. Cephalgia 1994;14: doi: /j Massager N, Lorenzoni J, Devriendt D, Desmedt F, Brotchi J, Levivier M. Gamma knife surgery for idiopathic trigeminal neuralgia performed using a far-anterior cisternal target and a high dose of radiation. J Neurosurg 2004;100: doi: /jns Holland M, Noeller J, Buatti J, He W, Shivapour ET, Hitchon PW. The cost-effectiveness of surgery for trigeminal neuralgia in surgically naiv epatients: a retrospective study. Clin Neurol Neurosurg 2015;137: doi: /j.clineuro de Leeuw R, Klasser GD. Orofacial pain: guidelines for assessment, diagnosis, and management. Am J Orthod Dentofacial Orthop 4th ed. Hanover Park, IL: Quintessence Publishing Co, Inc; p Danzig WN, Van Dyke AR. Physical therapy as an adjunct to temporomandibular joint therapy. J Prosthet Dent 1983;49: doi: Rakhshan V. Common risk factors for postoperative pain following the extraction of wisdom teeth. J Korean Assoc Oral Maxillofac Surg 2015;41: doi: / jkaoms Zdilla MJ. Screening for variations in anterior digastric musculature prior to correction of post-traumatic anterior open bite by injection of botulinum toxin type A: a technical note. J Korean Assoc Oral Maxillofac Surg 2015; 41: doi: /jkaoms Gangarosa L, Mahan PE. Pharmacologic management of TMJ-MPDS. Ear Nose Throat J 1982;61: Gregg JM, Rugh JD. Pharmacological therapy. In: Mohl NDZ, George A, Carlsson, Gunnar E, Rugh, John D, editor. A Textbook of Occlusion. Chicago, IL: Quintessence; p Song PC, Schwartz J, Blitzer A. The emerging role of botulinum toxin in the treatment of temporomandibular disorders. Oral Dis 2007;13: doi: /j x. 17. Kitt CA, Gruber K, Davis M, Woolf CJ, Levine JD. Trigeminal neuralgia: opportunities for research and treatment. Pain 2000;85:3-7. doi: /S (99) Zakrzewska JM. Medical management of trigeminal neuropathic pains. Expert Opin Pharmacother 2010;11: doi: / Fromm GH, Terrence CF, Chattha AS. Baclofen in the treatment of trigeminal neuralgia: Double-blind study and long-term follow-up. Ann Neuro 1984;15: doi: /ana Zakrzewska JM, Chaudhry Z, Nurmikko TJ, Patton DW, Mullens EL. Lamotrigine (lamictal) in refractory trigeminal neuralgia: results from a double-blind placebo controlled crossover trial. Pain 1997;73: doi: / S (97)
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