trigeminal neuralgia ( tn ) is the most common neuralgia , with an annual incidence of 5/100000 . the international association for the study of pain ( iasp ) defines tn as sudden , usually unilateral , severe , brief , stabbing , and recurrent episodes of pain in the distribution of one or more branches of the trigeminal nerve . treatment guidelines , published from the american academy of neurology ( aan ) and the european federation of neurologic societies ( efns ) , recommend carbamazepine or oxcarbazepine as the first choice pharmacological treatment of tn and baclofen or lamotrigine as the second choice . however , some patients may experience intractable pain despite adequate treatment with these medications or their combination . on the other hand , some patients may experience intolerable side effects that lead to discontinuation , although recommended treatments have achieved sufficient reduction of their pain . it is mainly used to relieve cancer or postoperative pain [ 4 , 5 ] , however , it has also been used to relieve several kinds of neuropathic pain , including postherpetic neuralgia   and intractable tn [ 7 , 8 ] . this therapeutic potential lies in the fact that systemic lidocaine and its oral congeners can block sodium channels in a dose dependent fashion [ 9 , 10 ] in both the peripheral and the central nervous system . in the literature , the aim of our randomized double blind , placebo controlled , crossover study was to investigate in a prospective way the effect of lidocaine in patients with tn . following the approval of the institutional ethical committee of aretaieion hospital , university of athens , all consecutive patients suffering from tn who visited the outpatient pain and palliative care center were invited to participate in the study . to be enrolled , the patients had to meet the following inclusion criteria : ( 1 ) confirmed diagnosis of tn according to iasp definition , ( 2 ) age equal to or greater than 18 years , ( 3 ) visual analogue scale ( vas ) score equal to or greater than 3 ( out of a maximum 10 ) , ( 4 ) douleur neuropathique 4 questionnaire ( dn4 ) score equal to or greater than 4 ( out of a maximum 10 ) , ( 5 ) having received the recommended medications for tn ( antiepileptics , spasmolytics , opioids , anti - inflammatory , and simple analgesic drugs ) for an adequate period without therapeutic results , ( 6 ) tn duration of at least 12 months , ( 8) no history of allergy to lidocaine , ( 9 ) no history of substance abuse , ( 10 ) absence of severe psychiatric diseases , ( 11 ) not being pregnant , ( 12 ) not lactating , ( 13 ) absence of severe cardiac , hepatic , and renal decease , and ( 14 ) be willing to provide a written informed consent to undergo the experimental procedures . each patient participated in four sessions , every 2nd day , receiving two active and two placebo treatments , involving continuous infusion of 1 hour . active treatment was lidocaine ( 5  mg per kilogram of body weight ) in 250  ml of 5% dextrose solution and placebo treatment was 250  ml of 5% dextrose solution . investigator b , who was blind to the treatment , was responsible for clinical examination and treatment administration . at the end of each treatment investigator b had to record data and enclose the forms in envelopes that remained closed until the end of the study . in the morning of each session ( 08:00 ) the patients were guided to a calm and separate room where investigator b recorded the pain intensity on vas before the beginning of the infusion and at the end of it . moreover , investigator b tested the intensity of ( 1 ) mechanical allodynia ( pressure of the painful area by an unused pencil ) , ( 2 ) thermal allodynia ( application of a thermal roll at 40c at the painful area ) , ( 3 ) cold allodynia ( application of a thermal roll at 26c at the painful area ) , ( 4 ) pinprick hyperalgesia ( feeling excess pain more than usual pain during the pinprick by a needle 26 g at the painful area ) , ( 5 ) hot hyperalgesia ( application of a thermal roll at 46c at the of the painful area ) , and ( 6 ) cold hyperalgesia ( application of a thermal roll at 20c at the painful area ) . during the sessions the patients were monitored continuously by 3-lead electrocardiogram , pulse oximetry , and blood pressure ( bp ) manometer . every 15 minutes systolic bp , diastolic bp , oxygen saturation , and heart rate ( hr ) were recorded . any side effects , such as somnolence , mental confusion , metal taste , tingling sensation around the mouth , vision disturbances , tremor , drowsy mouth , tremor , or anything else were also documented . pain diary ,  where they recorded the vas score at 16:00 , 20:00 , and 24:00 the same day and at 08:00 the next morning . a database was developed using the statistical package for social science ( version 16.0 for mac ; spss ) . comparisons between patients who received lidocaine and patients who received placebo were made using student 's t - tests for normally distributed continuous data and mann - whitney 's u test for nonnormally distributed data . allodynia and hyperalgesia were graded according to a likert scale from 0 to 4 ( 0 = no pain , 1 = little pain , 2 = moderate pain , 3 = heavy pain , and 4 = unbearable pain ) . patients who achieved a reduction of at least 1 grading point in the likert scale were considered to have achieved a reduction of allodynia and hyperalgesia , when patients who either graded the same before and after or showed increase in the likert scale were considered not to have achieved a reduction . comparisons between the lidocaine and placebo groups regarding these categorical data were made using the chi - square test . power analysis demonstrated that a 20% difference in vas reduction with 80% power could be detected with a sample of 20 patients . a value of p < 0.05 was considered to be statistically significant . between february 2007 and september 2011 , 23 individuals fulfilled the above - mentioned inclusion criteria . clinical and demographic characteristics of the study total population are summarized in table 1 . table 2 shows the response regarding intensity of pain , allodynia , and hyperalgesia following lidocaine versus placebo intravenous infusion . both lidocaine and placebo reduced the intensity of pain , at the end of each session ; however , lidocaine achieved a greater reduction compared to placebo ( 76.4% versus 40.1% , p < 0.001 ) . this was maintained for at least 24 hours after treatment as was documented in the pain diary . hence , at 24 hours after treatment lidocaine achieved a reduction of 52% of the pretreatment intensity of pain when patients who received placebo reported a mild increase of 4% of the pretreatment intensity of pain ( figure 1 ) . similarly , lidocaine reduced mechanical allodynia thermal allodynia , cold allodynia , pinprick hyperalgesia , hot hyperalgesia , and cold hyperalgesia in a statistically significant greater percentage of patients . no statistically significant changes regarding systolic bp , diastolic bp , hr , and oxygen saturation were found during the treatment administration between patients who received lidocaine and patients who received placebo . 
 table 3 summarizes the adverse events as reported by the patients after each treatment . most common side effect among patients who received lidocaine was somnolence ( reported in 32.5% of cases ) and most common side effect among patients who received placebo was dry mouth ( reported in 5% of cases ) . this double blind , randomized , crossover , placebo controlled study aimed to investigate the effect of intravenous lidocaine on trigeminal neuralgia . we showed that intravenous lidocaine is superior regarding the reduction of the intensity of pain , the allodynia , and the hyperalgesia compared to placebo and that lidocaine managed to maintain its therapeutic results during the first 24 hours after intravenous infusion . to our knowledge , this is the first prospective study of the effect of intravenous lidocaine on trigeminal neuralgia compared to placebo . moreover , in a nonclinical setting not many studies examining the alteration of the evoked pain of tn by the intravenous administrations of lidocaine exist . an experimental study in neuropathic rats had already shown that intravenous , but not intrathecal or regionally applied , lidocaine produces dose dependent suppression allodynia associated with nerve injury . interestingly enough , the effects far outlast plasma concentrations of lidocaine ; however , the mechanism of these prolonged effects remains unknown . in our study we also observed that lidocaine achieved a decrease of the intensity of pain , as this was measured by vas , which lasted for 24 hours and this decrease was superior compared to placebo , despite the fact that lidocaine 's half - life is 1,6 hours . similar to this , tremont - lukats et al . reported that the effect of lidocaine in patients with neuropathic pain started 4 hours after the onset of treatment and continued for at least 4 hours after the end of the infusion . moreover , attal et al . showed that , in patients with central pain , lidocaine decreased vas for 6 hours after the injection and a subgroup of patients experienced prolonged analgesia for up to 7 days . furthermore , arai et al . claimed that in some patients who suffered from trigeminal neuralgia and had pain relief after receiving lidocaine and magnesium the therapeutic result lasted for almost one year . until now , the effectiveness of lidocaine in neuropathic pain has been shown through case series . series concluded that the use of 5% lidocaine plasters may be a useful adjunctive tool for the management of chronic orofacial pain . interestingly , several patients in this study commented that the plasters significantly assisted breakthrough pain , particularly cold allodynia caused by exposure of the face to cold air resulting in excruciating pain . moreover , arai et al . have recently published data of nine patients with tn treated with an intravenous infusion of a combination of 1.2  g magnesium and 100  mg lidocaine for 1 hour , once a week for 3 weeks . the authors concluded that all patients experienced sound pain relief after the combined intravenous infusion therapy . however , as their study was performed in a retrospective way , the authors did not use a control group . the authors explain that because of the very low incidence of intractable tn it is impractical to perform a randomized placebo controlled trial . as we also had difficulty in identifying a large sample of patients to be recruited in the form of a randomized placebo controlled trial we performed a crossover trial . thus , each patient participated in four sessions , receiving two active and two placebo treatments . this is a very good alternative way to study different drug types and/or doses when the study sample is small . one other advantage of our study is that we used a standardized dose of lidocaine according to the patients ' weight . we chose to use the dose of 5  mg / kgr lidocaine over 60 minutes because in this dose lidocaine does not affect the peripheral conduction [ 19 , 20 ] and it , also , acts at hyperexcitable neurons without affecting normal nerve conduction showing , thus , good effects on neuropathic pain . regarding its safety profile , intravenous lidocaine has been used to relieve several kinds of neuropathic pain without producing major adverse effects . similarly , in our study , the infusions caused minor side effects and during the infusions all the patients were haemodynamically stable with good oxygen saturation . finally , our results should be interpreted with some caution given the fact that we only used a single dose of lidocaine ( 5  mg / kg ) . however , such procedures involve the risk of major neurological complications and other less serious adverse effects and their result may not last . although intravenous lidocaine is not a first line treatment , when first line medications fail to help , pain specialists may try it as an add - on treatment .
trigeminal neuralgia is the most common neuralgia . 
 its therapeutic approach is challenging as the first line treatment often does not help , or even causes intolerable side effects . 
 the aim of our randomized double blind , placebo controlled , crossover study was to investigate in a prospective way the effect of lidocaine in patients with trigeminal neuralgia . 
 twenty patients met our inclusion criteria and completed the study . 
 each patient underwent four weekly sessions , two of which were with lidocaine ( 5  mgs / kg ) and two with placebo infusions administered over 60 minutes . 
 intravenous lidocaine was superior regarding the reduction of the intensity of pain , the allodynia , and the hyperalgesia compared to placebo . 
 moreover , contrary to placebo , lidocaine managed to maintain its therapeutic results for the first 24 hours after intravenous infusion . 
 although , intravenous lidocaine is not a first line treatment , when first line medications fail to help , pain specialists may try it as an add - on treatment . 
 this trial is registered with nct01955967 .