THE ANALGESIC EFFICACY OF LAMOTRIGINE IN CENTRAL POST-STROKE PAIN.
Grethe Andersen'. Karsten Vestergaard2, Bo T. Kristensen2, Hanne Gottrup', Troels S. Jensen', Dept of Neurology, Aarhus Univ Hospital' and Dept of Neurology, Aalborg Hospital2, 9000 Aalborg, Denmark
Aim of Investigation: To study the pain relieving effect ofLamo-trigine in central post stroke pain (CPSP). Methods: The design was a randomised, double-blind, placebo-controlled 8 week cross-over study with Lamotrigine in increasing doses to 200 mg once a day for two weeks. The treatment periods were separated by a 2 week wash-out. The primary effect parameter was patients diary scores of pain at 6 p.m. on a visual analog scale (VAS: 0-10). The median score from the last week of each treatment period on 200 mg Lamotrigine or placebo was compared. Secondary end-points were: 1) global pain scores on the SF-36 questionnaire and 2) pain intensity (VAS) following: elec-trical toothbrush for 60 seconds and von Frey hair 1.5 x pain threshold and 3) the concomitant use of Paracetamol. Further, the area of spontaneous pain was assessed and the pain intensity (VAS) following an acetone droplet was scored.
Results: 31 patients suffering from an ischaemic stroke and CPSP for more than 3 months were included between 1 September 1997 and 1 January 1999. 19 patients have completed the study and 6 patients have, so far, dropped out due to side-effects or protocol violation. The final results of the trial will be presented.
Acknowledgment: The study was supported by the Glaxo Welcome Company.
EFFECTS OF INTRAVENOUS LIDOCAINE IN CENTRAL PAIN: A DOUBLE-BLIND PLACEBO CONTROLLED STUDY.
N. Attal'. L. Brasseur', F. Guirimand', M. Dupuy', V. Godet', F. Parker2, M. Chauvin', D. Bouhassira''3. "Centre d'Evaluation et de Traitement de la Douleur, Hopital Ambroise Pare, Boulogne; Service de Neurochirurgie, le Kremlin Bicetre; 'INSERM U-161, Paris, France.
Aim of Investigation: Systemic local anaesthetics can significantly reduce pain due to peripheral neuropathy. In the present study the efficacy of systemic lidocaine was evaluated in a double blind placebo-controlled and cross over fashion in 16 patients with central pain due to stroke (n = 6) or spinal cord injury (n = 10).
Methods: Lidocaine (5 mg/kg) or saline were administered intrave-nously (over 30 minutes) at 3 weeks interval. Spontaneous pain and brush-evoked tactile allodynia were rated using a VAS scale before injection and every 15 minutes during 120 minutes after the end of administration. Quantitative sensory testing was performed before injection and immediately after the injection. Von Frey hairs and a thermotest device were used to determine the mechanical- and thermal-, detection and pain thresholds. The responses elicited by suprathreshold thermal (heat and cold) and mechanical stimuli were measured on a VAS, to evaluate hyperalgesia. Measurements were performed in the area of maximal pain and in a homologous non-painful area.
Results: Lidocaine was significantly superior to placebo in reducing ongoing pain intensity and brush-induced allodynia up to 60 and 45 minutes respectively after the injection. Mechanical and thermal detection thresholds were not significantly modified. Lidocaine significantly reduced mechanical hyperalgesia, but was not superior to placebo on thermal heat/cold pain thresholds and thermal hyperalgesia.
Conclusion: Systemic lidocaine significantly reduces spontaneous pain and mechanical allodynia/hyperalgesia due to CNS injury. However, the duration of the analgesia does not seem to outlast the half-life of the drug.
DIAGNOSIS AND TREATMENT OF MYOFASC1AL PAIN SYNDROME |MPS] IN PATIENTS WITH MYELO-PATHIC PAIN
HCE Barrero, TY Lin, ERL Dobbro, LA Rogano, MJ Teixeira. ACF Sousa, Pain Clinic, Univ ofSao Paulo Medical School, R. Conselheiro Brotero, 1539, cj 12, Cep 01232-010 Sao Paulo, Brazil.
Aim of Investigation: The evaluation of the occurrence ofMPS and of its role in suffering in patients presenting myelopathic pain.
Methods: One hundred and fifty one patients (67.8% male) presenting myelopathic pain were evaluated. Complete clinical, physi-atric and neurologic examinations were performed. Deafferent-ation, musculo-skeletal, psychosomatic and visceral components of pain were searched. Special attention was directed to the identification of the myofascial latent or active trigger points [TPs]. All patients were treated with analgesics, anticonvulsants and psycho-tropics and followed a multidisciplinary rehabilitation program. Abnormal postures and reasons for overload of musculo-skeletal structures were also analyzed. Those presenting MPS were teached about posture and kinesiotherapy. When necessary, acupuncture, TPs infiltration, and/or physical therapies were performed.
Results: Twenty eight percent of patients presented significant MPS as an aggravating factor of pain complaints. Eighty one percent of them had 75% or more improvement of the original pain after readaptation of posture and habits and kinesiotherapy. In 9% of them, other rehabilitative methods resulted in additional alleviation of pain.
Conclusions: MPSs are frequent in patients presenting myelopathic pains. The treatment of MPSs is an important tool for improvement of quality of life and of the suffering in these cases.
PAIN FOLLOWING SPINAL CORD INJURY: FACTORS RELATED TO PROLONGED PAIN EXPERIENCE AND UNSUCCESSFUL PAIN MANAGEMENT
Carole Bishop. Ph.D. Vancouver General Hospital, Psychology Dept and Spinal Program, VHHSC, #416-2775 Heather St, Vancouver, B.C. V5Z 1M9
Aim of Investigation: Adequate pain management is a significant problem in acute and post-acute recovery stages of Spinal Cord Injury (SCI). Central/ neuropathic pain experience is a distressing, often late-onset risk factor for increased rehabilitation stay and emotional distress. Factors associated with the development, lengthy experience, and poor management of SCI pain is relatively unexplored. Aim is twofold: to determine the relation between known risk factors for pain managment difficulties on SCI post-acute subjective pain experience, and to determine the relation between risk factors and development and intractability of central pain.
Method: Subjects included consecutive trauma-related SCI admissions to acute SCI unit between 1996 and 1998 (n=150) with ASIA A, B, C or D diagnoses. Study data obtained from normal procedural reports and medical chart information. Measures included:VAS pain ratings, premorbid substance abuse (SA), psychiatric diagnoses, number of days on daily narcotic medication, presence and treatment of central pain. Hospital Ethical Approval submitted.
Results: Main variable of interest is subjective pain intensity (Visual Analogue Scale; VAS, "0" to "10") ratings at one and four days post-admit, and weekly thereafter to discharge. Association of pain intensity to variables ofSA, psychiatric history, pain medication protocol will be delineated for Ss, with, and without, central pain development. Secondary examination of spinal diagnoses (lesion type/level, intervention) and demographic variables (e.g., age, gender) will also be examined for predictive power.
Conclusions: Selected factors associated with pain management and development of central pain should be delineated within a diverse SCI population.
REBOXETINE, A SELECTIVE NOREPINEPHRINE REUPTAKE BLOCKER, IS INEFFECTIVE FOR CENTRAL PAIN
Vincenze Bonicaizi, Sergio Canavero. Pain Relief Unit, Dept. Neu-rosci., Molinette Hospital, Turin, Italy. Aim of Investigation: To confirm that norepinephrine is the key molecule involved in antidepressant analgesia in a human chronic pain model.
Methods: 6 patients, 4 men and 2 women, suffering central pain, were administered single-blindly, reboxetine, a highly selective norepinephrine reuptake blocker, up to 10 mg PO, if tolerated, over two weeks.
Results: Only one patient with brain central pain reported more than 50% pain relief. Interestingly, this patient was worsened by all previous treatments. All other patients reported 0 to 25% relief and these were deemed failures. The only significant side effect was urinary retention in two cases, with no history ofprostatic problems.
Conclusions: In this small trial, reboxetine did not afford significant benefit for central pain. Previous studies found that mixed norepinephrine/serotonin reuptake blockers (e.g. amitryptiline), but not serotonin reuptake blockers relieved neurogenic pain, pointing to norepinephrine as the key playei. Our study suggests that this is not the case, and that both these transmitters (and perhaps others) are important in antidepressant action on neurogenic pain.
SOME POPULATION DATA ABOUT CENTRAL POST-STROKE PAIN.
David Bowsher. Pain Research Inst, Rice Lane, Liverpool L25 7XE, U.K.
Aim of Investigation: To determine the extent of the occurrence of central post-stroke pain in persons surviving to the age of 80.
Method: 1071 elderly survivors (537 female) with a median age of 84 (range 69-107) from the randomised pool set up by the Institute of Human Ageing, Dept. of Psychiatry, Univ of Liverpool, were questioned about stroke and pain by trained observers.
Results: 72 subjects (2/3 male) had had completed strokes, at a median age of 74. Eight of them (5 male) complained of pain deemed to be of central type. Onset was immediate in 6 cases; only two described their pain as burning. The proportion of stroke subjects with CPSP (11%) was higher than the proportion with multi-infarct dementia (7%).
Conclusions: (i) Since the present figures represent only 80+-year-old survivors, the real prevalence of CPSP in the whole population must be considerably higher than this. Even 11% would yield a UK prevalence of some 70,000 individuals. Andersen et al's1 prospective study in a younger population yielded a lower prevalence (8%). (li) The mean age is much higher, and the prevalence
of burning pain lower, than in a large hospital-referred group2, implying that (a) burning pain is commoner in younger patients, and should not be regarded as a necessary criterion of central pain, and (b) a large proportion of elderly CPSP patients are not being referred to pain clinics, and may not be being adequately treated.
Acknowledgments: The UK NHS considers the occurrence of CPSP to be "too rare" to warrant funding; this work was supported by the Pain Relief Foundation.
QUANTITATIVE SENSORY TESTING IN PATIENTS WITH PAINFUL OR PAINLESS SYRINGOMYE-L1A: A PROSPECTIVE STUDY.
L. Brasseur'. N. Altai', F. Parker2, M. Tadie2, M. Chauvin', D. Bouhassira''3. 'Centre d'Evaluation et de Traitement de la Douleur, Hopital Ambroise Pare, Boulogne; Service de Neurochirurgie, le Kremlin-Bicetre; ^INSERM U-161, Paris, France.
Aim of Investigation: Few systematic studies have quantitatively evaluated pain and sensory deficits in syringomyelia. The present prospective study aimed to perform quantitative sensory testing (QST) in patients with painful or painless syringomyelia before and after surgical treatment of their synnx (at 3 and 9 months). Methods: Consecutive patients with cervical or dorso-lumbar syringomyelia completed the study and underwent surgery. Most patients had central neuropathic pain. Spontaneous pain and brush-evoked allodynia were assessed. Von Frey hairs, vibrameter and a thermotest device were used to determine the mechanical-, vibratory-, thermal-detection thresholds, and the mechanical and thermal pain thresholds.
Results: Deficit in temperature and pain sensibility was evidenced in all cases and deficit in vibration and touch sensibility in 2/3 of cases. Magnetic resonance scan, including axial images, showed good correlation between paramedian extension of the syrinx and thermal deficits. The magnitude of the thermal and tactile deficits was similar between areas of spontaneous pain and adjacent non-painful areas. Spontaneous pain was generally located within an area of thermal deficit, but its intensity was not correlated with the magnitude of the deficit. Surgery induced a significant decrease of the deficits (tactile more than thermal). Effects on neuropathic pain were variable and not correlated with the effects on thermal sensibility.
Conclusion: These results confirm that QST are useful in clinical practice in patients with syringomyelia, and allow some hypotheses about the mechanisms of neuropathic pain in these patients.
THALAMOCORT1CAL DISINHIB1TION IN A CASE OF CENTRAL PAIN: A P.E.T. STUDY
Kenneth L. Casey. Donna Cross*, Thomas J. Morrow, and Satoshi Minoshima*, Neurology Research, VA Medical Center, and Div.of Nuclear Medicine and Dept. of Physiology, Univ of Michigan, Ann Arbor, Michigan, USA 48109
Clinical history and examination. Three years ago, this 67 year-old hypertensive right-handed man experienced the sudden onset of constant, persistent, painful dysesthesiae of the left hemibody and face. Sensory examination is normal except for deep pressure allodynia on the left (L/R: 2.1/4.3 Kg; p < 0.001) and elevated but symmetrical cutaneous heat pain thresholds (L/R: 49.4/50.1°C). MRJ shows a 2 x 4 x 7.5mm lacunar infarction in the lateral right ventral posterior lateral (VPL) thalamus.
Positron emission tomography. Twenty-one 3D H; 0 scans were performed during 7 conditions: 49,52, and 55 °C during (Imin) repetitive, spatially randomized, 5sec contact stimulation of each volar forearm followed by a rest (no stimulation) scan. Average VAS ratings of heat intensity (0-10; 5 = pain threshold) were symmetrical at 49 (R/L: 3.7/3.3) through 55 (R/L: 8.4/8.5). Volumes of interest (4.5mm radius spheres) were established bilaterally within the VPL and insular cortex. At rest, estimated regional cerebral blood flow (rCBF) was markedly reduced on the right (%R < L: VPL, 7.9; insula, 17.4). However, heat stimulation (49-55 °C) of either side showed exaggerated rCBF increases relative to rest on the right (% increase: RVPL, 4.6; LVPL, 1.5; R insula, 1.5; L insula, - 3.4; p< 0.04).
Conclusions. The reduced background thalamocortical activity reflects reduced inhibitory control of the remaining thalamocortical neurons, causing constant pain and exaggerated excitatory responses to stimulation. Supported by VA Ment Review and NIH grant P01 HD 33986.
CHRONIC PAIN FOLLOWING SPINAL CORD INJURY.
Ruth Defrin', Avi Ohri2 and Gideon Urea', Dept. of Physiology and Pharmacology, Sackler School of Medicine, Tel Aviv Univ, Israel' Sheba Medical Center, Tel-Hashomer, Israel2.
Introduction: The pathophysiology of chronic central pain following spinal cord injury (SCI) is unclear. Two main hypotheses based on few and mainly uncontrolled, descriptive investigations have been proposed. One suggests that the chronic pain is a result of lesion of the Dorsal columns (DC). The other suggests that lesion of the Spinothalamic tracts (STT) is the underlying mechanism.
Aim of Investigation: To test these hypotheses using controlled quantified somatosensory testing in SCI subjects with (SC1P) and without (SCINP) chronic pain.
Methods: Sensory testing was conducted below the level of lesion. The threshold for warmth (WS), cold (CS) and heat-pain (HP) sensations were used to test STT function. Light touch, graphaesthesia and the identification of speed of movement of touch stimuli on the skin were used to test DC function. The presence of Wind-up like pain, Allodynia and Hyperpathia was also assessed.
Results: Both SC1P and SCINP exhibited a marked reduction in thermal and tactile sensibility below the lesion compared to normal values (e.g., mean threshold for WS, CS and HP of 42.4, 12.5 and 48.8°C compared to 35.9, 28.5 and 42.4°C respectively) with no significant difference between the groups. However SC1P exhibited loss of thermal quality to heat stimuli 3 times more often compared to SCINP (pO.01). Chronic pain in SC1P was only present in skin areas with reduced or absent thermal sensibility whereas painfree areas below the lesion in these subjects were normal. Allodynia was present only in SC1P. Wind-up like pain and hyperpathia were significantly more common in SC1P compared to SCINP (73.3 and 87% compared to 14 and 28%) and were present only in the pain areas.
Conclusions: A STT but not DC lesion is a necessary condition for the occurrence of chronic pain following SCI however not a sufficient one. It is probable that a critical level of STT lesion is needed to induce the chronic pain. The presence of Wind-up, Hyperpathia and Allodynia in the pain areas of SC1P indicates a state of hyper-sensitivity. The combination of sensory loss together with abnormally evoked pain characterizes painful skin areas also in peripheral neuropathies. This suggests that peripheral and central pain might share common mechanisms underlying their emergence.
ELECTROCONVULS1VE THERAPY FOR CENTRAL POSTS-TROKE PAIN.
Nagafumi Doi*'. Mitsuru Nakamura*', Kunihiro Isse*', Takehiko Nagao*2 Hitoshi Mera*3, Akihiro Oikawa*4, Shizuo Takeyama*3, Takaomi Taira4 (SPON: T.Taira) Dept.of Psychiatry', Neurology2 and Anesthesiology3, Tokyo Metropolitan Ebara General Hospital Dept. of Neurosurgery4, Tokyo Women's Medical College
Background: Central post-stroke pain often resists every treatment, causing suppression of activities of daily living and depression in some of those patients. Electroconvulsive therapy (ECT), which is well established to have therapeutic effects on depression, has been reported to reduce intolerable pain associated with depression. Based on the experience that ECT relieved pain and allodynia due to putaminal hemorrhage in a patient with depression, we applied ECT to patients with central post-stroke pain.
Subjects and Method: Subjects were 12 patients with central post-stroke pain (5 cases with suprathalamic lesion and 7 cases with thalamic lesion). Based on the written consent from the patients, a course of bilateral ECT (110V for 5 sec, 6 to 12 sessions with interval of 1 to 7 days) was performed. Local cerebral blood flow (CBF) was studied by single photon emission computed tomography (SPECT), using """Tc-ECD about 1 week before and after a course of ECT.
Results: Complete relief of pain and allodynia was obtained in the cases with suprathalamic lesion and partial relief in the other cases. Hypoperfusion was observed in the thalamus contralateral to the site of pain before ECT. After ECT, the local CBF of the contralateral thalamus was improved to the level ofipsilateral one in the cases with suprathalamic lesion. In 9 patients, pain recurred after three months or later. However, a better and more long-standing effects were obtained after second course of ECT.
Conclusion: ECT relieves or reduces the pain and allodynia in central post-stroke pain through the improvement of thalamic function.
A POSTAL SURVEY OF PAIN AND DYSESTHESIAS IN PATIENTS WITH SPINAL CORD DAMAGE.
N.B. Finncrup. F.W. Bach, I.L. Johannesen*, T.S. Jensen. Dept of Neurology and Danish Pain Research Center, Univ Hospital of Aarhus, DK-8000, Denmark
Aim of Investigation: To study the prevalence and character of pain and dysesthesias in patients with spinal cord damage.
Methods: A questionnaire was developed and mailed to all 434 outpatients at the rehabilitation centre for spinal cord damaged patients in Western Denmark covering a population of 2.5 million inhabitants.
Results: By Jan 5th 241 questionnaires were returned, 168 M and 73 F, median age 40.6 years, range 19 to 80. Median time since spinal damage was 9.0 years. The aetiology was traumatic spinal cord injury in 80% of cases. The spinal injury level was cervical in 36%, thoracic in 35%, lumbar in 27% and diffuse in 1%. 191 patients (79%) reported pain or dysesthesia (P/D) with a median intensity of 46 (VAS 0-100). P/D was reported by 46% of patients above lesion and by 68% at or below lesion. At or below lesion P/D was constant in 40% and occurred daily in 33%. 60% reported superficial pain, 82% deep pain, 35% abdominal pain, and 37% painful spasms. 43% were treated by analgesics at the time of survey. Stress or anxiety (reported by 41%), tiredness (37%), cold (29%), and weather change (27%) were most frequently identified as aggravating circumstances. 60% reported that P/D could be evoked by non-noxious stimulation of the skin (30% reported pain by touch, 26% by cold and 14% by warm).
Conclusion: The postal survey indicates: Pain occurred in 79% of patients, the median pain intensity was 46 (VAS) and Allodynia occurred in 60% of patients.
LASER EVOKED POTENTIAL CORRELATES OF CENTRAL PAIN RELIEF UNDER GABAPENTIN.
Jurgen Lorenz'. Helge Beck2, Hartmut Burkle2, Manfred Wcst-phal3, 'Inst Physiology, Dept Anesthesiology, 'Dept Neurosurgery, Univ Hosp Eppendorf, Martinistr 52, D-20246 Hamburg, Germany.
Aim of Investigation: To study efficacy ofgabapentin on central pain and experimental pain in a patient with multiple hemangio-blastosis (Hipple-Lindau syndrome).
Patient and Methods: A 46-ys-old patient suffered cramp-like pain in the right foot, that first appeared after surgical removal ofahe-mangioblastoma at the vermis cerebelli related to Hipple-Lindau disease. Loss of vibration sense and pathological tibial nerve SEP P40 suggested a dorsal column/lemniscal lesion. Systemic NSAIDs, carbamazepin and opioids, as well as lumbar sympathetic block failed to achieve pain relief. Diagnostic intrathecal administration of local anaesthetics at Thi 1/12 resulted in complete sensory-motor block below Th8 and disappearance of pain. Systemic gabapentin was given up to 1800 mg/day. Pain was scored on a 10-cm VAS. Amplitudes of laser evoked brain potentials (LEP) were measured before and during treatment. Tones presented 3 s after laser stimuli served to control vigilance by auditory evoked potentials (AEP).
Results: 1800 mg/day ofgabapentin reduced pain from VAS 9 to 4. Walking distance and night sleep improved significantly. Before medication, laser stimulation of the affected limb revealed abnormal C-fiber related ultralate LEPs at the presence of normal AS-fiber related late LEPs. Late and ultralate LEP amplitudes decreased dose-dependently, whereas AEP amplitudes remained constant.
Conclusions: The lemniscal lesion, either caused during surgery or by a new hemangioma manifestation might have disinhibited impulses from the medial pain system mainly supplied by peripheral C-fibers. This may have resulted in central pain and abnormal elicitation of ultralate LEPs. Reduced amplitudes of late and ultralate LEPs and clinical pain relief at the presence of unchanged AEPs under gabapentin suggest antinociceptive and de-facilitative actions without global CNS-depression.
LOCATION, QUALITY AND INTENSITY OF PAIN FOLLOWING SPINAL CORD INJURY (SC1) RELATIONSHIPS WITH OTHER CLINICAL ASPECTS
Eva Widerstrom-Noga. Emesto Felipe-Cuervo*, Robert P. Yezier-ski, The Miami Project to Cure Paralysis, Dept of Neurological Surgery, Univ of Miami School of Medicine, Miami, FL 33136, USA
Aim of Investigation: To describe SCI pain with respect to location, quality and intensity and to explore relationships between these factors and other characteristics of pain following SCI.
Methods: Two-hundred-and-seventeen individuals out of 330 with SCI (65.8%) volunteered to fill out a structured pain anamnesis concerning characteristics of their pain.
Results: Chronic pain was represented over the entire body, although the back area was the most common location indicated by 61.8% of the subjects. The location of pain was associated with certain qualities of pain, i.e., subjects marking pain in the neck-shoulder and back region, reported significantly more "aching pain", whereas individuals marking pain in the upper extremities, chest, stomach, buttocks and lower extremities reported significantly more "burning pain". While the average VAS pain intensity rating was 5.5 ± 11.8, subjects indicating pain in the lower extremities, reported significantly higher pain intensities than subjects not marking these areas. Pain in the upper extremities, neck and shoulder and also pain of "aching" quality, were more frequently reported by tetraplegics than paraplegics.
Conclusions: The clinical presentation of pain following SCI is confusing because of different pathophysiological pain-producing mechanisms. The description of location, quality and intensity of pain is important and can be helpful in differentiating between nociceptive and neuropathic pain. Exploring the relationships between these and other clinical aspects of SCI pain may advance the development of individually designed treatment strategies.
Acknowledgments: This work was supported by The Miami Project and the State of Florida.
ACUTE PAIN IN HERPES ZOSTER
Robert H. Dworkin, Robert W. Johnson, David R.J. Griffin,* Dept ofAnesthesiology, Univ of Rochester School of Medicine and Dentistry, 601 Elmwood Ave, Box 604, Rochester, NY 14642, USA
Aim of Investigation: To investigate the relationships between acute pain in herpes zoster and age, sex, rash seventy, dermatome, and presence of a painful or dysesthetic prodrome.
Methods: Two indepedent samples of herpes zoster patients participating in clinical trials of famciclovir vs. acyclovir (N=545) and famciclovir vs. placebo (N=419) were evaluated within 72 hours of rash onset before beginning treatment. Results: In both samples of patients, greater age, greater rash severity, and presence of a prodrome predicted greater acute pain severity. In multiple regression analyses, these variables were independently associated with greater acute pain severity. In addition, in both samples of patients, female sex and trigeminal zoster were each significantly associated with less severe rash.
Conclusions: Previous studies have demonstrated that greater age, greater rash severity, and presence of a prodrome in acute herpes zoster patients are risk factors for postherpetic neuralgia (PHN). The results of this study demonstrate that these three risk factors for PHN are also associated with greater pain severity at the beginning of the acute herpes zoster infection. Herpes zoster patients who are older, who have had a prodrome, or who have a more severe rash should therefore be targeted for treatment of acute pain as well as for interventions designed to prevent PHN.
Acknowledgments: Data collection was sponsored-by SmithKline Beecham Pharmaceuticals.
ACYCLOVIR AND CONTINUOUS EPIDURAL INFUSION THERAPY (CEIT) IN AHZ PAIN, AND THE INCIDENCE OF PHN
Koichiro Hori, Kenjiro Dan, Kazuhiko Hirata, Haruhiko Manabe, Kazuo Higa, Dept ofAnesthesiology, School of Medicine, Fu-kuoka Univ, Fukuoka, 814-0180, Japan
Aim of Investigation: Persistence of acute herpetic pain (AHP) which is started to treat within 2 weeks after eruption, was evaluated with age, acute pain severity, and severity of eruption, during and after acyclovir and CEIT treatment.
Subject and Method: Subjects were 53 inpatients with acute herpetic pain, ages mean 63.9 (22-91). Acyclovir 500 mg was given intravenously a day for 5 days (21 cases) or 4 g/day for 7 days orally (30 cases). All patients (graded in 3 pain groups; VAS>70mm 18, 69>VAS>50mm 27, VAS<50mm 8, and eruption was divided in 3 groups; severe eruption patients 27, moderate eruption 19, and mild eruption 7) received continuous epidural infusion with 0.5% bupivacaine 0.3-0.7 ml/hr for 2-4 weeks. Pain was assessed by Visual Analog Scale (VAS) in every day during admission days.
Results and Conclusions: 49 cases with AHZ pain were controlled under 10 mm of VAS value within 2-6 weeks. Four patients with AHP, however, have been developed into PHN. Age of PHN patients were 78, 76, 75, 72 years old with all severe eruptions and severe pain (maximum VAS 65-100 mm). Two cases with acyclovir was given intravenously and the other 2 cases 1 g/day for 7 days orally or none because of renal failure. Our results suggested that 1) Age, severity of acute pain and seventy of eruption is useful as the oredictive factors of PHN. 2) Oral acvclovir within 72 hours after eruption is advisable, 3) Oral acyclovir and CEIT shortens the acute pain duration and protects incidence ofPHN.
CAPSAICIN FOR TREATMENT OF POST-HERPETIC NEURALGIA (PHN). A DOUBLE BLIND-CROSSED STUDY
M. Okada. M.J. Teixeira, S.Tengan, P.M. Mchendon, M. Hisano, B. Boguchwal, Pain Clinic, Univ of Sao Paulo Medical School, Rua. Conselheiro Brotero 1539, cj 12, Cep 01232-010, Sao Paulo -Brazil
Aim of Investigation: Double blind evaluation of the efficacy of topical capsaicin (Pharmacia in Vitro®, Sao Paulo, Brazil) for treatment of PHN.
Methods: 19 patients (mean = Ply old, 63% female) presenting long-lasting PHN (median = 2 m) affecting dorsal dermatomes (14), trigeminal nerve (3), and cervical dermatomes (2) were treated with topical application of 0.025% capsaicin or placebo during 6 weeks, accordingly to a prospective double blind study. VAS, daily life activities (DLA), McGill Pain Questionnaire (MPQ), and psychological evaluation were quantified.
Results: The mean previous VAS was 7.0 and became 5.5 in the treated patients and was 7.0 and became 7.1 in the placebo patients. VAS reduced in 56.3% of the capsaicin patients and increased in 6.3%. VAS reduced in 43.8% and increased in 12.5% of the placebo patients. MPQ descriptors reduced in 40% and increased in 33.3%; MPQ indexes reduced in 65% and increased in 25% of in capsaicin patients. MPQ descriptors reduced in 33.3% and increased in 46.7%; MPQ indexes reduced in 31.3% and increased in 56.3% of the placebo patients. DLA improved in 40.0% and got worse in 25.0% of the capsaicin patients. DLA improved in 23.1% and got worse in 61.5% of the patients.
Conclusion: Topical capsaicin is an effective agent for treatment of PHN.
CHRONIC SECONDARY HYPERALGESIA IN SOME PHN PATIENTS: RESULTS OF CAPSAICIN APPLICATION VERIFIED BY SKIN BIOPSY
Rowbotham MC. Petersen K.L, Sandroni P*, Friedman E*, Cluff R*, Brennum J*, Fields HL, UCSF Pain Clinical Research Center, Univ of California, San Francisco, CA 94115, USA.
Aim of Investigation: Determine ifallodynia associated with 'irritable nociceptors' in PHN represents chronic secondary hyperalge-sia
Methods: The most painful area (MPA), the area ofallodynia (ALLO), and 6 testing sites (each 9cm2) were marked. Sites A,B were in MPA. Site C was in ALLO, but outside MPA. Site D was outside ALLO in 'normal' skin a dermatome above or below. Sites E,F were in skin contralateral to MPA. Thermal sensory testing and rating ofallodynia-severity was performed in all sites. Capsaicin 0.075% was applied for 90 minutes, first on unaffected Site F and later on Site A. Changes in pain, allodynia, and area ofallodynia were rated, 3mm punch-biopsies were carried out at Sites B,C,D,E and stained with the axonal marker PGP-9.5. A ' capsaicin-re-sponder' was defined as showing reduced tolerance of capsaicin in MPA, increased PHN-pain and allodynia, and expansion ofallodynia area.
Results: 17 subjects with thoracic PHN participated. None used medicated topical therapies. Capsaicin was not painful in normal skin. The 5 'capsaicin-responders' fit the 'irritable nociceptor' type of PHN with significantly more background pain and allodynia and preserved sensory function compared to the non-responders. In 3 capsaicin-responders, allodynia expanded into Site D which had cutaneous nerve fiber density and thermal sensation identical to unaffected contralateral skin.
Conclusions: Capsaicin activation of'irritable' c-nociceptors increased PHN-pain and allodynia. The expansion of the area ofallodynia into previously non-painful skin that had normal sensory function and cutaneous innervation can be interpreted as a demonstration of secondary hyperalgesia in chronic neuropathic pain.
Acknowledgments: Supported by NINDS 21445 and the Danish Research Counsil.
GABAPENTIN FOR THE RELIEF OF POST-HERPETIC NEURALGIA.
Sabato A.F.. Zucchi R*, Serafini G., Gatti A., Fumarola E., Univ of Tor Vergata Rome, Dept. Of Surgery, Pain Clinic, *Inst. I.D.I.., IRCCS, Rome
Aim of Investigation: The present open study aimed to address the efficacy of the anticonvulsivant drug, gabapentin, on post-herpetic neuralgia (PHN).
Methods: Twenty-seven consecutive patients 8F/19M (mean age: 70 years), suffering from PHN (duration of pain: median 25.30 months) were included. All patients had been unsuccessfully treated, previously, with different analgesic drugs. Gabapentin was initiated gradually up to 900-1200/ day. Systemic evaluation was conducted, using VAS, at inclusion and 3 months later. Tactile allodynia was evaluated with a brush. At inclusion patient reported spontaneous pain with a mean VAS 7.11± 0.70, and 85% had tactile allodynia. VAS at 3 months was 5.48 ± 5.65.
Results: Three patients reported an important global improvement and 10 patients a moderate global improvement. Side effects were all minor and mainly consisted of fatigue and sonnolence.
Conclusion: Gabapentin appears to be an effective treatment of PHN in 48.14% of patients.
EFFECTS OF GABAPENTIN (NEURONTIN*) ON PAIN QUALITY IN PATIENTS WITH POST-HERPETIC NEURALGIA (PHN)
Brett Stacey. Michael Rowbotham, Norman Harden, Leslie Magnus-Miller*, Paula Bernstein*, Oregon Health Sciences Univ., Portland, OR, Univ. of California, San Francisco, CA, Rehabilitation Inst of Chicago, Chicago, IL, Parke-Davis Division ofWamer Lambert, Moms Plains, NJ 07950, USA
Aim of Investigation: To examine the effect of gabapentin (GBP, Neurontin*) on pain quality in subjects with PHN in addition to assessing the effect of GBP on pain reduction.
Methods: This double-blind, placebo-controlled parallel-group study enrolled subjects (N=229) with symptoms of PHN for more than three months after healing of a zoster skin rash, a score of ?40 mm on the Visual Analog Scale (VAS) of the Short Form McGill Pain Questionnaire (SF-MPQ) at screening and randomization, and an average Daily Pain Score of>4 during the 7 day screening phase. Following screening, subjects were randomized to receive GBP or placebo (PBO) during the 8-week treatment phase. In the first 4 weeks of treatment, GBP was increased to a target dose of 3600 mg/day, or the maximum tolerated dosage; in the second 4 weeks, dosage was to remain constant. Pain descriptions were evaluated based on the 15 items descriptive of pain on the patient-rated SF-MPQ completed at screening, baseline. Weeks 2, 4 and 8. Pain ratings occurred at regular intervals over the course of the trial.
Results: The mean changes from baseline in total score, sensory score (11 items) and affective score (4 items) of the SF-MPQ were evaluated. The results of each analysis indicated a statistically significant change for the GBP group as compared to the PBO group (PO.001). As new analyses, within the sensory category, the descriptors throbbing, shooting and heavy showed a significant change (P<0.05) from baseline to endpoint (Week 8) in the GBP group but not in the PBO group. All descriptors in the affective category (tiring, sickening, fearful, punishing-cruel) showed a significant change from baseline to endpoint in the GBP group but not in the PBO group. Subjects receiving GBP had a statistically significant reduction in average daily pain score from 6.3 to 4.2 points compared with a change from 6.5 to 6.0 in subjects receiving PBO (PO.001).
Conclusion: GBP has demonstrated effectiveness on several specific descriptors ofPHN pain quality in addition to providing significant pain relief.
Acknowledgments: Supported by Parke-Davis Division ofWamer Lambert Co. Dr. Magnus-Miller and Ms. Bernstein are employees of Parke-Davis and own stock and hold options to purchase further stock in the company.
AXONAL FLOW INHIBITORS FOR TREATMENT OF POSTHERPET1C NEURALGIC
P. Stump. M.J.Teixeira, T.Y.Lin, M. Okada, E. Sow, Pain Clinic, Univ of Sao Paulo Medical School, Rua. Conselheiro Brotero 1539, cj 12, Cep 01232-010, Sao Paulo - Brazil
Aim of Investigation: Evaluation of the treatment ofpostherpetic neuralgic (PHN) with Vincristine and Doxorubicine.
Methods: 44 patients presenting PHN not relieved with conventional treatments with psychotropics, anticonvulsants and capsaisin were selected for regional application of Vincristine or radicular infiltration with Doxorubicine. VAS, daily life activities and sensory abnormalities were evaluated. VAS ranged from 6 to 10 (mean 8.5). 14 underwent iontophoretic application of 0.01% Vincristine (mean = 32 sessions), 6 intradermal mesotherapy application of 0.05% Vincristine (mean = 5 sessions), and 24 percutaneous radicular infiltration of 0.1% Doxorubicine (mean = 1 session).
Results: There was alleviation or significant reduction ofallodynia and improvement of the functionality of the effected areas in 8/14 patients treated with Vincristine iontophoresis, in 4/6 cases treated with Vincristine mesotherapy, and in 18/24 cases treated with Doxorubicine. The mean VAS after the procedures became 4. 60% of the patients had 50% or more improvement of the original pain. The follow-up period ranged from 5 to 16 months.
Conclusion: Axon flow blockers are potentially effective agents for treatment of PHN.
METADON FOR TREATMENT OF POSTHERPET1C NEURALGIA (PHN). A DOUBLE BLIND-CROSSED STUDY
S. Tengan. M. Okada, M.J. Teixeira, R.A.A.Oliveira, Pain Clinic, Univ of Sao Paulo Medical School, Rua Conselheiro Brotero 1539, cj 12, Cep 01232-010, Sao Paulo - Brazil
Aim of Investigation: Double blind evaluation of the metadon in treatment of PHN.
Methods: 10 patients (mean = Ply old, 60% female) presenting long-lasting PHN (median=41m) affecting dorsal dermatomes (4), trigeminal nerve (3), and cervical dermatomes (3) were treated with metadon 2.5mg t.i.d. or placebo during 3 weeks, accordingly to a prospective double blind-crossed study. Physical, neurological and psychiatric evaluations were made in all cases. VAS, daily life activities (DLA), and McGill Pain Questionnaire (MPQ) were quantified.
Results: The mean previous VAS was 8.0 and became 7.0 in the metadon patients and was 7.2 and became 7.6 in the placebo patients. MPQ descriptors reduced in 83% of metadon and in 60% placebo of patients. DLA did not change in both groups. No side effects were observed.
Conclusion: 5mg/day of metadon was not very effective for treatment of PHN. Higher doses of metadon should be tried in these cases.
PATIENT-CONTROLLED EPIDURAL ANALGES1A (PCEA) FOR OUTPATIENTS WITH INTRACTABLE HER-PETIC NEURALGIA
Yu-Chuan Tsai. Han-Ping Chen, Fu-Chi Kang, Tsung-Ying Chen, Section of Pain Management, Dept ofAnesthesiology, NCK.UH, Tainan, Taiwan
Aim of Investigation: To investigate the outcome and effects of PCEA with low-dose bupivacaine infusion in patients with intractable herpetic neuralgia as home therapy.
Methods: Five patients were referred to our pain clinic because of the failure of standard therapy for severe herpes neuralgia over thoracic area. After getting approval, epidural catheter was inserted. Effects were confirmed with 1 % lidocaine 8 ml in divided doses. A patient-controlled analgesia (PCA) pump (Baxter AP I) was installed, filled with bupivacaine 0.0825 or 0.1%, and set by the following orders: basal rate of 1.5 to 2.5 ml/hr, PCA dose 1.5 to 2.5 ml, lockout interval 15 or 20 min, and a one hour dose limit of 6 or 8 ml. Patients were phoned at home everyday. The pump was refilled, the wound was managed every 3 days, and the catheter was replaced every 7 to 10 days. Basal rate was reduced and discontinued when no PCA dose was required.
Results: The interval between zoster onset and PCEA application ranged from 27 to 60 days (mean 35.6). The duration using PCEA was from 10 to 28 days (mean 17.6). All treatments resulted in effective and satisfactory pain relief (VAS 10 to 0-3), with increase of physical activities to usual levels and release of sleep and appetite disturbance. No dele- terious effects were found. One patient developed tolerance effect of bupivacaine. Conclusions: PCEA with low-dose bupivacaine infusion can provide patients with intractable herpetic neuralgia a feasible, safe, and effective treatment modality with limited side effects at home.
PAIN AND UNPLEASANT SENSATIONS AFTER BREAST SURGERY: A RETROSPECTIVE STUDY OF 46 WOMEN
Keiko Yamanouchi'. Masaki Kitahara", Eisuke Fukuma6*, Akito Ohmura2 Dept ofAnesthesiology'and General Surgery1', Teikyo Univ Hospital Mizonokuchi, Kawasaki, Kanagawa, 213-8507 JAPAN
Aim of Investigation: Post mastectomy pain syndrome influenced quality of life after breast surgery significantly. Although the incidence of the post mastectomy pain syndrome was reported 4~20% in women who underwent breast surgery in the USA, no clinical studies had ever been done in Japan.
Methods: We sent questionnaire to 46 women who underwent breast surgery in our hospital between February 1996 and October 1997 to investigate its incidence and characters.
Results: 43 (93.5%) patients returned the questionnaire. The age of the patient was 36~82 years old (54 y.o. on average). The types of the surgery were breast conservative surgery 20 (46.5%), total mastectomy 12 (27.9%), modified radical mastectomy 9 (20.9%), radical mastectomy 1 (2.3%), and partial mastectomy 1 (2.3%). The number of the patients who complained of some unpleasant sensations in the axilla, breast, chest, and/or upper arm was 33 (76.7%). These sensations included tightening 24 (55.8%), pares-thesia 19 (44.2%), aching 14 (32.6%), numbness 13 (30.2%), pain 12 (27.9%), fatigue 8 (18.6%) and hyperesthesia 3 (7.0%). The incidence of pain was higher in the patients who underwent the surgery within one year (44%) than those more than one year (16%) ago. 11 (33.3%) patients reported that they wanted some treatment.
Conclusion: In our cross-sectional retrospective study, incidence of the post mastectomy pain was 27.9%, which was higher than the results of other studies. However, a series of prospective studies are necessary to investigate incidence and characters of the post mastectomy pain syndrome as well as to determine the efficacy of medical interventions.
PATTERNS OF SENSORY CHANGE IN WOMEN FOLLOWING AXILLO-MAMMARY SURGERY
Jackie Cooper*'. Lesley Bromley' and Andrew Baranowski2, Depts of 'Academic Anaesthetics and ^am Management, Room 103, 1s1 floor crosspiece, Middlesex Hospital, Mortimer St, London WIN 8AA, UK.
Aim: To investigate sensory changes in women, with and without non-acute pain, following axillo-mammary surgery for breast carcinoma.
Methods: 36 women, who had had breast surgery and an axillary clearance more than 3 months previously and 11 healthy volunteers underwent sensory testing, including: threshold to touch using Von Frey hairs, thresholds to perception of hot and cold, vibration sensation and pressure. The antero-medial aspect of the upper arm and the anterior chest wall were both tested bilaterally.
Results: Patients with no pain or numbness after surgery had sensory testing thresholds that did not differ significantly from women who had not had surgery. Nerve damage in the form of numbness was detected in 15 patients. One third of these also had pain, but this was not consistently characterisable by sensory testing.
Conclusions: There are a variety of causes of pain after axillo-mammary surgery: this is not a homogeneous group. Many patients have nerve injury, demonstrated by the presence of numbness, however most of these women do not have pain. It is also common to have pain without any evidence of nerve injury on sensory testing. In the patients with pain there were no consistent sensory changes in any of the modalities that we measured. We were unable to detect any selective damage to any particular nerve fibre types. Only one patient gave a history suggesting neuropathic-type pain. She had a reduced threshold to deep pressure, but no differences in vibration sense or hot-cold limen. Most pain following this type of surgery is not neuropathic.
9th WORLD CONGRESS ON PAIN, 1999, Vienna, Austria, p.434 - 440
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