PAIN IN MULTIPLE SCLEROSIS PATIENTS BOL KOD OBOLJELIH OD MULTIPLE SKLEROZE
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1 ORIGINAL ARTICLE UDC: PAIN IN MULTIPLE SCLEROSIS PATIENTS BOL KOD OBOLJELIH OD MULTIPLE SKLEROZE Sanja Grgić 1, Aleksandra Dominović- Kovačević 1, Zoran Vukojević 1, Duško Račić 1 Abstract: The aim of this section study is to determine prevalence of pain based on its type, intensity, quality, pain location, therapy treatment, and the impact it makes on multiple sclerosis (MS) patient s everyday activities. Besides pain characteristics, demographic and clinical parameters have been also analyzed. The study included 87 patients diagnosed with definite MS according to McDonald s criteria, ranging in age from 17 to 6, EDSS below 8., and with absence of relapse. Excluding criteria were: disease exacerbation during previous month period, chronicle diseases, psychiatric diseases previously verified, and corticosteroid therapy in the course of the previous month period The research made use of the following scales: Expanded Disability Status Scale (EDSS) and Visual Analog Scale (VAS) for assessment of intensity of the pain. Results indicated high prevalence of pain in MS patients, from 6.9% to 87.4%, depending on the type of pain. In patients with pain the most frequent was intermittent neuropathic pain of 77%. Most frequently the pain was felt in legs, 47.8%. VAS medium score was 3.9+/-SD2.6%. A group representing 36.2% of patients stated that the pain interfered moderately with their everyday activities, and 33.3% of patients stated that the pain interfered severely with their everyday activities. Patients mostly take medicaments for pain once or few times a month (43, 2%). Special efforts should be directed to discovery and treatment of the pain, which would result in better forecast and quality of life. Key words: pain, prevalence, multiple sclerosis Sažetak: Cilj ove studije presjeka je određivanje prevalencije bola prema tipu, intenziteta, kvaliteta, lokacije bola, terapijskog tretmana, i utjecaja na svakodnevne aktivnosti kod bolesnika sa multiplom sklerozom(ms). Pored karakteristika bola analizirani su demografski i klinički parametri. U studiju je uključeno 87 bolesnika sa definitivnom dijagnozom MS postavljenom prema Mc Donaldovim kriterijumima, uzrasta od 17-6 godina, EDSS ispod 8. i u odsustvu relapsa. Kriterijumi za isključenje su bili: egzacerbacija bolesti u poslednjih mjesec dana, hronične bolesti, ra 1 nije verifikovana psihijatrijska obolenja, te kortikosteroidna terapija u poslednjih mjesec dana. U ovom istraživanju korišćene su sledeće skale: Proširena skala funkcionalne onesposobljenosti (EDSS) i Vizuelna analogna skala za procjenu intenziteta bola (VAS). Rezultati pokazuju da bol ima visoku prevalenciju kod bolesnika sa MS, od 6,9% do 87, 4%, zavisno od tipa bola. Kod bolesnika sa bolom najčeši je intermitentni neuropatski bol 77%. Bol se najčešće javlja u predjelu nogu 47,8%, a najrjeđe u predjelu grudnog koša i lica 5, 8%. Srednji skor VAS je 3, 9+/- SD2,6. U studiji se 36, 2 % bolesnika izjasnilo da bol osrednje remeti svakodnevne aktivnosti, a 33,3% se 1 Clinic of Neurology, Clinical Centre Banja Luka, Republika Srpska, Bosnia and Herzegovina *Correspondence to: Sanja Grgić, MD, MSc,, Address: Voždovačka 2.,78 Banja Luka, Republika Srpska, Bosnia and Herzegovina, grgic@teol.net Received: Accepted: Financial disclosure: nothing to report 14 Curr Top Neurol Psychiatr Relat Discip. Vol XIX No. 3-4, September-December 211
2 izjasnilo da bol dosta remeti svakodnevne aktivnosti. Bolesnici najčešće uzimaju jednom ili nekoliko puta mjesečno lijekove za bol (43, 2%). Posebne napore je neophodno uložiti u otkrivanje i liječenje bola koji bi rezultirali boljom prognozom i kvalitetom života. Ključne riječi: bol, prevalencija, multipla skleroza INTRODUCTION Frequently pain is an early and initial MS symptom, which could disable patients in their daily activities. The pain, as a sensor symptom directly related to damage of nerve conductivity or CNS demyelization, is defined as a central neuropathic pain. This individual symptom can be described only by a person experiencing it (1, 2, 3). In various studies different methods for MS pain classification were used. In some of them definition of the pain is based on its location, mechanism (muscle spasm, central pain, etc.) and duration as paroxysmal or chronicle pain (4, 5). Back in 28 O Connor et al. suggested the latest MS pain classification (6) (Table 1): Type of Pain Continuous central neuropatic pain Intermitent central neuropatic pain Muscular-skeletal pain Mixed pain Headache Table 1: MS pain classification Example Limb dysesthetic pain Lhermitte s sign, trigeminal neuralgia Painful tonic spasms, backache, muscular spasms Intensity of the pain in MS patients is described in numerous studies. It is mostly defined by patient s personal assessment of pain intensity on the scale from to 1, where = no pain, and 1 = unbearable pain (Numerical Rating Scale) or by Visual Analogue Scale (VAS), which are also the most frequently used scales for evaluation of pain intensity. Average pain intensity on numerical rating scale ranges from 4.8 to 5.8. Patient s pain anamnesis is taken, i.e. the patient describes the pain and the location of the pain occurrence. Based on such obtained data the pain location and quality are determined. The Short Form (36) Health Survey (SF-36) scale is the scale used to determine the impact of disease made on the quality of life, and we have used it to demonstrate influence of the pain, as a significant MS symptom, on daily activities, and consequently on the quality of life. More recent studies have shown large impairment of life quality by MS patients pain suffered (7, 8). It is important to treat the pain based on its type and cause. The treatment includes medicaments, behavioral therapy, physical treatment, and in some cases surgery. The pain is a complex symptom frequently requiring multi-disciplinary treatment, and involvement of pain treatment experts (9, 1). Aims of the study: to determine prevalence of pain based on pain type, intensity, location, quality, therapy treatment, as well as to determine pain interference with MS patients daily activities. MATERIALS AND METHODS This section study included 87 MS patients completely meeting all criteria required chosen out from 2 originally selected patients. Inclusion study criteria were: definite MS diagnose according to McDonald s criteria (11, 12, 13), age from 17 to 6, EDSS below 8., with absence of relapse. Exclusion study criteria were: disease exacerbation during previous month period, chronic dis- Curr Top Neurol Psychiatr Relat Discip. Vol XIX, No. 3-4, September-December
3 eases, psychiatric diseases previously verified, and corticosteroid therapy in the course of the previous month period. A questionnaire composed of two parts was used in the study. The first part of the questionnaire was used to determine MS patients demographic and clinical characteristics. The second part of the questionnaire covered characteristics of the pain, such as presence of the following: pain in the moment of the interview, chronicle painful symptoms, periodical painful symptoms, painful syndrome, sudden occurrence of pain, location of pain, pain intensity, pain influence of daily activities, type of sensitive and painful symptoms, taking medicaments during painful episodes, frequency of taking medicaments. The following scales were used in the study to examine MS patients single functions: Expanded Disability Status Scale (EDSS) and Visual Analog Scale (VAS) for assessment of intensity of the pain. Results obtained by means of statistical analysis are presented numerically and shown as both table and graph. RESULTS Demographic characteristics obtained by the study showed that out of the total of 87 MS patients there were men (M) and 57 women (W). The ratio M: W = 1: 1.9. In the moment of the study examination the patients average age was 37.7 years +/- SD 1.2, where the youngest patient was 17, and the oldest one 59. The average number of years spent in school was 12.2 years +/-SD 2.2, where the least number of years was 3, and the largest one 18. The majority of patients had completed secondary school. Clinical characteristics obtained by the study showed that average age at the beginning of the disease was.1 +/-SD 9.3 years. The youngest age at which the disease appeared in the population examined was 15, while the oldest age was 46 years. Based on the development of the disease the largest number of patients had relapse-remittent forms of MS (77%) in relationship to secondary progressive (17.2%) and primary progressive (5.7%) form of MS. Distribution of MS patients related to EDSS showed the largest number of patients ranged from EDSS=2. to EDSS=4., that is moderate functional disability. MS patients medium EDSS score value was 3.1 +/-SD 1.4, where the minimum was 1. and maximum 7.. Results for the period of MS duration in patients examined showed that average disease duration was 7.2 +/-SD 6.1 years, where the shortest period of duration was 1 year, and the longest 34 years. Prevalence of pain in the moment of examination of MS patients was 6.9%. Prevalence of chronic pain in the MS patients examined was 62.1%. Prevalence of periodical pain in the same group was 87.4%, and prevalence of painful symptoms in those MS patients was 78.2%. Prevalence of sudden pain in MS patients examined was 64% (Figure 1). Figure 1. Prevalence of pain in MS patients based on type of pain ,9% 62,1% 87,4% 78,2% 64,% Instantaneous Chronic Intermittent At any time Sudden No pain With pain 16 Curr Top Neurol Psychiatr Relat Discip. Vol XIX No. 3-4, September-December 211
4 Based on the most recent classification of pain in MS patients, prevalence of intermittent neuropathic pain in MS patients is 77%, prevalence of continuous neuropathic pain in MS patients is 55.2%, prevalence of muscular-skeletal pain is 36.8%, and prevalence of mixed pain is 18.4% (Table 2). Type of Pain Number of Patients Prevalence (%) Intermitent neuropatic pain Continuous neuropatic pain Muscular-skeletal pain Mixed pain Table 2. Prevalence of pain in MS patients based on type of pain. Pain was most frequent in legs and least frequent in thorax and facial area (Figure 2) ,8 23,2 27, ,8 1,1 5,8 8,7 1,1 11,6 Head Face Neck Thorax Back Arms Hands Legs Feet Figure 2. Prevalence of pain in MS patients based on type of pain. The largest number of MS patients stated to feel strong and very strong pain (Figure 3) ,8 % ,4% 5,8% 11,6% 17,4% VAS Very weak Weak Medium Strong Very strong Figure 3. Intensity of pain in MS patients. Curr Top Neurol Psychiatr Relat Discip. Vol XIX, No. 3-4, September-December
5 Medium score of Visual Analogue Scale (-1) was 3.9+/-SD 2.6, the lowest score was., the highest score was 9., and median was 5. (Table 3). Influence of pain on MS patients daily activities was significant and in the study 36.2% of patients stated that pain interfered with their daily activities on a medium level, 33.3% of patients stated that the interference was quite present, 17.3% of patients stated that their daily activities were obviously impeded, 11.6% of patients stated that interference of pain was on a low level, and 1.4% of patients stated that they felt no influence of pain on their daily activities (Figure 4). Variable Score Medium Score 3.9 Standard Variation 2.6 Median 5. The Lowest Score. The Highest Score 9. Table 3. Visual Analogue Scale (-1) for assessment of pain intensity in MS patients. 36,2% 33,3% 2 11,6% 17,3% 1 1,4% Not at all Little Medium Quite Obviously Figure 4. Influence of pain on MS patients daily activities Analyzing use of medicaments taken to relieve the pain in MS patients the following results were obtained: analgesics are used by 37 patients (45.7%), antidepressants by 5 patients (6.2%), antiepileptic drugs by 6 patients (7.4%), and antispastic drugs by 2 patients (2.5%). Most frequently patients used analgesics to relieve the pain in MS, and least frequently antispastic drugs were used. MS patients examined mostly take pain relieving medicaments once or few times a month (43.2%), then once or few times a week (29.6%), once or few times a day (17.3%), and 8.6% of patients take medicaments constantly, while 1.2% of patients never use medicaments. DISCUSSION Prevalence of chronic pain in the population of MS patients examined in our study was 62.1% (Figure 1) (14). In 27 study Khan et al (15) examined chronic pain in MS patients prevalence of chronic pain was 65%. The study examined characteristics of chronic pain, disabilities caused by the pain, pain treatment, and impact on the quality of life. The study results comply with results obtained in our study. Prevalence of pain in the moment of examination was 6.9% (Figure 1). In 24 Solari et al. (5, 6) studied pain prevalence in the moment of examination of MS patients. That was a multicentre study with a direct interview including 1672 patients. According to the study pain prevalence in the moment of examination of MS patients was 43%. In 28 O Connor et al. (6) published systemized and summarized results of all their up to then studies of pain in MS. Results summarized from 18 Curr Top Neurol Psychiatr Relat Discip. Vol XIX No. 3-4, September-December 211
6 their 21 studies of prevalence of pain in MS patients showed that the prevalence ranged from 29% to 86%, which corresponds to results in our study. Based on examination of hypotheses and identification of pain mechanism in MS patients O Connor et al proposed a new classification of pain: 1. continuous central neuropathic pain; 2. intermittent central neuropathic pain; 3. musculoskeletal pain; and 4. Mixed neuropathic and nonneuropathic pain. Based on the most recently recommended classification of pain (6), our study has shown that the prevalence of intermittent neuropathic pain in MS patients is 77.%, prevalence of continuous neuropathic pain 55.2%, prevalence of muscular-skeletal pain 36.8%, and prevalence of mixed pain 18.4% (Table 2). Results of examination of MS patients pain distribution based on localization showed that in 47.8% of patients the pain occurred in legs, in 27.5% in back, and the least frequently, in thorax, 5.8%, and in facial area, 5.8% (Figure 2). Localization of pain most frequently mentioned by literature is in lower extremities and back. In a pattern of MS patients with pain Svendsen et al. (16) had 58% of patients with central neuropathic pain. The most frequent localizations of pain were legs (96%), back (7%), and arms (52%). Results from our study showed that pain intensity determined by Visual Analogue Scale (VAS) in the population examined was the following: 63.8% of patients had strong, 17.4% very strong, and only 1.4% very weak pain (Figure 3). Two more recent studies had the following results: 58% of patients stated to feel strong pain, and 15% stated to feel very strong pain, which are approximate values of our results (17, 18). Medium score of visual analogue scale is 3.9+/-2.6, the lowest score is., the highest score is 9., and median is 5. (Table 3). Intensity of pain in MS patients has been described in numerous studies. In four studies intensity of pain in MS patients was measured by means of numerical scale of -1 and their results ranged from 4.8 to 5.8 which is approximately what we have obtained as results in our study. Examination of influence of pain on MS patients daily activities in our study showed that 36.2% of MS patients had the pain impeding their daily activities on a medium level, and 33.3% had the pain considerably impeding their daily activities, while only 1.4% of patients did not have any pain at all impeding their daily activities (Figure 4). Literature states that the pain impedes daily activities in 42% of MS patients. Pain in MS patients decreases the quality of life including decreased physical and emotional functioning (7, 19). Examining use of medicaments to relieve the pain in MS patients we have obtained results showing patients most frequently, 45.7%, used analgesics, and least frequently spasmolytics, 2.5%. The largest number of pain relieving medicaments were taken one or few times a month, 43.2%, and once or few times a week 29.6%, while only 1.2% of patients never used such medication. In the study by Hadjimichael et al (2) results obtained showed only 2/3 of MS patients used analgesics. Similar results were published indicating that frequency of use of pain relieving therapy ranged from 22% to 54% (6, 21, 22). Taking into consideration modest knowledge about MS patients pain treatment, new investigations should be directed to efficiency and safety of existing treatments of neuropathic and non-neuropathic pain in MS patients including antidepressants, anticonvulsive medicaments, ophiodic analgesics, and non-steroid anti-inflammatory medicaments. CONCLUSION This section study has shown that pain has a high prevalence in MS patients decreasing significantly their participation in daily activities. Taking into consideration that the pain is a symptom often not recognized and neglected in MS patients, it frequently remains without a serious therapy treatment. Up to now treatment of MS patients has implied alleviation of physical disablement by a symptomatic therapy in phase of acute relapse and application of immunomodulatory medicaments, which contributed to long lasting duration of disease. Special efforts should be made in discovering the pain and improving its treatment which would result in better prognosis and course of the disease, as well as better quality of life. This study Curr Top Neurol Psychiatr Relat Discip. Vol XIX, No. 3-4, September-December
7 pointed out the significance of further investigation of the pain, as well as correlation with clinical parameters, and depression and fatigue in MS patients. REFERENCES 1. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG. Multiple Sclerosis. N Engl J 2; 343: Pekmezovic T, Jarebanski M, Drulovic J, Stojisavljevic N, Levic Z. Prevalence of multiple sclerosis in the Belgrade, Yugoslavia. Acta Neurol Scand 21; 14: Rosati G. The prevalence of multiple sclerosis in the world: an update. Neurol Sci 21; 22: Svendsen KB, Jensen TS, Overvard K, Hansen HJ, Koch-Hendricksen N, Bach FW. Pain in patients with multiple sclerosis: a populationbased study. Arch Neurol 23;6: Osterberg A, Boivie J, Thuomas KA. Central pain in multiple sclerosis: prevalence and clinical characteristics. Eur J Pain 25;9: O Connor AB, Schwid SR, Hermann DN, Markman JD, Dworkin RH. Pain associated with multiple sclerosis : Systemic review and proposed classification. Pain 28;137: Kalia LV, O Connor PW. Severity of chronic pain and its realtioship to quality of life in multiple sclerosis. Mult Scler 25;11: Benito-Leon J, Morales JM, Rivera-Navarro A, Mitchell AJ. A review about the impact of multiple sclerosis on health-related quality of life. Disabil Rehabil 23; 25: Finnerup NB, Otto M, Jesen TS, Sindrup SH. Algormithm for neuropathic pain treatment: an evidence based proposal. Pain 25;118: Hooge JP, Redekop WK. Trigeminal neuralgia in multiple sclerosis. Neurology 1995;45: Goodin DS. Disease modifying therapies in multiple sclerosis. Neurology 22;58: Mc Donald WI, Fazekas F, Thompon AJ. Diagnosis of multiple sclerosis. Yh Nevrol Psichiatr Im 23;spec No2: Polman CH, Reingold SC, Edan G. et al. Diagnostic criteria for multiple sclerosis: 25 revisions to the Mc Donald criteria. Ann Neurol 25;58: Grgić S. Pain, depression and fatigue as significant symptoms in MS patients. Scholl of Medicine, Banja Luka, master s thesis, Khan F, Pallant J. Chronic pain in multiple sclerosis: prevalence,characteristics, and impact on quality of life in an Australian community cochort.j Pain 27;8: Svendsen KB, Jensen TS, Hansen HJ, Bach FW. Sensory function and quality of life in patients with multiple sclerosis and pain. Pain 25;114: Pollman W, Fenerberg W. Current managment of pain associated with multiple sclerosis. CNS Drugs 28;22: Grasso M, Clemenzi A, Tonini A, Pace L, Casillo P, Cuccaro A, Pompa A, Troisi E. Pain in multiple sclerosis: a clinical and instrumental approach. Mult Scler 28;14: Drulovic J, Pekmezovic T, Matejic B et al. Quality of life in patients with multiple sclerosis in Serbia. Acta Neurol Scand 27;115: Hadjimichael O, Kerns RD, Rizzo MA, Cutter G, Vollmer T. Persistent pain and uncomfortable sensations in persones with multiple sclerosis. Pain 27;127: Beard S, Hunn A, Wight J. Treatments for spasticity and pain in multiple sclerosis: a systematic review. Health Technol Assess 23;7: Goodin DS. Disease modifying therapies in multiple sclerosis. Neurology 22;58: Acknowledgements The authors wish to thank Jelena Drulović, MD, PhD and Tatjana Pekmezović, MD, PhD for their contributions in preparing this manuscript. Abbreviations: MS multiple sclerosis CNS central nervous system NRS Numerical Rating Scale VAS Visual Analog Scale SF-36 Shot Form(36) Health Survey EDSS Expanded Disability Status Scale 2 Curr Top Neurol Psychiatr Relat Discip. Vol XIX No. 3-4, September-December 211
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