10th World Congress on Pain, List of topics

HEADACHE: THE MOST PREVALENT BODY SYMPTOM IN SARDINIAN AND LEBANESE DENTAL STUDENTS
Y. Abou-Atme, A. Pittau², M. Melis School of Dentistry, Saint Joseph University, Beirut, Lebanon , School of Dentistry, Universit degli Studi di Cagliari, Calgari, Italy

Aim of Investigation: It is not known whether body symptoms differ between different dental populations. This study was conducted to determine prevalence of common body pain symptoms in two different dental students populations.

Methods: All one hundred and seventy eight dental students (N1=178 out of 178; 117 Males/61 Females) of Saint Joseph University Beirut and one hundred and fourteen dental students (N2=114 out of 115; 60 males/54 females) of the University of Cagliari answered a 0-3 numeric visual analog scale body symptom questionnaire. Symptoms listed were earache, ear stuffiness, Temporomandibular joint TMJ Pain, TMJ sounds, headache, face pain, arm symptoms, neck pain, upper back, lower back, toothache. The Chi-Square test applied to a 2x2 table was used for statistical analysis.

Results: The most prevalent symptom in both groups was headache (57% USJ vs. 51% USC), Followed by neck pain (45% USJ vs. 40% USC). The least prevalent symptom was face pain. In both populations, headache was found significantly more common in females than males (USJ P<0.05, USC P<0.01). Both groups did not show significant differences in body symptom prevalence except for earache (P< 0.05).

Conclusion: This study suggests that headache should be the number one symptom investigated in dental students. Future studies should put more emphasis on the cause of this phenomenon and the ways to prevent it.

ESTIMATE SERTRALINE EFFICACY AS A PROPHYLACTIC DRUG IN MIGRAINE MANAGEMENT.
Z.S. Adwan Dept of Neurology, Zyd Shariti Hospital, Swaida, Syria

AIM OF INVESTIGATION: To estimate the efficacy of SERTRALINE as a prophylactic drug in migraine management.

METHODS: One hundred (100) patients with defined common and typical migraine, having had more than 3 migraine attacks per month, participated in the study. Patients were given SERTRALINE in 50 mg single doses for 3 consecutive months and were checked monthly for symptoms and side effects.

RESULTS: The frequency of migraine attacks decreased progressively during the 3 months of treatment and more than 90% obtained relief from the attacks. Patients who were having severe nausea and vomiting obtained progressive relief from these symptoms during treatment, and 80% of the patients obtained relief from vomiting. Patients suffering from photophobia and phonophobia improved progressively, and after 3 months of treatment, more than 85% had obtained relief from the main symptoms.

CONCLUSIONS: The use of SERTRALINE as a prophylactic drug in migraine management could be a new good approach.

ACHIEVEMENT MOTIVATION IN ADOLESCENTS WITH HEADACHE
M. Mehta, E. Mukhim, R. Sagar Psychiatry, All India Institute of Medical Sciences, New Delhi, India

AIM OF INVESTIGATION: To evaluate achievement motivation in adolescents having headache

METHODS: The study group was comprised of 40 adolescents (25 males, 15 females) in age range 11-16 years with primary diagnosis of headache. 20 patients were diagnosed with migraine according to the Headache Classification Committee, (1988) and 20 patients were diagnosed as tension type headache. Patients with organic causes of headaches like sinusitis, refractive errors and coexisting medical disorders were excluded. Informal consent was taken from all the subjects. To assess achievement motivation following methods were used 1) semi-structured schedule 2) Family Environment Scale (Moor & Moor 1986) and 3) Thematic Apperception Test (Murray).

RESULTS: Presence of high ambitions, perfectionists traits and need to succeed were observed in the adolescents with migraine {70%} and tension type headache {47%}. Parents also had high expectations in academic achievement. On FES higher scores on achievement orientation and control sub-scales were obtained.

CONCLUSION: Adolescents with migraine had higher achievement motivation than tension headache group. This aspect needs to be included in the management of headache.

CHRONIC HEADACHE FOLLOWING NORMAL PRESSURE HYDROCEPHALUS SURGERY
S. Adel, F. Elahi, M. Nabavi neurosurgery, mostapha khomaini hospital, tehran, Iran , neurology, shahed university hospital, tehran, Iran

AIM OF INVESTIGATION: To assess the reasons for headache following NPH surgery; a prospective cohort study.

METHODS: 152 cases with the diagnosis of idiopathic NPH underwent ventriculoperitoneal medium pressure shunting, fuji type. They were classified as short onset (less than 6 months) and long onset (after 6 months) headache.

RESULTS: Most of these patients had long onset headache, for the short onset undershunting and overshunting was the main cause for headache, and for the long onset lacunar infarct and tension type headache was among the common etiologic factors.

CONCLUSION: NPH never accompanied by headache and when a clinician encountered a case of headache, NPH would be automatically ruled out. We will attempt to explain the cause and effect of surgery and headache in this paper.

RELATIONSHIP BETWEEN DEPRESSION AND MIGRAINE IN WOMEN. A LONGITUDINAL STUDY.
F. Mongini, R. Keller, A. Deregibus, F. Raviola, T. Mongini, M. Sancarlo Dept. of Clinical Pathophysiology, Headache Unit, University of Turin, Torino, Italy

Aim of investigation: To examine the association between migraine and depression in women.

Methods: In 56 women with migraine depression was assessed with a structured interview and the MMPI and STAI were administered. Headache characteristics were recorded before treatment (T 0), after treatment (T1), and six years later (T2). Patients were assessed according to: presence of major depression at T 0, and improvement or no improvement of migraine at T 2. The pain characteristics in the three periods and the MMPI and STAI data at T 0 were statistically examined according to these two criteria (ANOVA, Student t, and Chi square analysis). Multiple regression analysis was also performed taking the MMPI and STAI scores at T 0 as independent variable and the pain parameters at T 0, T1 and T2 as dependent variable.

Results: At T 0 55.4% patients had major depression and 44.6% had not. Pain parameters in both groups were similar at T 0 and improved at T1; at T2 they further improved in the not depressed group but worsened in the depressed group. At T2 57.2% patients had improved and 42.8% patients had not. In the improved patients the prevalence of depression and the majority of MMPI and STAI scores were at T 0 significantly lower than in the not improved patients. After multiple regression analysis, headache frequency at T2 correlated with the MMPI depression score and with STAI 1,2 scores at T 0.

Conclusions: A bi-directional relationship seems to subsist between woman migraine and depression. The co-occurrence of depression and migraine appears to be influential on the headache history in the long term.

Acknowledgments: Supported by a grant from the Italian Ministry of Education.

LONG LASTING EFFECT OF SIMULTANEOUS USE OF ELECTRICAL STIMULATION OF NUCHEAL REGION PLUS IBUPROFIN AND IMIPRAMINE IN MANAGEMENT OF RECURRENT INTRACTABLE CERVICOGENIC HEADACHE.
A.A. Shakir Medical Dept, Medical College, Erbil, Iraq

AIM: To study the effect of electrical stimulation plus Imipramine and Ibuprofen in patients (Pts) with intractble cervicogenic headache.

METHODS: 108 Pts with non-malignant cervicogenic headache for more than 2 yrs were divided in to 3 groups: A (30)- electrical stimulation (10-24 Volt.Hz. 50) on nucheal region by applying 2 electrodes 25 minutes daily for 6 days; B (38) - Ibuprofen (400mgx3) plus Imipramine (10mgx3) for 3 weeks; and C (40) - electric method for 6 days plus Imipramine and Ibuprofen for 3 weeks.

RESULTS: Pts were painliess or had faint pain during treatment: Group A 70%, Group B 28%, and Group C 90%. Prolonged pain relif lasting for 2-3 months was: Group A 40%, Group B 18%, Group C 88%.

CONCLUSIONS: Several mechanisms may be involved in this long-lasting pain relief: high intensity but tolerable electric current (which differs from TENS), prostaglandin biosynthesis inhibition by Ibuprofen, Imipramine which inhibits reuptake of serotonin and noradrenaline. Nearly 100% of Pts achieved complete pain relief immediatly after electrical stimulation, 70% during treatment; in 40% the pain relif lasted for 2-3 months. This effect may be related to extra-cranial stimulation of periaquductal grey and nucleus raphe magnus region leading to supraspainal inhibition on incoming nociceptive impulse to dorsal horn cells of upper cevical and trigimenal subnucleus caudalis. Prolonged antinociceptive effect of high intensity current may also be related to A fiber stimulation which induces long-term depression of synaptic strength in primary affernet nerve fibers. This form of the afferent induced spinal antinociception does not require activation of GABA, rather activation of the ionotropic and metabotropic glutamate receptors.

TENDER POINTS ARE NOT SITES OF ONGOING INFLAMMATION- IN VIVO EVIDENCE IN PATIENTS WITH CHRONIC TENSION-TYPE HEADACHE
M. Ashina, B. Stallknecht, L. Bendtsen, J.F. Pedersen¹, S. Schifter, H. Galbo, J. Olesen Dept. of Neurology and Danish Headache Center, Glostrup Hospital, DK-2600 Glostrup, Copenhagen, Denmark , Dept. of Medical Physiology and Copenhagen Muscle Research Centre, The Panum Institute and Rigshospitalet, Copenhagen, Denmark

Aim of Investigation: To investigate in vivo concentrations of prostaglandin E2 (PGE2), adenosine 5-triphosphate (ATP), glutamate, bradykinin and other metabolites in a tender point of patients with chronic tension-type headache in the resting state as well as in response to static exercise.

Methods: We recruited 16 patients with chronic tension-type headache and 17 healthy control subjects. Two microdialysis catheters were inserted into the trapezius muscle and dialysates were collected at rest, 15 and 30 minutes after start of static exercise and 15 and 30 minutes after stop of exercise.

Results: There was no difference in resting concentration of inflammatory mediators and metabolites between tender patients and non-tender controls (P > 0.05). We also found no difference in change in interstitial concentration of PGE2, ATP, glutamate, glucose, pyruvate and urea from baseline to exercise and post-exercise periods between patients and controls (P > 0.05).

Conclusions: The present study provides in vivo evidence of normal interstitial levels of inflammatory mediators and metabolites in tender trapezius muscle in patients with chronic tension-type headache both during rest and exercise. Our data suggest that tender points in these patients are not sites of ongoing inflammation.

Acknowledgements: Supported by grants from The Danish Medical Association Research Fund, the Danish Hospital Foundation for Medical Research, the Novo Nordisk Foundation, the Danish National Research Foundation (grant 504-14).

CLINICAL AND EPIDEMIOLOGICAL STUDY ON MIGRAINE OF POPULATION SUFFERING FROM CHERNOBYL DISASTER IN BELARUS
H.I. Navumava, A.D. Navumov, O.I. Klimonenkova Neuroendocrinology, Radiation Medicine, Vitebsk, Belarus , Neuroendocrinology, Radiation Medicine, Vitebsk, Belarus , Neuroendocrinology, Radiation Medicine, Vitebsk, Belarus

Aim of Investigation: To carry out a clinical and epidemiological studies on migraine in populations of Belarus checking out the epidemiological hypothesis concerning the action of low dose radiation exposure.

Methods: We performed a population-based case ascertainment of all available sources of medical care. In addition 263 teenager girls at the age of 15-18 years old were examined with the help of: EEG; EMG; blood concentration of the hormones was measured after each four hours at the lutein, follicular and periovulatory phases by Radioimmune Assay.

Results: Prevalence rate of migraine among people suffering from Chernobyl disaster in 1987 - 2000 varied from 24,000 to 12,000 per 100,000 of population.

Menstrual migraine was the predominated form.

We also found some circadian rhythm of prolactine disorders in the periovulatory period in girls who obtained more than 1.0 Gy on the thyroid and the increase of testosterone baseline in girls living in the area contaminated with radionuclides more than 370 kBq/m2.

The amplitude of generated cutaneogalvanic potentials was higher and the period of latency was longer in girls who obtained more than 1.0 Gy on the thyroid.

Then we have investigated blood ability to transport estradiol and have noticed free estradiol concentration increased in girls who obtained more than 1.0 Gy on the thyroid (5.9+-0.3%). This fact was experimentally confirmed in animals (11.6+-1.7% and 35.9+-7.5%).

Conclusion: Increased incidence of menstrual migraine in teenager girls, victims of Chernobyl disaster, may be explained by a modification of the system of neuroendocrin regulation.

EPIDEMIOLOGICAL AND CLINICAL FEATURES IN CLUSTER HEADACHE IN THE FIRST FRENCH EMERGENCY HEADACHE CENTER
L.G. Benoist, M. El Amrani, A. Ducros, L. Ben Slamia, C. Roos¹, R. Djomby, V. Domigo, L. Morin, V. Besanon, M. Bousser, D. Valade Emergency Headache Center, Lariboisiere Hospital, Paris, France , Neurology, Lariboisiere Hospital, Paris, France

Aim of investigation: To determine the clinical and epidemiological features of a population suffering from cluster headache (CH) and other vascular headaches (OH) at emergency department.

Methods: Complete patient database and diagnosis at discharge were reviewed for the first thirteenth months of activity.

Results: Among 13556 patients, 421 (3.1 %) suffered from typical CH and 0.26 % from OH. Episodic and chronic CH accounted for 42 and 6.2 % respectively. 22.3 % had an undetermined evolution pattern. Atypical forms in regard to I.H.S. were found in 13 %. The male on female ratio was 3.7 in CH against 0.8 in OH. The mean age was 39.5 in CH versus 42. The sex ratio gradually decrease with age until 70. The age of onset was below 40 in 80 % of CH while it was higher in 65 % of OH.

The usual duration of clusters was between 1 and 4 weeks but sometimes reached 16 weeks and more. Most patients had one or two attacks per day but more than 4 in 10.7 %. 82 % were smokers and 12 patients were drug abusers. The CH duration was under 1 year in 17 % but up to 20 years in 13 %. The delay for diagnosis was between 1 and 5 years in one third of sufferers. Preceding diagnosis were: migraine (5.2 %), cranial neuralgias (2.8 %), sinusitis (2.1 %) and dental causes (1 %).

Conclusion:CH remains an underestimated and misdiagnosed cause of headache and is probably more frequent than usually thought. Typical CH has particular features that differs from other types of vascular headaches. I.H.S. criterion may sometimes be to restrictive.

SOCIAL SUPPORT IN THE MANAGEMENT OF MIGRAINE AND CHRONIC DAILY HEADACHE: A QUALITATIVE STUDY
M. Peters, H. Huijer Abu-Saad, V. Vydelingum, A. Dowson, M. Murphy EIHMS, University of Surrey, Guildford, United Kingdom , Kings' Headache Services, Kings' College, London, United Kingdom

Aim of Investigation: To explore the patients strategies for the management of migraine and chronic daily headache (CDH). This abstracts outlines the patients use of social support.

Methods: Thirteen patients (9 women and 4 men, aged 24 to 60), who had suffered from migraine, according to the International Headache Society (IHS) criteria, at one time in their lives, were recruited by theoretical sampling. Semi-structured, individual and tape-recorded interviews (n=13) were carried out and transcribed verbatim. The transcripts were coded and analysed with the assistance of QSR NUD*IST 5 software according to the grounded theory methodology.

Results: At the time of the interview, 7 patients suffered from IHS migraine and 6 patients from CDH (headache frequency >15 days per month). Four themes were identified: family and friends, media, specialist headache groups and informal medical consultations (e.g. nurses, pharmacists). These groups provided a social network that the patients used for support and informal advice to help manage their headaches. Support and information was actively sought by the patients or volunteered by these groups. The support and information obtained influenced the patients decision-making for management and management behaviour.

Conclusions: This study shows that migraine and CDH patients seek information of an informal basis for the management of their condition. It highlights the role of support and advice from a social network that goes beyond formal consultations with a physician.

Acknowledgements: M Peters is a Ph.D. student co-funded by AstraZeneca and the Migraine Action Association (UK).

EXCELLENT PAIN RELIEF IN TENSION HEADACHE WITH SIMPLE HEAD BALANCING, CHIN MUDRA AND APAN VAYU MUDRA - A CLINICAL TRIAL
C.S. Shukla Navajeevan Nursing Home, Jabalpur City, India

AIM OF INVESTIGATION: Drugless approach topain relief in tension headache.

METHODS: Twenty (20) patients were selected. Diagnosis was done with standard parameters with medical, ENT, opthalmic, blood count, and psychoanalysis. All selected patients showed normal investigation but moderate to severe headache. The head balancing was done for 3 days with simple manipulation method. All patients were taught and advised to practice Chin Mudra and Apan Vayu Mudra at home regularly. The follow-up was done after one week. All patients showed remarkable pain relief. Three follow-up were done, after two weeks, six weeks, and 12 weeks.

RESULTS: Eighteeen (18) out of 20 patients remained pain free at the last follow-up. Only 2 patients had intermittent pain which shows poor response to them. The success rate equals 90% which is excellent.

CONCLUSIONS: In considing a drugless approach to pain relief for tension headache, this method of treatment is very simple and effective.

COGNITIVE BEHAVIORAL PREDICTORS AND QUALITY OF LIFE OF MIGRAINE PATIENTS
P. Gupta Pain Management, Vardaan Institute of Mental Health & Pain Management, Lucknow, India

Aim of Investigation : The cost of migraine to individual sufferer is one of the most severe consequences of this condition. Review of literature indicates that cognitive behavioral factors are directly associated with onset of migraine. Quality of life of migraine patients is the focus of contemporary researches. This study explored the quality of life of migraine patients and association of cognitive behavioral factors with onset of migraine.

Methods : 80 male and 80 female migraine patients (age range : 22-46 years with mean age of 32.59 years) where selected for this study who fulfilled the diagnostic criteria of migraine headache proposed by the International Headache Society. These patients did not had any other psychiatric or internistic problems. A control group of 100 normals of the same age range was also selected for this study who had never experienced any psychiatric or internistic problems and they had normal health. PGI Quality of Life Scale, Locus of Control Scale, Optimism Scale and Alienation Scale were administered to these groups individually.

Results : Quality of life of migraine patients was found to be significantly impaired as compared to normal control group. Alienation and pessimism were positively associated with onset of migraine headache.

Conclusions : Results indicate that cognitive behavioral factors are significantly associated with migraine headache and migraine patients need cognitive intervention programme to improve their quality of life.

NEWLY DESIGNED OPEN-END PENCIL POINT SPINAL NEEDLE PROVIDES LOW INCIDENCE OF POSTURAL POSTDURAL PUNCTURE HEADACHE.
S. Hori, Y. Nisimura, H. Nobuhara, Y. Ishibe Anesthesiology, Hakuai Hospital, Yonago, Japan , Anesthesiology, Tottori Univ Fac of Medicine, Yonago, Japan

AIM OF INVESTIGATION: To evaluate effectiveness of the newly designed open-end pencil point spinal needle on incidence of postural postdural puncture headache compared with Quincke type spinal needle.

METHODS: 332 patients (male: 76, female: 256, age: 17-90 yrs, ASA class 1-3) undergoing orthopedic, obsteteric, gynecologic, lower abdominal or urologic surgery were randomly assigned into 3 groups. Spinal anesthesia was performed using new 25G and 23G open-end pencil point spinal needle or 23G Quincke type spinal needle. Lumbar puncture was performed between L3 and L5 with the patient in lateral or sitting position. 2.5-3 ml of isobaric or hyperbaric 0.5% bupivacaine was injected in about 60 seconds. Technical difficulties: number of times to try for dural puncture, rate of change of intervertebral space to puncture, rate of failures, and rate of postoperative headache were documented.

RESULTS: Groups did not differ with respect to demographic data, number of attempts at dural puncture or failure rate. Rate of change of the intervertebral space to puncture was 5.6% in group F-25, 4.0% in group F-23 and 0.8% in group T-23, respectively. Postural postdural puncture headache was seen at 1.9% in group F-25, at 1.0% in group F-23 and at 5.6% in group T-23. Non-postural headache was seen at 3.7% in group F-25, at 1.0% in group F-23 and at 4.8% in group T-23.

CONCLUSION: The newly designed open-end pencil point spinal needle might reduce incidence of postural postdural puncture headache compared with Quincke type spinal needle even if the 23G needle was used. Incidence of postural postdural puncture headache was 1.0%, although this spinal needle might be slightly difficult to puncture.

THE CORRELATION BETWEEN MIGRAINE, HISTAMINE, AND IGE
P. Gazerani, z. Pourpak, A. Ahmadiani Pharmacology, Neuroscience Research center, Tehran, Iran

Aim of Investigation:The physiopathology of migraine is still largely unknown. The possibility of an IgE-mediated allergic mechanism and the role of histamine remains controversial. The aim of present study was the evaluation of serum total IgE and histamine levels in migraine patients and the influence of allergy.

Methods: 70 patients (18-58 years) with migraine without aura were divided in to 2 groups according their history of allergy ( 60% with & 40% without allergy). Serum samples were collected in fasting without allowing any pre medication in 2 conditions of headache and remission periods. There was a control group containing 45 healthy volunteers. Serum total IgE and histamine levels were measured by ELISA and fluorimetric methods respectively.

Results: Serum histamine (ng/ml) and total IgE (IU/ml) levels were found in control group 48.162.70 , 95.015.20 and in migraine with allergy group 184.584.25 , 428.63.22 and in migraine without allergy group 152.483.20 , 146.855.20 respectively.

Conclusions: Total IgE levels in migraine with allergy group were found significantly (P<0.001) above the control and another group suggesting an influence of an IgE-mediated mechanism on migraine. Plasma histamine levels which were significantly elevated (P<0.001) in patients with migraine both during headache and symptom-free periods compared with control group can show although there is an increased susceptibility to histamine in allergic conditions, this molecule has also an unrelated role in migraine.

EFFICACY OF ORAL ELETRIPTAN 40 MG IN PATIENTS WHO PREVIOUSLY DISPLAYED A POOR RESPONSE TO FIORINAL AND/OR FIORICETIN THE TREATMENT OF ACUTE MIGRAINE.
E. Loder , B. Hilliard, K. Taylor Spaulding Rehabilitation Hospital, Boston, MA , Pfizer Pharmaceuticals Group, New York, NY

Aim of Investigation To evaluate the efficacy and acceptability of eletriptan, a potent and selective 5HT_1B/1D agonist effective in treating acute migraine attacks, in patients who had previously responded poorly to Fiorinal and/or Fioricet.

Methods This was a multicenter, 3month, openlabel study of up to 16 migraine attacks in adult subjects (n=160). Oral eletriptan 40 mg was administered at migraine attack onset to patients who had previously not achieved a satisfactory response to Fiorinal and/or Fioricet (or the generic equivalent).

Results One hundred and twentysix subjects completed the study. The overall headache response rate at 2 h was 71%. Headache response was also consistent as 60% of patients achieved a headache response in 71% of their attacks. Overall pain-free response rate at 2 h was 37%. Two hour painrelief rate, defined as an improvement to some relief, a lot of relief, or complete relief, was 74%. Overall functional response rate at 2 h was 69%. Scores for the migrainespecific quality of life (MSQoL) showed significant improvement during the study (P0.001). Patient satisfaction rate with eletriptan 40 mg is high, with subjects reporting being satisfied, very satisfied, or extremely satisfied in 66% of all attacks. There were no treatmentrelated serious adverse events. Most adverse events were mild or moderate in severity and transient in nature.

Conclusions Eletriptan 40 mg is an effective, highly consistent and acceptable treatment for acute migraine headaches in subjects who fail to achieve a satisfactory response with Fiorinal and/or Fioricet.

Acknowledgements: This work was supported by Pfizer.

OCCURRENCE OF HEADACHE IN A WORKING POPULATION
R.I. Raak, A.K. Raak, L. Wahren Medicine and Care, Pharmacology, Linköping, Sweden , Health Department, SAAB Aerospace, Linköping, Sweden

Aim of Investigation: To map the occurrence of headache in relation to working ability and its economic consequences in an employed population.

Methods: The study cohort included 400 subjects who were all employed at a technical industry company in Sweden. Three hundred and fifteen subjects (84% males) answered a questionnaire about the occurrence, duration, severity and treatment of their headache.

Results: Two hundred and two subjects had suffered from headache one time or more during the last three months. The majority (65%) answered that the duration of the headache was between 2 and 24 hours. Five percent had visited the health care system due to severe headache and fifty percent had been working even with severe headache. The latter also scored decreased working ability. The use of pharmacological treatment varied and those not using drugs scored a longer duration of their headache. Experienced stress was scored as the most important factor trigging headache. The economical consequences as a result of decreased working ability and sick listing, in a company with 5000 employees, were calculated to be 3.6 mill. EURO a year.

Conclusions: There is a need to identify, diagnose, treat and evaluate experienced headache in the working population.

Keywords: headache, gender, working ability, economical consequences, occupational medicine.

MIGRAINE IS NOT ASSOCIATED WITH HYPEREXCITABILITY OF THE OCCIPITAL CORTEX. A TRANSCRANIAL MAGNETIC STIMULATION CONTROLLED STUDY
G. Valli, A. Cappellari, S. Zago, A. Ciammola, G. De Benedittis Pain Research & Treatment Unit, Inst. of Neurosurgery, Univ of Milan, Milan, Italy , ² Neurological Clinic, Dept. of Neurological Sciences, Univ of Milan, Milan, Italy

AIM OF INVESTIGATION: Recent studies (Aurora et al., 1998; Afra et al., 1998) have reported that transcranial magnetic stimulation (TMS) of the occipital cortex, in order to detect visual threshold, could be useful in differentiating normal from migrainous patients, thus enabling a better understanding of the pathogenetic mechanisms of migraine in terms of hyper or hypo-excitability of the occipital cortex. However, the results of these studies have been contradictory so far. We therefore wished to evaluate occipital cortex excitability in migraine with and without aura by using TMS.

METHODS: Twenty-two migraineurs (ten with aura and twelve without aura) and sixteen healthy volunteers underwent occipital cortex stimulation by TMS. Subjects wore a blindfold and were asked to report any visual experience (usually phosphenes) during and after stimulation. The stimulator intensity was gradually increased by 10% intervals until a visual experience was reported (stimulation range 0-100%). A variation of the psychophysical method of constant stimuli was used to estimate the absolute threshold.

RESULTS: A mean value of 62.51% was recorded in normal subjects, with a range of 38% to 100%. Migrainous patients reported a mean value of 71.04% (range 44% to 100%) and of 74.21 (range: 46% to 100%) in the migraine with aura and without aura subgroups respectively.

CONCLUSIONS: No significant statistical differences between the three groups were found with regard to visual threshold.Consequently, our TMS study does not confirm hyperexcitability of occipital cortex in migraine as reported in some previous studies.

EFFICACY OF ELETRIPTAN VS NARATRIPTAN FOR THE TREATMENT OF A SINGLE MIGRAINE ATTACK: A MULTICENTER, RANDOMIZED, PLACEBO-CONTROLLED TRIAL
G. Garcia-Ramos, J. Hettiarachchi, B. Hilliard Fundacion Medica Sur, Mexico City, Mexico , Pfizer Pharmaceuticals Group, New York, NY

Aim of Investigation: To compare the efficacy and tolerability of oral eletriptan (40 mg) with oral naratriptan (2.5 mg) and placebo in the acute treatment of migraine.

Methods: Subjects (n=483) were randomized to receive eletriptan (E40, n=192), naratriptan (N2.5, n=199) or placebo (PBO, n=92) in a double-blind, parallel-group study. The primary efficacy endpoint was headache response 2 h after dosing.

Results: Results are presented as eletriptan 40 mg, naratriptan 2.5 mg, and placebo, respectively, with statistical significance given for E40 vs N2.5 or PBO. Eletriptan demonstrated significant improvement in headache response at 2 h (56%, 42% [P0.01], and 31% [P0.0001]), 1 h (34%, 25% [P0.05], and 21% [P0.01]) and also at 4 h (80%, 67% [P0.01] and 44% [P0.0001]). Pain-free response was significantly higher for E40 at 2 h (35%, 18% [P0.0005] and 19% [P0.005]) and 4 h (56%, 41% [P0.01] and 24% [P0.0001]). Sustained relief was greater for patients using eletriptan 40 mg (38%, 27% [P0.05] and 19% [P0.001]). Sustained pain-free response was also improved with eletriptan (22%, 11% [P0.01] and 12% [P0.05]). All causality adverse events (AEs) were generally mild or moderate and transient. Eletriptan had superior patient acceptability (68%, 50% [P0.0005], and 31% [P0.0001]) with significantly more patients rating eletriptan as good, very good, or excellent 24 h post-dose (70%, 53% [P0.0005], and 33% [P0.0001]) compared with naratriptan and placebo.

Conclusions: Eletriptan 40 mg has superior efficacy and high patient acceptability compared with naratriptan 2.5 mg in the acute treatment of migraine.

Acknowledgements: This study was supported by Pfizer, Inc.

ELECTRICAL STIMULATION OF CEREBELLAR FASTIGIAL NUCLEUS TREATMENT AND STUDY OF CGRP AND ET IN MIGRAINE PATIENTS
Y. Mao, X. Wang, H. Lin Dept of Neurology, Shong Shan Hospital, Fu Dan University, Shanghai, China

AIM OF INVESTIGATION: To evaluate the effect of electrical stimulation of cerebellar fastigial nucleus treatment in migraine patients and study the changes of plasma CGRP and Endothelin during and after treatment.

METHODS: 50 migraineurs were studied ( according to IHS criteria). All the patients were stimulated by fastigial nucleus stimulation (FNS) instruments as the only treatment. The therapeutic mode are as follows: Frequency 181%, half an hour every day for ten days. The headache indexes were evaluated and plasma CGRP and ET are measured by RIA before and after treatment.

RESULTS: 46 out of 50 migraine patients have statistically significant reduced headache indexes after treatment (please refer to our previous paper for the calculation of headache indexes) which suggest a good treatment effect. The plasma CGRP decreased from 40.289.27 to 30.219.01 and Endothelium level reduced from 75.5418.90 to 65.7012.31 after treatment.

CONCLUSIONS: The FNS treatment have good effect in prevention of migraine episode related to the reduction of neurotransmitters CGRP and ET. It is worth further studying in the mechanism of FNS stimulation induced CGRP and ET decrease.

ACKNOWLEDGMENTS: Supported by grants of Shanghai Science and Technology Committee. The FNS instruments were provided by Shanghai Ren He Medical Company.

IMMUNOLOCALIZATION OF SEROTONIN RECEPTOR 5HT-1D IN RAT CNS
A.H. Ahn, S. Potrebic, H.L. Fields, A.I. Basbaum Anatomy, University of California San Francisco, San Francisco, CA , Neurology, UCSF, San Francisco, CA , Physiology, UCSF, San Francisco, CA

AIM: The serotonin receptor subtype 5HT-1D is a target of the triptan class of antimigraine drugs and is strongly expressed in a subset of nociceptors in the peripheral nervous system. This study ascertains the localization of 5HT-1D in the central nervous system (CNS).

METHODS: We have prepared an affinity-purified antipeptide antibody in rabbit to a subtype-specific sequence of the rat 5HT-1D receptor for immunolocalization in the rat CNS.

RESULTS: Characterization of a serotonin subtype-selective antibody will be presented. The immunolocalization of 5HT-1D receptor is seen abundantly in the dorsal horn of the spinal cord, corresponding to its expression in small fiber nociceptors of the dorsal root and trigeminal ganglia. Elsewhere in the brain, staining is faint, mainly in the optic and olfactory tracts. Immunolocalization also seen in white matter tracts include the cerebellar hemispheres, entorhinal cortex, and pyramidal tract. Unlike the primary afferents, we did not detect the cells of origin of these fibers and may represent specific axonal localization of the receptor to axons. There may be faint localization in ventral periaquductal structures. We did not detect staining in the raphe as seen by in situ hybridization.

CONCLUSIONS: The immunolocalization of serotonin receptor subtype 5HT-1D shows that it predominates in the central targets of the peripheral nervous system, optic and olfactory tracts. If a 5HT-1D selective agonist were to be shown to work as an antimigraine drug this would have interesting bearing on the "peripheral hypothesis" of migraine.

ACKNOWLEDGEMENTS: Supported by the Howard Hughes Medical Institute and NINDS NS21445 and 14627.

MEMORY FOR PAIN IN PATIENTS WITH DIFFERENT TYPES OF HEADACHE
P. Wang, L. Chow, Y. Chia Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan , Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan , Department of Anesthesiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

Aim of investigation: The results of whether memory for pain in acute and chronic pain had different accuracy have often been contradictory. This study investigated pain memory in chronic daily headache and non-daily headache patients.

Methods: Patients with headache were consecutively recruited from outpatient clinic. The diagnosis of headache was made according to the criteria proposed by International Headache Society. Each participant was asked to complete a daily pain diary for a period of one week. Participants were subsequently asked to recall the avarage, minimum (Min) and maximum (Max) pain they experienced over the period of pain diary.

Result: There were 88 headache patients ( 28 migraine, 17 episodic tension type headache (ETTH), 23 transform migraine (TM), 20 chronic tension type headache (CTTH)) participated in this study. Patients with migraine had the best memory in Min (r=0.64, p=0.032) and Max pain (r=0.64, p=0.024). Patients with TM had the best memory in average (r=0.68, p=0.021) and Min pain (r=0.51, p=0.042). ETTH patient only had fair memory in average, Min and Max pain (r=0.29-0.41). CTTH had better memory in Min pain (r=0.63 p=0.052).

Conclusion: In the more severe episodic headache like migraine, Min and Max pain memory are more accurate. However, in the chronic suffering pain like TM, average pain is better.

Acknowledgment: This study is supported by the National Science Council Taiwan, ROC (NSC89-2314-B-075-181)

INTRAVENOUS VALPROATE IS EFFECTIVE IN THE TREATMENT OF CHRONIC DAILY HEADACHE ASSOCIATED WITH DRUG ABUSE
M. Sorel, J. Saclier A. Simon¹, B. Guillemot², P. Baud Pain Center, Fundation Rothschild, PARIS, France , Pain Unit, Hpital de Nemours, NEMOURS, France

Aim of investigation: a prospective pilot study using IV Valproate(VPA) during inpatients withdrawal.Several reports of IV VPA efficacy for acute migraine¹ and for Chronic daily headache2,3 incite us to test this procedure on 8 consecutive patients during their inpatient drug withdrawal instead of our usual protocol with amitriptylin.

Methods: All patients had a past history of migraine according to the IHS criteria. Drugs abused were triptans or ergotamine. All analgesics and triptans were discontinued. At the beginning of the withdrawal, each patient received the IV preparation of valproate, 7mg/Kg every 8 h during two days and then per os, 750 mg per day.

Results: Six patients were pain free on the third day, 2 patients kept moderate headache and were switched to amitritylin with success, they had recurrent night time headache and a poor sleep. Tolerance to IV and PO VPA was good (one case of nausea). Long time follow-up (6 to 9 months) show a persistent efficiency.

Conclusions: Our results confirm previous reports on IV VPA as a safe, effective and well-tolerated treatment for the overuse analgesics chronic headache. VPA is more rapid acting than Amitriptylin and has a better tolerance. Furthermore, it could be a cost-effective treatment shortening the stay of hospitalisation.

1: Edwards I.H.S. 2001 2: Krusz I.H.S. 2001 3: Sohn I.H.S. 2001

THE EFFICACY OF ELETRIPTAN VS ZOLMITRIPTAN IN THE ACUTE TREATMENT OF MIGRAINE: RESULTS OF A COMPARATIVE, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY
J. Schoenen, T. Steiner, H. Diener, N. Muirhead C. Sikes University Departments of Neurianatomy and Neurology, Liège, Belgium , Imperial College, London, United Kingdom , University of Essen, Essen, Germany , Pfizer Pharmaceuticals group, New York, NY

Aim of Investigation To compare eletriptan 40 mg and 80 mg with zolmitriptan 2.5 mg for efficacy in the treatment of acute migraine attacks.

Methods Subjects (n=1337) were randomized to eletriptan 40 mg (E40; n=392), eletriptan 80 mg (E80; n=396), zolmitriptan 2.5 mg (Z2.5; n=405) or placebo (PBO; n=144) in a double-blind, placebo-controlled, 144-center study.

Results Results are presented for E40, E80, Z2.5 and PBO, respectively. Headache response rates (primary endpoint) were 64%, 74%, 60% and 22% at 2 h (P=0.0001, E80 vs Z2.5) and 28%, 40%, 25% and 5% at 1 h (P<0.0001, E80 vs Z2.5). At both time points E40 and E80 were superior to PBO (P<0.0001, all comparisons). E80 was superior to Z2.5 at 30 min (12% vs 7%; P<0.05). Pain-free rates at 2 h were 32%, 44%, 26% and 6% (P<0.0001, E80 vs Z2.5), and E80 was also superior to Z2.5 at 1 h (12% vs 6%; P<0.005). Sustained response rates (at 24 h) were 44%, 47%, 35% and 11% (P<0.01, E40 vs Z2.5; P<0.001, E80 vs Z2.5; P<0.0001, E40 and E80 vs PBO). E80 was superior to Z2.5 for sustained pain-free rate (29% vs 17%; P<0.0001), relief of nausea at 2 h and functional improvement at 1 and 2 h. The most common adverse events with eletriptan included asthenia, chest pain, nausea and dizziness and were generally mild or moderate. E40 and E80 were significantly more acceptable than Z2.5.

Conclusions Eletriptan 80 mg had greater efficacy than zolmitriptan 2.5 mg in the treatment of acute migraine. Both eletriptan doses were more acceptable to patients than zolmitriptan.

OMINOUS PERIORBITAL PAIN
M.V. Francis, U.S. Nayak Dept of Neuroophthalmology, K V M Hospital and CT Scan Centre, Alappuzha, India

AIM OF INVESTIGATION: To diagnose life and vision threatening periorbital pain without associated inflammatory eye signs presenting to the Neuroophthalmology Department in the coastal district of Alappuzha, South India.

METHODS: 9800 patients were studied over a period of 8 years. Age group: 10 to 80 years. Exclusion criteria -Inflammatory eye signs and fever. Diagnosis was made from a two step approach. Step one - a well taken history, general physical, ocular and neuroocular assessment in all. If step one was suggestive of atypical periorbital pain ( first time sudden onset, progressively increasing, change in pattern, recurrent same site, post traumatic increasing, and any positive neuroocular symptoms or signs)step two was adopted -complete CNS exam, simple lab tests like ESR, other specialty ref and neuroimaging.

RESULTS: Out of 9800 patients, 71 presented with atypical periorbital pain neuroimaging was diagnostic in 31. The lesions were PCA infarcts (4), CP angle tumors (4), Pcom aneurysms (3), Sinovenous thrombosis (3), Benign intracranial hypertension (3), Pit tumors (3), Secondaries (3), Subdural hematomas (2), Sphenoethmoid Mucoceles (2), Trigeminal schwanoma, demyelination, craniopharyngioma, pineal region tumor and Mid-brain cavernoma one each. Giant cell arteritis was diagnosed in 4 patients with markedly raised ESR.

CONCLUSIONS Though migraine origin pain was the commonest cause of periorbital pain in this study (without associated inflammatory eye signs) life and vision threatening pain must not be missed in a busy out patient clinic. Awareness about atypical pain features, neuroimaging and simple lab tests will of great help in saving life and vision of these patients

10th World Congress on Pain, List of topics

10th World Congress on Pain. International Association for the Study of Pain, San Diego, California, USA August 17-22, 2002