Pain in Patients with Multiple Sclerosis a Population-Based Study

ORIGINAL CONTRIBUTION Pain in Patients With Multiple Sclerosis A Population-Based Study

Kristina Bacher Svendsen, MD; Troels Staehelin Jensen, MD; Kim Overvad, PhD; Hans Jacob Hansen, MD; Nils Koch-Henriksen, MD; Flemming W. Bach, MD

Background: Pain is an important symptom in pa- Results: Response rates for MS patients and reference sub- tients with multiple sclerosis (MS). The estimated pain jects were 81.3% and 63.3%, respectively. Pain in the month prevalence varies between 30% and 90%. To our knowl- preceding assessment occurred in 79.4% of MS patients and edge, previous studies do not include a whole popula- in 74.7% of reference subjects (prevalence proportion ration sample of patients with MS. tio, 1.06; 95% confidence interval, 0.99-1.13). Patients with MS had a higher pain intensity (“when pain is at its least” Objective: To assess pain prevalence and its clinical char- median visual analog scale score, 20.0 vs 11.0 mm [PϽ.01]; acteristics and impact on daily life in a population sample and “when pain is at its worst” median visual analog scale of MS patients and in a reference group. score, 68.0 vs 55.0 mm [PϽ.01]). Daily intake of analgesics occurred in 24.4% of MS patients and 9.0% of refer- Design: Postal survey. ence subjects (prevalence proportion ratio, 2.7; 95% confidence interval, 2.0-3.6). Patients with MS more often Setting: Aarhus County, Denmark. reported that pain interfered with daily life “most of the time” or “all the time.” Participants: The population of patients with definite MS in Aarhus County (n=771) and a sex- and age-stratified ref- Conclusions: The frequency of reported pain in MS patients erence group from the general population (n=769). was not higher than in the background population. How- ever, pain intensity, the need for analgesic treatment, and Main Outcome Measures: Pain prevalence, inten- the impact of pain on daily life were higher in MS patients. sity, and treatment requirement; and the impact of pain on daily life. Arch Neurol. 2003;60:1089-1094

ULTIPLE SCLEROSIS found that pain affected the ability of a pa- (MS) is a chronic dis- tient with MS to perform as a worker, part- ease with no curative ner, parent, and friend. treatment. Accord- The present study (a) assesses the ingly, symptomatic pain prevalence in the preceding month treatmentM is important. Pain has not pre- in a population sample of MS patients; (b) viously been considered an important el- assesses pain prevalence in a sex- and age- ement of MS, but in recent years, acute and stratified reference group from a back- chronic pain syndromes have been recog- ground population; and (c) compares pain nized as symptoms in patients with MS.1-11 prevalence, characteristics, treatment, and From the Danish Pain Research impact on daily life in the 2 groups. Center (Drs Svendsen, Jensen, The reported prevalence of pain in pa- and Bach) and the Department tients with MS differs considerably, with 1-3,5-14 of Neurology (Drs Jensen, figures ranging from 30% to 90%. Pre- METHODS Hansen, and Bach), Aarhus vious studies differ in design and type of University Hospital, Aarhus; pain registered. To our knowledge, no A postal survey concerning pain in the pre- the Department of study has been based on a representative ceding month was undertaken in the popula- Epidemiology and Social sample of the whole population of MS pa- tion of MS patients in Aarhus County, Den- Medicine, University of Aarhus, tients. mark, and in a sex- and age-stratified reference Aarhus (Dr Overvad); and the The presence of pain may influence group drawn from a general population. The Department of Neurology, population in Aarhus County includes 640000 quality of life and daily activities. In a pre- Aalborg Hospital, Aalborg, and 8 inhabitants. Invitations to participate, along the Danish Multiple Sclerosis vious study, one third of the MS patients with questionnaires, were mailed to potential Registry, Copenhagen indicated that pain was the worst symp- participants between January 18, and April 26, (Dr Koch-Henriksen), tom of MS. Archibald et al1 evaluated the 2001. Nonresponders received a reminder 1 Denmark. effect of pain on social performance, and month after the first mailing.

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©2003 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 dence intervals (CIs) were calculated. Bivariate analyses (Mantel- Danish Multiple Sclerosis Haenszel) were used to assess the impact of other pain treatment Registry Known in Not Known in on analgesic drug consumption. Differences in median visual the MS Clinic Patients With MS the MS Clinic analog scale scores were analyzed using the Mann-Whitney test. (n = 679) or Suspected MS (n = 180) in Aarhus County ␹2 Test statistics were used, comparing 2 or more frequencies (N = 860) (including pain treatment requirement and the impact of pain or physical health on daily life). Individuals with missing information from the questionnaire were excluded from the spe- Uncertain Dead Patients Diagnosis Diagnosis cific analysis. (n = 1) Letter Not Not or Patient to GP Registered Confirmed Not (n = 197) With a GP (n = 19) Informed? (n = 2) (n = 19) RESULTS At study start (December 12, 2000), 860 subjects in Diagnosis Confirmed Diagnosis GP Could Aarhus County who were 18 years or older were regis- and Patient Informed Confirmed Not Confirm (n = 641) and Diagnosis tered in the Danish Multiple Sclerosis Registry with defi- Patient (n = 36), 15 Informed Patient nite or probable MS (using the criteria of Poser et al ). (n = 130) Dead (n = 5), The inclusion and exclusion of patients is shown in Patient Unable to Figure 1. Questionnaires were mailed to 771 MS pa- Questionnaire Answer or tients and 769 reference subjects. After 1 written re- (n = 771) Not Aware About minder, 627 (81.3%) of the MS patients and 487 (63.3%) Diagnosis of the reference subjects had returned the question- (n = 23), Returning the GP Did Not naire. Nonresponders in the MS group were older than Questionnaire Know the responders; no difference was found in sex distribution. (n = 627) [81.3%]) Patient (n = 3) Nonresponders in the reference group did not deviate from (n = 67) responders regarding sex and age.

Figure 1. Inclusion and exclusion of patients in the study. The Multiple DEMOGRAPHIC CHARACTERISTICS Sclerosis Clinic was affiliated with the Department of Neurology, Aarhus University Hospital, Aarhus, Denmark. GP indicates general practitioner; MS, multiple sclerosis. No differences in sex distribution and age were found between MS patients and reference subjects (Table 1). The distribution in 10-year age groups was also equal in Patients with MS living in Aarhus County were identified the 2 groups when splitting the groups according to through the Danish Multiple Sclerosis Registry. Inclusion crite- sex. Patients with MS had a lower prevalence of re- ria were as follows: (a) living in Aarhus County, (b) definite MS ported muscle joint disorders than the reference sub- (criteria of Poser et al15), (c) 18 years or older, and (d) patient aware of the diagnosis. To ensure the correctness of the diagno- jects, while the prevalence of other diseases was similar sis and the patient’s awareness of the diagnosis, one of us (H.J.H.), (Table 1). The distribution of educational levels dif- from The MS Clinic, Aarhus, covering all inhabitants of the county, fered between the groups, with a lower educational reviewed the medical records for all patients known in the clinic. level in the MS group (Table 1). In case the patient was unknown in the clinic, the diagnosis was uncertain, or the patient’s knowledge about the diagnosis could MS DISEASE not be documented, the general practitioner was contacted. The general practitioner was asked whether she or he could confirm Of the 627 MS patients who responded to the question- the diagnosis and the patient’s awareness about the diagnosis and naire, 73 (11.6%) reported attacks in the preceding month approve the contact to the individual patient. (ie, an episode [Ն24 hours’ duration] with new neuro- Reference subjects were randomly selected from the same general population as MS patients. They were identified through logical symptoms or aggravation of existing neurological the Central Office of Civil Registration, in which all inhabit- symptoms not associated with fever). Of these 73 pa- ants in each area of Denmark are registered. We obtained in- tients, 46 (63.0%) reported pain during the attack. Of the formation about birth date, name, and address from the regis- 627 responders, 356 (56.8%) reported muscle spasms. Of ter. Inclusion criteria were as follows: (a) sex and age stratified these 356 patients, 47.7% reported painful muscle spasms. to patients with MS and (b) living in Aarhus County. The only exclusion criterion was a diagnosis of MS. PAIN A questionnaire was developed (data available from the authors). Questions about pain focused on pain experienced Pain Prevalence in the month preceding the assessment. Acute and chronic pain syndromes were included. If needed, participants were con- No difference in pain prevalence in the month preced- tacted by telephone for clarifying responses. The local ethical ing the assessment was found (498 [79.4%] of 627 re- committee and the Danish Data Protection Agency approved sponders in the MS group vs 364 [74.7%] of 487 re- the study, which was performed according to the Declaration sponders in the reference group reported pain) (PPR, 1.06; of Helsinki. Comparisons regarding demographic characteristics were 95% CI, 0.99-1.13). In the reference group, 74.0% (304/ conducted using the ␹2 test for categorical data and the non- 411) of subjects answering the first request had pain vs parametric Mann-Whitney test comparing median age. For pain 78.9% (60/76) of subjects answering the second request (including treatment and description) and abnormal sensa- (P=.36). The corresponding figures in the MS group were tions, prevalence proportion ratios (PPRs) with 95% confi- 78.7% (410/521) vs 83.0% (88/106) (P=.32).

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©2003 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 Table 1. Characteristics of Patients With MS Table 2. Pain Intensity and Reference Subjects* Patients Reference P Patients Reference Pain Variable With MS Subjects Value With MS Subjects P Verbal Rating Scale* Characteristic (n = 627) (n = 487) Value Mild 282 (60.9) 269 (77.7) Female-male ratio 1.93:1 1.77:1 .52 Moderate 162 (35.0) 70 (20.2) Ͻ.01 Age, median (range), y 52 (23-94) 52 (22-82) .62 Severe 19 (4.1) 7 (2.0) Disease duration, median 11.0 (1-60) NA NA VAS score, mm† (range), y “When pain is at its 20.0 (6.0-38.0) 11.0 (1.0-25.0) Ͻ.01 Other diseases least” Other neurological disease 34 (5.4) 16 (3.3) .08 “When pain is at its 68.0 (46.0-85.0) 55.0 (35.0-75.0) Ͻ.01 Cardiovascular disease 26 (4.1) 29 (6.0) .17 worst” Hypertension 62 (9.9) 46 (9.4) .79 Gastrointestinal disease 47 (7.5) 37 (7.6) .97 Abbreviations: MS, multiple sclerosis; VAS, visual analog sclae. Disease in the muscles 49 (7.8) 81 (16.6) Ͻ.001 *Data are given as number (valid percentage, ie, percentage based on the or joints number of subjects who answered the specific question) unless otherwise Cancer 15 (2.4) 16 (3.3) .38 indicated. Percentages are based on the total for each group and may not Diabetes mellitus 13 (2.1) 11 (2.3) .84 total 100 because of rounding. Differences between groups were analyzed ␹2 Metabolic disorder 20 (3.2) 15 (3.1) .91 using the test. There were 35 missing values for the patients with MS and 18 missing values for the reference subjects. Educational level, y† †Data are given as median (25th-75th percentile) unless otherwise indicated. Primary and secondary school‡ Differences between groups were analyzed using the Mann-Whitney test. Յ7 161 (25.9) 89 (18.5) 8-10 300 (48.3) 241 (50.2) Ͻ.01 Ͼ10 160 (25.8) 150 (31.2) the distribution of assessment in the 3 categories (mild, Training§ moderate, and severe) differed between the 2 groups 0 126 (21.3) 57 (12.4) ␹2 Ͻ 1-4 391 (66.2) 328 (71.3) Ͻ.01 ( =26, P .01), with a higher prevalence of MS pa- Ͼ4 74 (12.5) 75 (16.3) tients rating pain as moderate or severe than reference subjects. On the visual analog scale, MS patients re- Abbreviations: MS, multiple sclerosis; NA, data not applicable. ported a significantly higher pain intensity than refer- *Data are given as number (valid percentage, ie, percentage based on the ence subjects, “when pain is at its least” and “when pain number of subjects who answered the specific question) unless otherwise indicated. Categorical data were tested using the ␹2 test, and difference in is at its worst” (Table 2). age was analyzed using the Mann-Whitney test. †Percentages are based on the total for each category and may not total Pain Treatment 100 because of rounding. ‡There were 6 missing values for the patients with MS and 7 missing values for the reference subjects. More MS patients with pain than reference subjects with §There were 36 missing values for the patients with MS and 27 missing pain reported daily or constant treatment-requiring pain values for the reference subjects. (Table 3). Patients with MS more often reported an intake of analgesic drugs for 4 days or longer (44.4% vs Adjusting for other diseases, age, and sex, we found 24.4%) (PPR, 1.8; 95% CI, 1.5-2.2). Physiotherapeutic a higher prevalence of pain among MS patients than ref- pain treatment was more frequent in the patient group erence subjects (Mantel-Haenszel test; odds ratio, 1.45; 95% as well (44.4% vs 8.7%) (PPR, 5.1; 95% CI, 3.6-7.3). Pa- CI, 1.08-1.96). This difference was due to the difference tients undergoing physiotherapeutic treatment had the in reported muscle/joint diseases among the groups. same intake of analgesics as reference subjects undergo- Age was divided into 5 strata (Յ39, 40-49, 50-59, ing physiotherapeutic treatment, while MS patients not 60-69, and Ն70 years). In the MS group, we found a treated with physiotherapy had a higher consumption of higher prevalence of pain in the groups aged 40 to 49 analgesics than reference subjects not treated with phys- years (PPR, 1.24; 95% CI, 1.08-1.42) and 50 to 59 years iotherapy (41.3% vs 21.5%) (PPR, 1.9; 95% CI, 1.5-2.5). (PPR, 1.22; 95% CI, 1.06-1.40) (but not in the eldest age No differences were found for other types of pain man- groups) relative to the youngest age group. In the refer- agement, including acupuncture and chiropractic care. ence group, the pain prevalence in the eldest age group Of all MS patients, 24.4% (153/627) had a daily in- decreased relatively to the pain prevalence in the young- take of analgesic drugs compared with 9.0% (44/487) of est age group (PPR, 0.45; 95% CI, 0.32-0.64). Only in the reference subjects (PPR, 2.7; 95% CI, 2.0-3.6); of these the group that was 70 years and older, MS patients had patients and reference subjects, 37.3% and 29.5%, respec- a higher pain prevalence than reference subjects (PPR, tively, took more than 1 type of analgesic drug. Simple an- 1.35; 95% CI, 1.02-1.80). algesics (aspirin and acetaminophen), tricyclic antidepres- Disease duration (time since diagnosis) was divided sants, anticonvulsants, and opioids were more frequently into 5 strata (Յ5, 6-10, 11-15, 16-20, and Ն21 years). Pain used by MS patients than by reference subjects (Table 4). prevalence was not associated with disease duration. Pain Location Pain Intensity More MS patients with pain than reference subjects with In both groups, most subjects with pain assessed pain as pain reported pain in more than 1 location (81.3% vs mild on the Verbal Rating Scale (Table 2). However, 70.3%) (PPR, 1.16; 95% CI, 1.07-1.25). Pain in the eyes,

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Frequency of Patients Reference P Back Treatment-Requiring Pain* With MS Subjects Value Head “Never” 132 (27.7) 163 (46.7) Muscles “One or several times per month 117 (24.6) 95 (27.2) but not every week” Neck “One or several times per week 96 (20.2) 53 (15.2) Ͻ.001 Eyes but not every day” Abdomen “One or several times per day 52 (10.9) 21 (6.0) but not constantly” Chest Reference Subjects “Constant” 79 (16.6) 17 (4.9) Face Patients With MS

01020304050 60 70 Abbreviation: MS, multiple sclerosis. % of All Subjects *Data are given as number (vaild percentage, ie, percentage based on the number of subjects who answered the specific question) unless otherwise indicated. Percentages are based on the total for each group. For statistical Figure 2. Pain location for the patients with multiple sclerosis (MS) and the Ͻ analysis, the ␹2 test was used. There were 22 missing values for the patients reference subjects. The asterisk indicates a significant (P .001) difference with MS and 15 missing values for the reference subjects. between the 2 groups.

Table 4. Data for Medication Use Table 5. Pain Description*

Patients Reference Patients Reference With MS Subjects PPR With MS Subjects PPR Type of Medication (n = 612)* (n = 477)* (95% CI) Words Chosen† (n = 498)‡ (n = 364)‡ (95% CI) NSAIDs 38 (6.2) 21 (4.4) 1.41 (0.84-2.36) Throbbing 75 (15.1) 70 (19.2) 0.78 (0.49-1.24) Simple analgesics 66 (10.8) 28 (5.9) 1.84 (1.21-2.79) Shooting§ 181 (36.3) 103 (28.3) 1.28 (1.05-1.56) Anticonvulsants Stabbing 34 (6.8) 21 (5.8) 1.18 (0.70-1.98) In total 59 (9.6) 1 (0.2) 46.00 (15.20-139.40) Sharp 103 (20.7) 63 (17.3) 1.20 (0.90-1.60) For pain treatment 49 (8.0) 0 † Cramping§ 100 (20.0) 49 (13.5) 1.49 (1.10-2.03) Antidepressants Gnawing 81 (16.3) 50 (13.7) 1.18 (0.86-1.62) In total 68 (11.1) 18 (3.8) 2.94 (1.83-4.74) Hot/burning§ 114 (22.9) 37 (10.2) 2.25 (1.62-3.12) TCAs Aching§ 99 (19.9) 52 (14.3) 1.39 (1.03-1.88) In total 30 (4.9) 5 (1.0) 4.68 (2.01-10.90) Heavy§ 123 (24.7) 56 (15.4) 1.61 (1.22-2.13) For pain treatment 21 (3.4) 2 (0.4) 8.18 (2.46-27.19) Tender 88 (17.7) 52 (14.3) 1.24 (0.90-1.70) Opioids 42 (6.9) 9 (1.9) 3.64 (1.89-7.02) Splitting 7 (1.4) 3 (0.8) 1.71 (0.45-6.50) Spasmolytics 125 (20.4) 0 † Tiring/exhausting§ 242 (48.6) 105 (28.8) 1.68 (1.41-2.00) Interferon beta‡ 96 (15.3) 0 NA Sickening 23 (4.6) 20 (5.5) 0.84 (0.69-1.03) Fearful 28 (5.6) 11 (3.0) 1.86 (0.95-3.64) Abbreviations: CI, confidence interval; MS, multiple sclerosis; NA, data not Punishing/cruel 14 (2.8) 4 (1.1) 2.53 (0.89-7.20) applicable; NSAID, nonsteroidal anti-inflammatory drug; PPR, prevalence Other words 133 (26.7) 83 (22.8) 1.17 (0.92-1.48) proportion ratio; TCA, tricyclic antidepressant. No words 18 (3.6) 18 (4.9) 0.73 (0.39-1.38) *Data are given as number (valid percentage, ie, percentage based on the number of subjects who answered the specific question). There were 15 *Abbreviations are explained in the first footnote to Table 4. missing values for the patients with MS and 10 missing values for the †Words were chosen from Short Form–McGill Pain Questionnaire. Each reference subjects. subject could choose more than one word. †PϽ.001 (␹2 test) when comparing patients with MS with reference ‡Data are given as number (percentage) of all subjects with pain in each subjects. group. ‡Data are from medical records with no missing values. §Differences between groups are statistically significant (PϽ.05).

face, joints, and muscles and other types of pain in the arms/legs were more frequent in MS patients than in ref- tributions of answers in the strata differed between the erence subjects (Figure 2). 2 groups (␹2=57, PϽ.001).

Pain Description SENSORY SYMPTOMS

The words hot/burning, tiring/exhausting, heavy, Of the MS patients vs the reference subjects, 64.6% vs cramping, shooting, and aching were more frequently 19.3% reported abnormal sensations (PPR, 3.35; 95% used by the MS patients than the reference subjects CI, 2.86-3.92). Of these groups, 56.5% of the MS pa- (Table 5). tients and 77.7% of the reference subjects reported painful abnormal sensations. Dysesthesia (a painful or The Impact of Pain on Daily Life unpleasant sensation evoked by touch) was reported by 38.1% of the MS patients and 12.9% of the reference More MS patients than reference subjects reported that subjects (PPR, 2.95; 95% CI, 2.35-3.70). Abnormal sen- pain interfered with daily life “all the time” (19.3% vs sations occurred most frequently in the extremities in 7.4%) or “most of the time” (22.3% vs 12.0%). The dis- both groups.

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©2003 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 OTHER TREATMENT IN THE MS GROUP not represent a group of subjects with no or fewer symptoms related to a pertinent disease. However, we ac- Of the MS patients, 125 were treated with spasmolytic knowledge that the difference in response rates might have agents. Interferon beta was taken by 96 of the patients. biased the results toward more patients with pain in the (Information about interferon beta comes from medical reference group. records at The MS Clinic.) No difference in total pain was We were able to confirm the diagnosis of definite found between patients taking and not taking inter- MS (criteria of Poser et al15) for each patient included in feron beta. However, patients treated with interferon beta the study by reviewing medical records and/or contact- more frequently reported a headache (52.1% vs 38.0%) ing patients’ general practitioners. In the questionnaire, (PPR, 1.4; 95% CI, 1.1-1.8). the participants were asked about pain in the preceding month. The short period was chosen to avoid informa- THE IMPACT OF PHYSICAL HEALTH tion bias due to memory problems. We assume that most ON DAILY LIFE of the responders were able to recall significant pain during the past month. However, we cannot exclude that Of the MS patients, 45.0% found that physical health in- more MS patients than reference subjects had cognitive terfered with daily life all the time; the corresponding fig- problems with affected memory and problems recalling ure in the reference group was 7.2%. The difference in symptoms even within the past month. the distribution of answers in the strata between the 2 Only few studies concerning pain in MS patients in- groups was highly significant (␹2=339, PϽ.001). clude a reference group. In a study7 of sensory symptoms in 387 MS patients, a reference group, sex and age COMMENT matched with the patients but not randomly drawn from the general population, was included. The researchers re- To our knowledge, this is the first population-based study ported that no differences in prevalence of pain some time of pain in MS patients including a comparable reference in the past appeared between patients and control sub- group. No difference was found in the frequency of un- jects, but MS patients more often reported active pain. specific pain between the 2 groups, but treatment- In accordance with that information, we found no dif- requiring pain was more frequent among MS patients than ference between patients and reference subjects in pain in the sex- and age-stratified reference group. More than prevalence over time (1 month). We included chronic one quarter of the MS patients with pain reported daily and acute pain syndromes, and cannot provide an exact treatment-requiring pain, and 41.6% reported that pain estimate of the prevalence of active pain. In agreement interfered with daily life most or all of the time. with Rae-Grant et al,7 we found that MS patients more Possible selection and information biases need to be often reported pain in their extremities and face than ref- considered: (a) Did the included MS patients in fact rep- erence subjects. resent the population of MS patients in Aarhus County? The 1-month prevalence of pain was estimated to be (b) Was the reference group a representative sample from 53% in a previous study1 of 85 outpatients with MS. Of a background population? (c) Was the MS diagnosis cor- the patients with pain, 64% took analgesics during the past rect? (d) Was the information about pain from the ques- month. This is in agreement with our study, in which 20.9% tionnaire reliable? of the patients reported analgesic consumption for fewer Patients in Denmark with a diagnosis of suspected than 4 days and 44.4% reported analgesic consumption MS are reported to the Danish Multiple Sclerosis Regis- for 4 days or more in the past month (in total, 65.3%). try16; in addition, the MS registry receives files from the We did not find any association between disease du- National Registry of Patients (including all patient con- ration and pain. This is in agreement with 2 previous stud- tacts to hospitals in Denmark). Each case is evaluated, ies,1,7 whereas other studies2,6,8,18 found an association be- and if the criteria of Poser et al15 (definite or probable tween disease duration and the prevalence of pain. We MS) are not fulfilled, the patient is excluded from the MS defined disease duration as time since diagnosis, while registry. We cannot exclude that we missed a few pa- other studies might have chosen duration of symptoms tients with MS in Aarhus County. The diagnosis may have as the definition. We found a higher pain prevalence in been new and not registered in the MS registry yet. Fur- MS patients aged 40 to 59 years compared with the young- thermore, we excluded 23 patients because they were con- est age group (Յ39 years), while pain in the older age sidered unable to answer or the diagnosis was unknown groups was similar to that in the youngest age group. Other to the patients and/or their relatives. The reference group studies2,6 found a tendency toward higher pain preva- was randomly sampled from the general population lence in MS patients with increasing age. Because of the through the Central Office of Civil Registration (includ- limitations of a postal survey, information about disease ing all inhabitants in Denmark). The response rate was course and disability score was unavailable. higher in the MS group than in the reference group. How- PatientswithMSreportedalowerprevalenceofmuscle/ ever, we found no significant difference in pain preva- joint disease than reference subjects; otherwise, the groups lence between subjects answering the first request and were similar concerning other diseases. When other diseases subjects answering the second request, neither in the ref- wereincludedaspotentialconfoundingvariablesintheanaly- erence group nor in the MS group. In a Danish popula- sis, the pain prevalence in the MS group was statistically tion study,17 no difference in migraine prevalence be- higher than in the reference group. However, this differ- tween responders and nonresponders in the postal survey encedisappearedifmusculoskeletaldiseasewasnotincluded. was found, indicating that nonresponders probably do We find it likely that musculoskeletal disease may be un-

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©2003 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 derdiagnosed in MS patients because symptoms are wrongly sion of the manuscript for important intellectual content (Drs connected to MS. Therefore, the information about mus- Svendsen, Jensen, Overvad, Hansen, Koch-Henriksen, and culoskeletal disease from the questionnaire may not be re- Bach); statistical expertise (Drs Svendsen, Overvad, and liable. Based on this assumption, we suggest that the crude Koch-Henriksen); obtained funding (Drs Svendsen, Jensen, PPR of 1.06 (95% CI, 0.99-1.13) is the most correct expres- Hansen, and Bach); administrative, technical, and mate- sion of the relative prevalence of pain in MS patients com- rial support (Dr Bach); study supervision (Drs Jensen, Over- pared with reference subjects. vad, Hansen, Koch-Henriksen, and Bach). A lesion in the somatosensory pathways in the cen- This study was supported by grant 2001/71045 from tral nervous system may cause central pain, but pain can the Danish Multiple Sclerosis Society, Valby; grant J.664.28 also be due to musculoskeletal dysfunction as a conse- from the Warwara Larsen Foundation, Nykøbing Sjæl- quence of disability. About one third of the MS patients land, Denmark; grant 900035 from Manager Ejnar Jonas- have central pain.19,20 In the present study, 38.1% of the son and his wife’s memorial grant, administered by the Dan- MS patients reported touch-evoked dysesthesia and 36.5% ish Multiple Sclerosis Society; and a grant from the Karen reported painful abnormal sensations, which are char- Elise Jensens Foundation and grant 9700565 from the Dan- acteristic features of neuropathic pain.21 In addition, we ish Medical Research Council, Copenhagen. found that 22.9% of MS patients choose the pain descrip- We thank Jytte Frandsen and Vivi Brandt, RN, for their tor hot/burning, which has been claimed to be one of the technical assistance. most common qualities of central pain.20 However, 15.0% Corresponding author: Kristina Bacher Svendsen, MD, of the reference subjects also reported painful abnormal Danish Pain Research Center, Building 1A, Aarhus Univer- sensations and about 10.2% had hot/burning pain. In sity Hospital , Noerrebrogade 44, DK-8000 Aarhus C, Den- agreement with previous studies,5,7,14 we found that about mark (e-mail: [email protected]). 40.7% of the patients had back pain. The figure was not higher than in the reference group. Muscle/joint pain was more frequent in MS patients than in reference subjects. REFERENCES Of the MS patients, 39.6% had muscle pain and 41.9% 1. Archibald CJ, McGrath PJ, Ritvo PG, et al. Pain prevalence, severity and impact had pain localized to the joints. Earlier, tendon-skeletal in a clinic sample of multiple sclerosis patients. Pain. 1994;58:89-93. 10 pain was reported in 20% of MS patients. Pain located 2. Clifford DB, Trotter JL. Pain in multiple sclerosis. Arch Neurol. 1984;41:1270- at the muscle or joints may be compatible with muscu- 1272. 3. Indaco A, Iachetta C, Nappi C, Socci L, Carrieri PB. Chronic and acute pain syn- loskeletal pain, but can also represent a central pain phe- dromes in patients with multiple sclerosis. 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