Pain in patients with multiple sclerosis and its effect on selected aspects of the quality of life

Overview

Aim: To determine the mean intensity of currently experienced pain, its impact on behavioral and functional domains of life according to the The Medical Outcomes Study (MOS) Pain Effects Scale (PES) and currently experienced overall quality of life according to the Multiple Sclerosis Quality of Life 54 (MSQoL-54) in MS. Patients and methods: The quantitative observational study had 108 MS patients. The questionnaire included the Visual Analogue Scale (VAS) to assess the intensity of current pain, MOS PES to determine the impact of pain on selected functional and behavioral areas of the quality of life, and subjective perception of the overall quality of life using the item of the MSQoL-54. Descriptive statistics was used to evaluate averages and Spearman’s correlation coefficient to detect any relationship. Results: Patients reported a mean moderate pain intensity according to the VAS (M = 3.8). Pharmacotherapy was used by 66.7% of patients with the effect of occasional and frequent pain minimization; most commonly used drugs were nonsteroidal antiphlogistics (N = 55). Non-pharmacological methods were used by 36 patients with intermittent and frequent pain minimization; most used method was exercise. MOS PES showed a moderate effect of pain on functional and behavioral quality of life domains. According to the MSQoL-54, overall quality of life was rated as satisfactory (M = 5.8), and was rated lower with increasing pain intensity. Increasing pain intensity according to the MOS PES negatively affected mood, walking ability, sleep, activities of daily living, and recreational activities. Conclusion: Objectification of pain and identification of its impact on quality of life will help to improve individualized MS treatment.

Keywords:

Pain – Quality of life – Neurology – Multiple sclerosis – patient

This is an unauthorised machine translation into English made using the DeepL Translate Pro translator. The editors do not guarantee that the content of the article corresponds fully to the original language version.

 

Introduction

Multiple sclerosis is a serious chronic neurological disease, in the pathogenesis of which two basic components are applied -⁠ inflammatory and degenerative. Multiple risk factors are involved in the development of MS; it is a genetic predisposition combined with environmental factors. Genetic factors are responsible for 30% of the risk of developing the disease. Other factors include the composition of the gut microbiome, higher alcohol intake, childhood obesity and various infectious agents. There is a higher risk of developing MS in females and a higher progression in males [1].

Pain is one of the symptoms in the clinical picture of MS, the prevalence of which is reported in various studies in the range of 29-92% of patients, with an average of 61%. The etiology of its occurrence is quite broad and the accurate determination of pain is essential for the setting of therapy and management of the patient's overall condition. It is associated with a higher degree of disability as assessed by the Expanded Disability Status Scale (EDDS) [2]. Neuropathic and nociceptive pain are the most common, presenting more frequently and in higher frequency and percentage as MS progresses [3]. Neuropathic pain is related to the localization of the inflammatory process and damage to central pathways in the brain [2,4]. Within nociceptive pain, it is dominated by its musculoskeletal origin, which stems from altered movement stereotypes in motor dysfunction. The aforementioned type of pain also occurs with involvement of corticospinal pathways in optic neuritis. Pain in trigeminal neuralgia is a separate entity [2]. Psychogenic pain may also occur in MS [5]. Pain in patients with MS can potentially be related to the presence of other diseases such as headaches (migraine, tension-type cephalea), which are the most common [2]. In the context of the occurrence of pain in this group of patients, it is also necessary to mention the potential influence of MS treatment on its presence, such as pain with parenteral administration of glatiramer acetate, interferon. Pain during glatiramer acetate application may appear immediately after injection in the form of chest pain. It may also occur as a manifestation of a local reaction at the injection site after administration [6]. Pain may also be present with improper technique of administration of parenteral therapy preparations [7].

The type and etiology of pain is applied in the treatment. In neuropathic pain, tricyclic antidepressants, anticonvulsants are applied. In trigeminal neuralgia, the administration of anticonvulsants (carbamazepine, gabapentin, lamotrigine) is effective, including adjunctive treatment with the application of myorelaxants (baclofen) [5]. Opioids (tramadol) are applied as second-line treatment for neuropathic pain, as conventional analgesics and antiphlogistics are not very effective. In the treatment of nociceptive pain of musculoskeletal origin, physiotherapy is mainly applied [2].

The division of pain in terms of time is represented by the acute syndrome and chronic pain (present in 50-75% of patients) [4,5]. Despite the frequent occurrence of pain, the aforementioned symptom may be underdiagnosed in the context of other visible symptoms such as gait and balance disturbances, visual disturbances, and type of pain. It is also a factor negatively affecting daily functioning, sleep, mood, survival, perception of health, enjoyment of life, ability to work (employment), social contacts and quality of life [8-10].

Pain intensity can be objectively assessed in a given group of patients with a simple unidimensional self-assessment analogue scale, the Visual Analogue Scale (VAS) [2,3,10,11]. In the context of a holistic approach in the assessment of pain intensity in MS patients, unidimensional scales (such as the VAS) are sufficiently sensitive [12]. To assess the impact of pain on quality of life in MS patients, a self-assessment tool, The Medical Outcomes Study (MOS) Pain Effects Scale (PES), is available in clinical practice [13,14]. The MOS PES is part of the Multiple Sclerosis Quality of Life Inventory (MSQLI) tool. Another tool is the Multiple Sclerosis Quality of Life 54 (MSQoL-54). Multiple tools, generic or specific, can be used in the context of quality of life assessment. However, there is no consensus as to which quality of life assessment tool is most appropriate for a given patient group [15]. The verbalisation of the reduction in patients' quality of life is also conditioned by a deficit of self-sufficiency in activities of daily living, and more so in cases where they are dependent on the help of others, at risk of social isolation and limited ability to work. Other factors influencing quality of life include the type of MS and level of neurological disability, social support, educational attainment, age and employment [16].

Given the above background, we have set ourselves a number of objectives. To determine the average intensity of currently experienced pain in the patient population, the impact of pain on behavioral and functional domains of life according to the MOS PES, on the currently experienced overall quality of life according to the MSQoL-54, and to determine the existence of a significant relationship between the above variables.

 

Patíents and methodology

File

The cohort consisted of 163 adult MS patients. Selection into the cohort was deliberate, according to predefined inclusion criteria: patient age ≥ 18 years, diagnosed MS disease (G35 according to ICD-10) regardless of the duration of MS presence, verbalization of the presence of pain at the time of inclusion in the study, but must not result from an associated disease that is related to acute and chronic pain (vertebrogenic and rheumatic diseases, primary headache, oncologic diseases), and willingness to participate in the study by signing an informed consent form. Failure to meet at least one inclusion criterion was an indicator for exclusion. Precisely because of the presence of pain related to its occurrence as a symptom of an associated disease in MS patients, 55 respondents were excluded. Thus, based on the defined inclusion and exclusion criteria, we included 108 respondents in the final processing of the empirical data, of which 94 (87.0%) were women and 14 (13.0%) were men. The mean age of the cohort was 40.4 ± 9.8 years (min. 19, max. 70 years) with a mean duration of MS of 8.1 ± 7.4 years (min. 10 months, max. 32 years). Respondents with secondary education (55.6%) and employed full-time (45.4%) were the most represented. The presence of an associated disease was reported by 57 respondents, with endocrine (n = 19) and cardiovascular (n = 17) diseases being the most common.

 

Methodology

Study design: prospective cross-sectional observational study. A questionnaire method was used to collect empirical data. The first item of the questionnaire was information about the presence/experience of pain; in case of a positive answer, the patient proceeded to complete it. Unidimensional VAS was used to assess the currently felt pain intensity. The patient rated the intensity on a 0-10 scale, where 0 = no pain, 10 = maximal pain. Pain was rated in terms of intensity according to a numerical rating as follows: 1-3 = mild, 4-7 = moderate, 8-10 = severe [3]. The questionnaire further included the MOS PES instrument, which is part of the MSQLI. It contains six items and ascertains the impact of pain on selected functional and behavioral domains of quality of life in MS patients. For each item, the respondent answers on a 5-point Likert-type scale with a score range of 1-5 points (not at all = 1 point, a little = 2 points, moderately = 3 points, enough = 4 points, extremely = 5 points). The total score ranges from 6-30 points; the higher the score, the higher the impact on the selected quality of life domains [17]. Item 53 from the MSQoL-54 instrument was used to measure subjective perceptions of overall quality of life. Patients rate their quality of life on a 10-point analogue face scale, where 0 = worst possible quality, 10 = best possible quality [18]. Part of the questionnaire consisted of self-constructed items focusing on pain management (use of pharmacotherapy and frequency of use, which medications they specifically take, use of non-pharmacological methods). To ascertain the frequency of pharmacotherapy use, the patient chose from the following options: every day, < 3 times/week, ≥ 3 times/week, occasionally, never [3]. He indicated which option he most agreed with by circling. In the context of the use of pharmacotherapy and the use of non-pharmacological methods, we also focused on assessing the effect of the methods on pain relief. The patient circled the effect that he/she felt most closely described the effective method (pharmacotherapy, non-pharmacological methods) for relieving his/her pain: never, sometimes, often, always. Demographic items were also included in the questionnaire; gender, age, duration of MS, educational attainment, work status, and comorbidities were collected.

We created an electronic version of the questionnaire using Google Forms (Google, Mountain View, CA, USA) and distributed them via Facebook (Meta, Menlo Park, CA, USA) to two groups of MS patients. Seven MS patients were included in the pretest. Data collection took place in April 2023.

 

Analysis and evaluation of empirical data

The obtained empirical data were coded and transcribed into Microsoft Excel (Microsoft, Redmont, WA, USA) and evaluated in SPSS Statistics 26 statistical software (IBM, Armonk, NY, USA). Items focusing on pain management were evaluated using descriptive statistics; absolute (n) and relative (%) frequencies were calculated. Mean pain intensity (as measured by the VAS) and mean scores of perceived overall quality of life (as measured by item 53 of the MSQoL-54) were expressed via arithmetic mean (M), standard deviation (standard deviation; SD), minimum (min) and maximum (max) values as well as the impact of pain on functional and behavioral quality of life domains according to the MOS PES. Spearman's rank correlation coefficient (rS) was used to examine the relationship between currently perceived mean pain intensity and the functional and behavioral domains of life (MOS PES) and the relationship between currently perceived mean pain intensity (VAS) and overall perceived quality of life (item #53 from the MSQoL-54). The correlation coefficient is a number that takes on values ranging from -1 to +1. The correlation can be positive (a value close to +1) and negative (a value close to -1). If the value of rS is close to or equal to zero, then there is no relationship between the two variables being tested; it is a zero correlation [19]. The correlation coefficient rS is interpreted according to the specified threshold values, where 0.01 to 0.30/-0.1 to -0.30 is positive/negative weak correlation, 0.4 to 0.6/-0.4 to -0.6 is positive/negative moderate correlation, 0.7 to 0.9/-0.7 to -0.9 is positive/negative strong correlation, and 1/-1 is positive/negative very strong/perfect correlation [20]. All data were tested at the 5% significance level (p < 0.05).

 

Results

One of the objectives was to determine the intensity of the currently experienced pain, which was at the level of moderate (3.8 ± 2.3; min. 1, max. 9). In table 1, we present information regarding pain management. The results in Table 1 show that 66.7% of the patients are taking pharmacotherapy, which most often leads to intermittent or frequent pain minimization. Most patients (n = 55) take medications from the indication groups of non-steroidal antiphlogistic drugs. Non-pharmacological methods in pain management are used by 36 patients, which occasionally or frequently relieve the present pain. Most frequently, patients used exercise, physical methods (application of heat and cold), sleep and rest.

In Table 2, we report the mean values of the functional and behavioral quality of life domains of the patients according to the MOS PES. The results in Table 2 show that pain has a moderate impact on all functional and behavioral quality of life domains according to the MOS PES instrument. According to the overall mean score of 18.3 points, pain has a moderate impact on the quality of life domains assessed in the instrument.

Using item 53 of the MSQoL-54 instrument, the overall quality of life was rated as satisfactory by the patient population (5.8 ± 2.0, min. 0, max. 10).

We further investigated the existence of a relationship between currently experienced pain and the individual domains of quality of life according to the MOS PES and also the MOS PES as a whole, and between experienced pain and the perception of overall quality of life (item no. 53 of the MSQoL-54); the results are presented in Table 3. The results in Table 3 show that the relationships between pain and the five MOS PES quality of life attributes assessed came out as significant positive weak to moderate, indicating that increasing pain intensity has a negative impact on mood, ability to walk or move, sleep, and usual activities and recreational activities. The relationship between pain and enjoyment of life was not significant (p = 0.099).

Further, it is evident that there is a significant relationship between pain and perceptions of overall quality of life as measured by the MSQoL--54. The relationship is negative medium, which means that as the intensity of pain experienced increases, the perception of lower overall quality of life occurs.

 

Discussion

The study presents the results of the assessment of average currently experienced pain intensity and its impact on the behavioral and functional domains of quality of life according to the MOS PES and on the perception of overall quality of life according to the MSQoL -⁠ -54 during the study inclusion period. The results show that MS patients experience current pain, its intensity according to the unidimensional VAS scale is at the level of moderate. A similar value of mean current felt pain intensity was verbalized by patients in other studies [11,21]. In our study, according to the results, it is evident that patients use pharmacological and non-pharmacological methods in pain management. Pharmacotherapy is used by 66.7% of the patients. In comparison with other studies, the percentage of patients who use pharmacotherapy to minimize pain varies, e.g., 48% [22], 67.7% [23]. Based on these results, we can agree with the conclusions that MS patients more often require pharmacological treatment [22]. In our study, non-steroidal antiphlogistic drugs and anticonvulsants were the most frequently used pharmacological groups for pain relief. In comparison with other studies, respondents reported anticonvulsants and analgesics [3,10,23], anticonvulsants and tricyclic antidepressants most frequently [22]. In the above context, it should be noted that the application of specific indication groups of pharmacotherapy is related to the pathophysiological mechanisms of pain in a given disease (e.g., trigeminal neuralgia, headache, Lhermitte's symptom) [24]. In pain management, cannabinoids, myorelaxants, anticonvulsants, antidepressants, and botulinum toxin are recommended to minimize pain in a given group of patients [25]. In our study, patients also used non-pharmacological methods to relieve pain, the most frequently reported exercise in the form of aerobic exercise (strength training), stretching and yoga. Aerobic exercise is recommended in MS patients and should be part of any multidisciplinary pain management plan, but it must be tolerated and safe by the patient. Yoga is a form of physical activity recommended in this group of patients to minimize pain [25].

Another aim was to determine the impact of pain on selected aspects of quality of life. The results of our study confirmed its significant impact on the behavioural and functional domains of quality of life according to the MOS PES instrument. Pain is related to the performance of daily activities, employment and quality of life in MS patients [22] and mood [23]. It is the limited ability to move, walk and impaired coordination of movements that is assessed in the functional domain of quality of life that also negatively affects the behavioural domain of quality of life. This is the impact on mood (depressive tuning) and emotions (negative) [12,23]. Our study, in comparison with other studies, confirms that pain is both a symptom and a problem in a given group of patients with spillover into multiple domains of life with a negative impact on quality of life, as evidenced by several studies [3,10]. At the same time, the study confirms the presence of pain in a given group of patients, thus pointing to the importance of its objectification, which is also possible through a simple screening tool.

The research study also has its limitations: the aim of the paper was not to objectify the types of pain in a given group of patients, nor to detect differences in pain with respect to demographic variables such as gender, age, disease duration, educational attainment and work status. Another limitation is that the type of SM and the degree of neurological disability according to the EDSS were not assessed in relation to the method of data collection.

 

Conclusion

According to the results of our study, patients with SM experience pain at a level of moderate intensity, in the management of which they use a combination of pharmacotherapy and non-pharmacological methods. The present pain has a moderate impact on all domains of quality of life according to the MOS PES instrument. Overall quality of life was rated as satisfactory, but with increasing intensity of pain experienced, there is a perception of lower overall quality of life.

Objectification of the current pain experienced by MS patients represents an initial step in effective pain management. Identifying the methods preferred by the patients themselves may point to methods of pain relief that are appropriate for them. Similarly, identifying its impact on selected areas of quality of life will help to streamline the provision of individualised treatment for the disease and thus improve the quality of life of a given group of patients.

 

Acknowledgements

The authors thank all MS patients willing to complete the questionnaire.

 

Ethical aspects

The work was carried out in compliance with the Helsinki Declaration of 1975 and its revisions in 2004 and 2008. The work was approved by the Ethics Mission of the Jessenius Medical Faculty of Comenius University in Martin (30 March 2023, approval no.: EK 25/2023).

 

Conflict of interest

The authors declare that they have no conflict of interest in relation to the subject of the study. Patients signed an Informed Consent for inclusion in the study.

 

Table 1. Pain management in the cohort (n = 108).

Taking pharmacotherapy to minimize pain	n (%)
Yes	72 (66,7)
Frequency of use of pharmacotherapy
every day	19 (17,6)
˃ 3 times/week	15 (13,9)
˂ 3 times/week	18 (16,7)
Occasionally	47 (43,5)
never	9 (8,3)
Does the medication relieve the pain present?
occasionally	39 (54,2)
often	28 (38,9)
Indication group of pharmacotherapy used
non-steroidal anti-inflammatory drugs	55 (76,4)
anticonvulsant	10 (13,9)
analgesics	7 (9,7)
myorelaxants	5 (7,0)
Use of non-pharmacological methods to minimize pain
Yes	36 (33,3)
Do the methods used alleviate the pain present?
occasionally	23 (63,9)
often	12 (33,3)
Methods they apply in relieving pain
exercise (strength training, stretching, yoga)	10 (27,8)
heat/cool (infrared lamp, cooling and menthol creams, massage ointments, dry ice, warming compresses and wraps)	6 (16,7)
sleep and rest	3 (8,3)

% -⁠ relative abundance; n -⁠ absolute abundance

Table 2. Functional and behavioral quality of life domains according to the MOS PES in the cohort (n = 108).

Functional and behavioural quality of life assessment	M	SD	Min.	Max.
mood	3,1	0,9	1	5
ability to walk or move	2,9	1,1	1	5
Sleep	3,0	1,2	1	5
current activities	3,1	1,0	1	5
recreational activities	3,1	1,1	1	5
joy of life	3,1	1,2	1	5
overall average MOS PES score	18,3	4,6	6	30

not at all = 1 point; a little = 2 points; moderately = 3 points; enough = 4 points; extremely = 5 points

M -⁠ arithmetic mean; Max -⁠ maximum value; Min -⁠ minimum value; MOS PES -⁠ The Medical Outcomes Study Pain Effects Scale; n -⁠ number; SD -⁠ standard deviation

 

Table 3. Relationship between VAS and MOS PES and VAS and perceptions of overall quality of life according to the MSQoL-54 in the cohort (n = 108).

mean intensity of currently experienced pain and functional, behavioural domain (MOS PES)	rs	p
pain and mood	0,307	0,001
pain and the ability to walk or move	0,200	0,038
pain and sleep	0,296	0,002
pain and normal activities	0,265	0,006
pain and recreational activities	0,283	0,003
pain and joy of life	0,159	0,099
pain and average MOS PES score as a whole	0,340	< 0,001
pain and mean score of perceived overall quality of life (MSQoL-54)	-0,327	0,001

MOS PES -⁠ The Medical Outcomes Study Pain Effects Scale; MSQoL-54 -⁠ Multiple Sclerosis Quality of Life; n -⁠ number; r_s -⁠ Spearman's correlation coefficient; VAS -⁠ Visual Analogue Scale