10th World Congress on Pain, List of topics

SERTRALIN MONOTHERAPY AND DIABETIC PAINFUL NEUROPATHY
F. Elahi, H. Rafiey, M. Nabavi, N. Saadat, M. Arianpoor, N. Elahi, neurosurgery, jihad, tehran, Iran , ² neurosurgery, shahed university, tehran, Iran , ³ neurology, mostapha khomaini hospital, tehran, Iran , ⁴ endocrinology and internal medicine, imam khomaini hospital, tehran, Iran , ⁵ multidisciplinary pain clinic, ACRCS, tehran, Iran

AIM OF INVESTIGATION: To study prospective long term effect of sertralin on patients with painful diabetic polyneuropathy.

METHODS: A cohort prospective multicentral study with 152 cases of painful diabetic polyneuropathy with at least 6 months follow-up. Patients were followed for 1-3 and 6 months separately.

RESULTS: 16 of them had type 1 diabetes and the rest type 2<NIDDM>. 53% were mail and had a history of 10.63 years of diabetes, varying from 1 year to 32 years. All were categorized as chronic pain and polyneuropathic pain according to clinical and electrodiagnostic findings. Pain decreasing according to numerical analog scale was 35% for the first month of 150 mgs of Sertralin. In this paper you can find much more according to the statistical analysis.

CONCLUSION: Sertralin is safe and seems to be effective in painful diabetic polyneuropathy. For itself it is very challenging; why we choose monotherapy? We advocate no single modality for treatment, because no single modality would be effective.

TREATEMENT OF CHRONIC PAIN SYNDROME WITH VARIOUS ANTIDEPRESSANTS IN PATIENTS WITH THE TERMINAL RENAL DISEASE UNDER CHRONIC HAEMODYALISIS.
N.P. Vanchakova1, K.V. Ignatov, J.D.Psychiatry and Narcology, Pavlov State of Medical, Sanct-Petersburg, Russian Federation

Aim of investigation: To compare effectiveness of the different antidepressants groups for treatment of chronic pain in terminal renal patients.

Methods: McGill pain questionnaire (MPQ), VAS, BPRS-total, GCI scale. 37 out of 80 terminal renal patients had chronic bones pain. 27 patients had the course of therapy with antidepressant: mianserin - 7, tianeptin -10, citalopram -10 patients.10 patients with chronic pain did not have antidepressant therapy (a control group). Antidepressants were administered in average daily doses. Duration of the therapy was 6 week. The study was open and randomized. Index MPQ was 1,41+-0,4, the intensity of pain was 65+-23mm(VAS). The BPRS-scale mark was 27,4+-7,2. The account of the psychical condition by the GCI-scale was 4 (moderate psychical disturbance).

Results: Side- effects observed with all antidepressants were mild. None of the patients refused to continue treatment with antidepressants. After the course of antidepressant therapy index MPQ was: in mianserin used patients 0,6+-0,3, tianeptin 0,83+-0,32 and citalopram 1,2+-0,4. The redaction of the pain level by VAS was: mianserin 31+-14mm; tianeptin 44+-12mm;citalopram 53+-14 mm. The psychical state improved: distinctly (mianserin), moderately (tianeptin), slightly (citalopram) (by GCI-scale). In the control group all indexes did not change.

Conclusion: The mianserin antinoceptive activity was the highest in the observed group.

AMITRIPTYLINE FOR THE TREATMENT OF CHRONIC PAIN IN PERSONS WITH AMPUTATIONS
D.M. Ehde, D.G. Smith, W.T. Edwards, K.M. Campbell1, M.P. Jensen, L.R. Robinson, Rehabilitation Medicine, University of Washington, Seattle, WA , Rehabilitation Medicine, VA Puget Sound Health Care System, Seattle, WA

Aim of Investigation: Tricyclic antidepressant medications are commonly used in treating chronic neuropathic pain, including amputation-related pain. Anecdotal evidence of the analgesic effects of several tricyclic antidepressants exists, but this has not been verified by any randomized controlled trials. This study examined whether amitriptyline, a tricyclic antidepressant, is efficacious in relieving chronic neuropathic pain and improving pain-related physical and psychosocial dysfunction in persons with amputations.

Methods: Thirty-eight participants with chronic phantom and/or residual limb pain were randomized to a 6-week trial of amitriptyline (titrated to a maximum dose of 125 mg/day) or an active placebo, benztropine mesylate (1 mg). Standardized outcome measures of pain intensity, pain interference, depressive symptoms, and disability were administered at pre- and post-treatment by evaluators blind to group assignment. T-tests examined whether there was a medication group effect on the outcome measures.

Results: No significant differences were found between the groups on the outcome variables. Side effects were common and seen as a deterrent to continued use of the active medication.

Conclusions: These findings do not support the use of amitriptyline in the treatment of chronic pain in this population. However, the findings do not rule out the possibility that certain subgroups of persons with acquired amputations may benefit.

Acknowledgements: Supported by grant PO1 HD/NS33988, National Institute of Child Health and Human Development and the National Institute of Neurological Disorders and Stroke.

THE USE OF REBOXETINE IN FIBROMYALGIA AND NEUROPATHIC PAIN; AN OPEN, NON-RANDOMISED,PROSPECTIVE STUDY.
J.J. Browne S. Pain Relief Unit, King's College Hospital, London, United Kingdom

AIM: Reboxetine, a selective noradrenaline reuptake inhibitor, is a relatively new anti-depressant which appears to be particularly beneficial in lethargic depressed patients. The aim of our study was to investigate whether reboxetine is effective in the treatment of neuropathic pain and fibromyalgia (where typically there is a combination of pain and lethargy).

METHODS: This was an open label, non-randomised, prospective study. Patients with fibromyalgia and neuropathic pain were commenced on reboxetine, starting on a dose of 4mgs daily. This could be increased to a maximum of 8mgs. Patients were reviewed at 2, 4, 8 and 12 weeks. Recordings included a visual analogue pain score (VAPS) and a visual analogue fatigue score (VAFS). Initial scores were compared to those at the end of the study period and a reduction of 30% or more was considered clinically significant.

RESULTS: 39 patients were included in the trial, 25 with fibromyalgia and 14 with neuropathic pain. In the fibromyalgia group 8 patients had a significant reduction in VAPS and 9 in VAFS. 9 patients wished to continue taking reboxetine after the trial period ended. In the neuropathic pain group 6 patients had a reduction in VAPS. However only one wished to continue using reboxetine. Apart from lack of efficacy, side effects such as insomnia and agitation discouraged continued use.

CONCLUSIONS: Reboxetine may be useful in the treatment of neuropathic pain and especially fibromyalgia. However, side effects may preclude its use in neuropathic pain at the dosages used in this study. These side effects were not as problematic in fibromyalgia where a feeling of increased energy is typically welcomed.

VENLAFAXINE IN THE TREATMENT OF ATYPICAL FACIAL PAIN
H. Forssell, O. Tenovuo, G. Hampf, E. Kalso, Pain Clinic, Turku Univ Central Hospital, Turku, Finland , Pain Clinic, Helsinki Univ Central Hospital, Helsinki, Finland

Aim of investigation: To study the analgesic effect of venlafaxine in the treatment of atypical facial pain.

Methods: 30 patients suffering from chronic facial pain and who after thorough clinical examinations had received the diagnosis atypical facial pain were recruited. The study was a randomized, double-blind, placebo controlled cross-over study. The two treatments (4 weeks each) were separated by a 2-weeks wash-out period. The dose of venlafaxine was titrated to 75 mg. Pain intensity (VASpi, VRSpi), pain relief (VASpr, VRSpr), and adverse effects were registered on each visit (every two weeks, 6 times). Venous blood samples were collected at the end of each treatment for the determination of the serum levels of venlafaxine and its three metabolites.

Results: Eight patients discontinued because of adverse effects (mainly nausea), two patients because of non-compliance. Of the remaining 20 patients 19 could increase the dose up to 75 mg, one patient remained on 37,5 mg. The median age of the patients was 52 years (range 35-66). The mean duration of pain was 4-5 years.

Baseline pain intensity was 3.8/10. The maximum dose of venlafaxine significantly reduced pain intensity compared with placebo (VASpi;p<0.05, VRSpi;p<0.05). Pain relief was significantly better during venlafaxine treatment compared with placebo (VRSpr; p<0.01).

The mean serum concentrations were: venlafaxine 84 nmol/l, O-demethylvenlafaxine 441 nmol/, N-demethylvenlafaxine 27 nmol/ and N-, O-didemethylvenlafaxine 101 nmol/l.

Conclusions: Venlafaxine effectively alleviated atypical facial pain. However, about every third patient withdrew because of venlafaxine related adverse effects.

DULOXETINE: A POTENTIAL NEW TREATMENT FOR DEPRESSED PATIENTS WITH COMORBID PAIN.
D.J. Goldstein, M.A. Iyengar, S. Detke, M.J. Mallinckrodt, C.H. Lu, Y.Duloxetine Antidepressant Team, Eli Lilly and Company, Indianapolis, IN

Aim of Investigation: Pain is common in patients with major depressive disorder (MDD), but assessment of pain has been neglected in studies of MDD. Serotonin (5-HT) and norepinephrine (NE) are implicated in both MDD pathophysiology and analgesia mediated by descending pain pathways in brain and spinal cord. Duloxetine hydrochloride, a potent and balanced reuptake inhibitor of 5-HT and NE, is efficacious in reducing persistent and neuropathic pain in animal studies at doses consistent with 5-HT and NE reuptake inhibition in vivo. The present study examined the therapeutic efficacy of duloxetine on painful physical symptoms experienced by depressed patients.

Methods: The effect of duloxetine on painful physical symptoms was evaluated in three randomized, double-blind, placebo-controlled studies in outpatients with MDD in which duloxetine demonstrated statistically significant superiority to placebo for improving mood. Visual analog scales were used to assess overall pain severity, time in pain and pain interference with daily activities.

Results: In these trials, duloxetine demonstrated significant superiority over placebo in reducing overall pain severity, as well as other pain measures.

Conclusions: These data suggest that duloxetine, a potent and balanced reuptake inhibitor of 5-HT and NE, is an efficacious new treatment for painful physical symptoms associated with MDD.

Acknowledgements: Eli Lilly and Company funded these studies. All authors are employees of Eli Lilly and Company.

DOES AMITRIPTYLINE BEAR CARDIAC ARYTHMOGENIC POTENTIAL WHEN USED IN PAIN CONTROL ?
M. Lantri-Minet, H. Alchaar, M.A. Merlino, S. Diochot, G. Romey, N. Memran1, M. Lazdunski, M.D. Drici, Pain Department, CHU de Nice, Nice, France , Department of Pharmacology, CHU de Nice, Nice, France , IPMC, CNRS, Sophia-Antipolis, France

AIM OF INVESTIGATION : To evaluate effect of amitriptyline(AMT)on cardiac repolarization during pain control, a stepwise approach was undertaken by i)multiple EKGs in a controlled study with 10 patients receiving increasing doses of i.v. AMT and ii)challenging with AMT the IKr current which represents the main target of drugs prolonging cardiac repolarization.

METHODS : The main endpoints were i) clinical: the AMT-induced increase of the QT interval corrected (QTc)with Bazett's formula at the end of the perfusion (100 mg) on Day 4 as compared to pretreatment, ii)experimental: the potency (IC50) of AMT in blocking IKr tail currents in HERG assay.

RESULTS : The QTc prolongs significantly (+ 38 23 ms, p<0.05). Despite an extremely tight monitoring, the QTc remains highly variable, due to the correction of a significant increase of the heart rate (by 10 bpm, representing 15 to 20%, n= 10) subsequent to AMT. The AMT challenge of IKr current, as recapitulated in COS cells by HERG transfection, efficiently permits to ascribe this variable effect to a significant blockade of the potassium current IKr (IC50 ~ 3 M) which controls the cardiac repolarization.

CONCLUSION : As for iv-AMT in pain control, drug potential to affect the cardiac repolarization and prolong the QT interval duration is better assessed by the HERG assay in mammalian cells. This is especially true when drugs which block IKr bear ancillary properties susceptible to interfere with QT measurement, by modulating the heart rate like AMT.

ACKNOWLEDGMENTS : PHRC Program funding

ANALGESICS AND ANTIDEPRESSANT TREATMENT IN ACUTE HERPES ZOSTER
K. Keskinbora,^, I. Pekel, F.,Anesthesiology, Pain, Istanbul, Turkey

Aim of investigation: To determine the effects of pre-emptive treatment of postherpetic neuralgia (PHN) with antidepressant drugs.

Methods: We studied 33 patients, aged 50-84 (mean 66.5), with acute herpes zoster (AHZ) of 1 month (3-28, mean 12 days) duration. They had taken antiviral therapy. We treated them with tramadol (100-400 mg/day) and paracetamol (2000 mg/day) as analgesic and tricyclic antidepressant or selective serotonine re-uptake inhibitors as antidepressant (amytriptiline 50-100 mg/day < 60 age >citalopram 20 mg/day). Assesment (A) of these drugs are done before treatment (A0), at the 4 week (A4) and 8 week (A8) by using a 10 cm. visual analog scale (VAS) and Beck depression inventory (A=VAS/Beck). At the end of 4 week, if VAS<4 analgesics used were stopped but antidepressant was continued to use. Pain persisted over 8 weeks accepted as PHN.

Results : As followings: A0: 8.2/20.7, A4: 3.5/6.5, A8: 1.39/11.08. In fourteen patients(46.6%), effective analgesia was reached at 4 weeks. Remaining patients were continued to take analgesics and antidepressant. After 8 weeks, only 6 patients have been suffering from pain .

Conclusion: By means of our protocol, ratio of PHN is very low ( 18 %) in this age group. What are the factors : Analgesics in acute phase, or antidepressant agent, or synergistic effect of combination of these agents? Which factor is more efficient of?

Also correlable decrease in Beck may results from treatment of depression secondary to pain by our treatment regimen or treatment of masked depression caused by stressful event usually seen in patients just before herpes zoster disease.

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