CHRONIC PAIN AND MULTIMORBIDITY IN STROKE REHABILITATION

Adrian MELNIC1,2, Marina BULAI1, Oleg PASCAL1,2, Alisa TĂBÎRȚĂ1,

Svetlana PLEȘCA1,2, Victoria CHIHAI1.

1
Department of Medical Rehabilitation, Physical Medicine and Manual Therapy, „Nicolae
Testemitanu” State University of Medicine and Pharmacy, Chisinau, Republic of Moldova
2
Instutite of Neurology and Neurosurgery, „Diomid Gherman”, Chisinau, Republic of Moldova

Address for correspondence:

Adrian MELNIC
Department of Medical Rehabilitation, Physica lMedicine and Manual Therapy, “Nicolae
Testemitanu” State University of Medicine and Pharmacy, Chisinau, Republic of Moldova
Email: adrian.melnic@usmf.md
Adress: Republic of Moldova, Chisinau, street . Miron Costin 19/3. -25, MD2068, phone
+37361120460
ABSTRACT
Introduction: Chronic pain and multimorbidity are common among stroke survivors and can
negatively impact their functional outcomes and independence.
The aim of the study was to investigate the frequency of chronic pain and multimorbidity in
post-stroke patients, and their relationships with functional independence.
Methods: A database of 270 post-stroke patients consecutively enrolled in rehabilitation
programs were made. We recorded demographic data, the number of comorbidities, the presence
of pain, its intensity and localization, the number of pain regions, and the patient’s functional
independence. Nordic Musculoskeletal Questionnaire, VAS Scale, and Barthel Index were used
for this purpose. Statistical analysis was made with SPSS version 24, including descriptive
statistics and correlation.
Results: We revealed a mean number of 3,6 comorbidities, and 60 % of patients reported
presence of pain (42% of chronic and 18% acute pain). Musculoskeletal pain was the most
common type of pain (48.7%), followed by mixed (28.3%) and neuropathic pain (23.0%).
Positive correlation between age and the number of painful regions (r=0.366, p<0.001), as well
as the number of comorbidities (r=0.520, p<0.001), was registered. We found negative
correlations with functional independence (age: r= - 0.467, p<0.001; number of pain regions: r= -
0.227, p=0.016; number of comorbidities: r= - 0.552, p<0.001 and VAS r= -0.220, p=0.019). The
number of comorbidities was positively correlated with VAS (r=0.251, p=0.007).
Conclusion: Chronic musculoskeletal pain and multimorbidity had a negative impact on
outcomes and functional independence in post stroke rehabilitation.
Key words: stroke, rehabilitation, multimorbidity, musculoskeletal pain, chronic pain, disability

RÉSUMÉ
Douleur chronique et multimorbidité dans la réadaptation post-AVC
Introduction: La douleur chronique et la multimorbidité sont courantes chez les survivants d'un
AVC et peuvent avoir un impact négatif sur leurs résultats fonctionnels et leur indépendance.
Le but de l'étude était d'étudier la fréquence de la douleur chronique et de la multimorbidité
chez les patients post-AVC et leurs relations avec l'indépendance fonctionnelle.
Méthodes: Une base de données de 270 patients post-AVC inscrits consécutivement à un
programme de réadaptation a été constituée. Nous avons enregistré les données démographiques,
le nombre de comorbidités, la présence de la douleur, son intensité et sa localisation, le nombre
de régions douloureuses et l'indépendance fonctionnelle du patient. Le questionnaire musculo-
squelettique nordique, l'échelle VAS et l'indice de Barthel ont été utilisés à cette fin. L'analyse
statistique a été faite avec SPSS version 24, y compris les statistiques descriptives et la
corrélation.
Résultats: Nous avons mis en évidence un nombre moyen de 3,6 comorbidités, et 60 % des
patients ont signalé la présence de douleur (42 % de douleur chronique et 18 % aiguë). Les
douleurs musculo-squelettiques étaient le type de douleur le plus courant (48,7 %), suivies des
douleurs mixtes (28,3 %) et neuropathiques (23,0 %). Une corrélation positive entre l'âge et le
nombre de régions douloureuses (r=0,366, p<0,001), ainsi que le nombre de comorbidités
(r=0,520, p<0,001), a été enregistrée. Nous avons trouvé des corrélations négatives avec
l'indépendance fonctionnelle (âge : r= - 0,467, p<0,001 ; nombre de régions douloureuses : r= -
0,227, p=0,016 ; nombre de comorbidités : r= - 0,552, p<0,001 et EVA r= - 0,220, p=0,019). Le
nombre de comorbidités était positivement corrélé à l' intensité de la douleur (r=0,251, p=0,007).
Conclusion: La douleur musculo-squelettique chronique et la multimorbidité ont eu un impact
négatif sur les résultats et l'indépendance fonctionnelle dans la réadaptation post-AVC.
Mots-clés: accident vasculaire cérébral, réadaptation, multimorbidité, douleur musculo-
squelettique, douleur chronique, handicap

ABBREVIATIONS:
ADL: Activities of Daily Living
CP: Chronic Pain
CPSP: Central Post-Stroke Pain
CRPS: Complex Regional Pain Syndrome
IASP: International Association for the Study of Pain
MSK: Musculoskeletal
NMQ: Nordic Musculoskeletal Questionnaire
PSP: Post-Stroke Pain
SD: Standard Deviation
SPSS: Statistical Package for the Social Sciences
VAS: Visual Analog Scale
WHO – World Health Organization

INTRODUCTION
 Stroke is one of the most prevalent causes of disability worldwide. The growing
population of stroke survivors may experience a variety of comorbidities and complications,
such as physical disability, mood disorders, cognitive impairment, and post-stroke pain (PSP) 1.
Pain is common in both stroke survivors and in the general population. Pain after a stroke is a
frequent symptom that is poorly understood by many practitioners. It can be easily overlooked
due to its variable characteristics.
Chronic pain (CP) represents a common issue in stroke survivors, having a negative
impact on functional outcomes, independence in Activities of daily living ADL, and overall
function. In cooperation with the WHO, an IIASP Working Group has developed a classification
system. This is applicable in a wide range of contexts, including pain medicine and primary care.
According to the International Association for Study of Pain (IASP), CP is defined as pain that
persists or recurs for more than 3 months. In chronic pain syndromes, pain can be the sole or
leading complaint and requires special treatment and care 2.
The reported prevalence of chronic pain considerably varies, with figures ranging from
11 to 53% of stroke survivors, this variability may be related to differences in criteria and
methodologies used3. In addition, some studies report the development of novel pain after stroke
(or within the last 2 years) by 39.0% (35.1–43.0%) 3,4. The major specific conditions that affect
patients with stroke who develop pain include central post-stroke pain (CPSP), complex regional
pain syndrome (CRPS), and pain associated with spasticity or shoulder subluxation 3,5,6.
However, pain is not always directly correlated to stroke. Data from several studies
suggest that post-stroke pain is more common in patients with pain prior to the stroke, for
example. musculoskeletal pain 5,6. There is some overlap between these groups of chronic pain
conditions 6, 7.
Multimorbidity is commonly met in post-stroke rehabilitation patients. It is a rising
healthcare burden, internationally defined as: 'the co-existence of two or more chronic
conditions, where one is not necessarily more central than another' 8. Multimorbidity is
associated with a reduced health-related quality of life, increased mortality and poorer functional
status 9. As with patients with comorbidities, studies have shown that post-stroke treatment and
rehabilitation in patients with multimorbidity are linked with poorer outcomes 10. Comorbidity is
defined as the presence of one or more diseases in addition to the primary diagnosis, making the
difference between comorbidity and multimorbidity subtle, but significant for research and
guideline development purposes for such patients 11.
Schmidt et al. reported that the multimorbidity prevalence rate was 42.7% in adults
hospitalized after a first stroke, in a population-based cohort study (n=219,354). The
predominant co-morbidities encountered were atrial fibrillation or flutter (11.0%), cancer
(10.9%), diabetes mellitus (9.0%), congestive heart failure (8.1%), and chronic pulmonary
disease (8.1%) 12. Furthermore, the study shows that the association between multimorbidity and
stroke tends to increase with age. Additionally, in comparison with patients free of disability,
patients who had disability have demonstrated to be at a greater risk for developing an increased
number of diseases 13.
Like multimorbidity, chronic pain is frequently a burden for patients and clinicians.
Unfortunately, due to the complex nature of pain in stroke, it's presence amongst concurrent
morbidities (or possible cognitive and communication impairments) it may and poorly managed.
It is also important to mention that post-stroke pain tends to be refractory and may not fully
respond to medications or other forms of analgesic treatments. This contributes to the
challenging aspect of its management 14.
THE OBJECTIVE OF THE STUDY
The aim of this research was to investigate the relationship between multimorbidity and
chronic pain in post-stroke patients while taking into account pain characteristics, pain intensity,
localization, and functional independence.
MATERIALS AND METHODS
This study was a retrospective, descriptive analysis of a database of 270 post-stroke
patients enrolled consecutively in a rehabilitation program at the Clinical Hospital of the
Ministry of Health in Chisinau, Republic of Moldova, between January 2022 and January 2023.
Pain intensity was assessed through VAS (Visual Analog Scale), and Nordic Musculoskeletal
Questionnaire (NMQ) for the location and number of painful regions.
Chronic pain was considered any pain that lasted > 3 months. The presence of headache
was not analyzed in this sample focusing mainly on neuropathic or nociceptive pain.
Disability (functional independence status) was observed by the use of the Barthel Index.
The multimorbidity structure was taken from the medical records database including the
presence or absence of a list of the most common registered diagnosis. A multimorbidity number
of 1 was added to any additional diagnoses recorded in the database.
Statistical analysis was conducted using SPSS version 24, and data were reported as
frequency, percentage, mean, and standard deviation.
Descriptive statistics, correlations, and graphs such as boxplots, pie, and bar charts were
used to analyze the data.
A non-parametrical correlation analysis was conducted using Spearman's test (rho) to
determine the correlation between age, number of regions affected by pain, number of
comorbidities, VAS score, and Barthel Index.

RESULTS
Out of 270 patients, 213 (78.9%) had an ischemic stroke, and 57 (21.1%) had a -
hemorrhagic stroke. Of the total sample, 57.4% (n=155) were male, and 42.6% (n=115) were
female. The minimum and maximum values for age were 31 and 86 years, respectively, with a
mean of 63.31 years (SD= 9.5). The majority of patients, 61.9% (n=167), were enrolled in a
rehabilitation program in the chronic phase of stroke (> 6 months after onset).
The data shows that a significant number of patients in the study experienced chronic
pain (42.2%), while a smaller number experienced acute pain (18.1%). It is important to mention
that acute pain can develop into chronic pain, underscoring the need for effective pain
management strategies. The three categories of chronic pain considered are musculoskeletal
(MSK), neuropathic, and mixed. The results indicate that MSK pain was the most commonly
reported type, accounting for 48.7% of cases, followed by mixed pain which was reported by
28.3% of cases, and neuropathic pain, which was reported by 23.0% of cases. (Figure 1.)
The distribution of painful sites in the patients was recorded according to NMQ, as
follows: shoulder pain (n=97) was reported by 35.93% of patients, knee pain (n=54) by 20%,
lumbar pain (n=58) by 21.48%, pain in the hand/wrist (n=35) by 12.96%, cervical pain (n=39)
by 14.44%, ankle/foot pain (n=28) by 10.37%, hip pain (n=23) by 8.52%, elbow pain (n=18) by
6.67% and thoracic pain (n=12) by 4.44%.
 The results suggest that the distribution of painful sites in patients is varied, with some
types of pain being more common than others. It is important to note that these types of pain are
not mutually exclusive, and there can be an overlap between them. (Figure 2.)
Multimorbidity is also common in post-stroke rehabilitation. The mean number of
comorbidities was 3.62 (SD=1.47). The study found that the most common comorbidities among
stroke patients were cardio-vascular pathology. Hypertension was recorded in 83.7% (n=220) of
patients, followed by ischemic heart disease in 41% (n=111), heart failure in 59.3% (n=160), and
arrhythmias in 23.0% (n=62). Dyslipidemia and diabetes mellitus were also frequently
encountered multi-morbidities with rates of 31.5% (n=85) and 26.6% (n=72), respectively. Other
comorbidities, such as obesity, osteoarthritis, and osteoporosis, were less prevalent, with rates of
10.4% (n=28), 19.3% (n=52), and 4.1% (n=11), respectively. (Figure 3.)
It is also interesting to observe multimorbidity evolution in a post-stroke patient enrolled
in rehabilitation programs. Patients were stratified by the presence or absence of pain in the
sample. The patients with pain tend to have more multimorbidity, as the mean number of
comorbidities was 2.8 (SD=1.0), in patients that didn’t report any pain, in comparison with the
mean number of comorbidities in patients with pain, which was higher at 4.8 (SD=1.5) (Figure
4)
The mean Barthel Index was 72.6 points (SD=7.8) in patients without pain, and 66.5
(SD=15.9) in those with pain, suggesting that patients who reported pain tended to have lower
levels of functional independence compared to those who did not report pain.
Overall, the results suggest that patients who reported pain tended to have more
comorbidities, and had lower levels of functional independence compared to those who did not
report pain.
Additional analyses were performed in order to understand better the factors and
variables that showed association with the functional outcome, number of regions, outcomes and
the relation to age, painful sites, and the number of multimorbidity. (Table 1)
The correlation analysis shows that age has a significant positive correlation with both
the number of pain and the number of multimorbidity. The number of painful regions also has a
positive correlation with the number of comorbidities tends to increase as well. Additionally, as
the number of regions increases, so does the likelihood of having multimorbidity (more
additional diagnosis).
On the other hand, age has a significant negative correlation with the Barthel Index (r= -
0.491, p<0.001), which indicates that as age increases, the level of disability tends to increase as
well. The number of regions and the number of comorbidities both have negative correlations
with the Barthel Index (r= -409, p=0.016 and r= -0.564, p<0.001, respectively), indicating that as
the number of regions and comorbidities increase, the level of disability also tends to increase.
Also, the number of comorbidities has a positive correlation with the VAS (r=0.209,
p=0.007), indicating that as the number of comorbidities increases, the level of pain tends to
increase as well. The VAS also has a negative correlation with the Barthel Index (r= -0.244,
p=0.019), suggesting that as the level of pain increases, the level of disability tends to increase as
well.
These findings provide important information about the characteristics of individuals
with pain in a rehabilitation clinical setting. The moderate pain severity and functional status
scores indicate a need for effective pain management strategies that can improve patients' overall
well-being. Additionally, the relatively advanced age of the sample suggests that age-related
factors may play a role in the development and management of pain in this population.
DISCUSSION

There is limited research on the interaction between chronic pain and multimorbidity in
stroke populations, specifically on the direct results of the co-occurrence of these two.
Chronic pain and multimorbidity are both common phenomena that often co-occur in
stroke populations, yet the interaction between the two remains poorly understood. While the
study by Ferguson et al. (2020) sheds some light on the prevalence of pain in populations with
multimorbidity, there is limited research specifically focused on stroke populations 15.
As age increased, the number of painful regions and comorbidities tended to increase as
well, which is consistent with previous research on aging populations. Additionally, as the
number of painful regions increased, the probability of having more comorbidities also
increased. These findings highlight the importance of managing comorbidities in patients with
chronic pain, as they can significantly impact the overall health outcomes and quality of life.
The presence of comorbidities in stroke rehabilitation can have a significant impact on
rehabilitation outcomes, including the potential for the development of chronic pain. While the
benefits of rehabilitation after stroke is well-established, stroke patients with comorbid
conditions may experience slower progress during rehabilitation, leading to less benefits
obtained from rehabilitation. This burden of comorbid conditions may necessitate a longer
duration of rehabilitation, to achieve the functional gains required for discharge into the
community 14,16,17.
A retrospective cohort study encompassing a sizable cohort of 29,673 stroke patients
aged 66 years or older revealed that virtually all patients, i.e., 99.1%, manifested at least one co-
existing condition, while a considerable proportion, i.e., 58.2%, exhibited multiple co-
morbidities. Among the most commonly reported co-morbidities were hypertension, ischemic
heart disease, arthritis, and irritable bowel syndrome 18. While our results are consistent with
previous research, it is imperative to acknowledge that a limited list of co-morbidities are
employed in the ongoing research, based basically on those that are included in comorbidity
indexes, further investigations incorporating a broader spectrum of diagnostic categories may be
useful.
The nature of pain experienced by stroke patients is multifaceted. There is a need for
effective pain management strategies that take into account the different types and complexities
of pain and the presence of multiple conditions that affect overall patient health-related
outcomes.
At the same time, existing data supports our findings regarding the prevalence of chronic
pain in stroke survivors. According to Kong et al.'s (2004) study, chronic pain is a prevalent
issue among stroke survivors both during rehabilitation and after returning home. Chronic pain
may result from a variety of factors such as muscle weakness, joint stiffness, spasticity, and
sensory changes, and may manifest in different forms, including musculoskeletal pain,
neuropathic pain, and central pain syndrome. The study reported that 42% of stroke survivors
experienced chronic pain, with the majority experiencing musculoskeletal pain. Chronic pain has
a significant negative impact on the physical and emotional well-being of stroke survivors,
affecting their health-related quality of life. Therefore, the study highlights the importance of
addressing the issue of chronic pain in stroke rehabilitation programs19.
 As age increased, the number of painful regions and comorbidities tended to increase as
well, which is consistent with previous research on aging populations. Additionally, as the
number of painful regions increased, the likelihood of having more comorbidities also increased.
These findings highlight the importance of managing comorbidities in patients with chronic pain,
as they can significantly impact the overall health outcomes and quality of life.
Furthermore, the negative correlation between age and the Barthel Index, indicating that
as age increased, the level of disability tended to increase as well, is consistent with previous
research on stroke patients. The negative correlations between the number of painful regions and
comorbidities with the Barthel Index suggest that the presence of pain and comorbidities may
exacerbate disability in stroke patients.
Prospective data were collected over a two-year period, including patients with
acute/subacute ischemic stroke who received in-hospital rehabilitation treatment, and assessment
of functional status using the Rivermead Mobility Index, Barthel Index, and modified Rankin
Scale, and also comorbidity (with the modified Charlson Comorbidity Index). This found that
patients with more comorbidities had worse functional outcomes after stroke. Modified Charlson
Comorbidity Index, atrial fibrillation, and myocardial infarction are independent predictors of
rehabilitation success20.
Moreover, our research highlights an interesting, positive correlation between the number
of comorbidities and VAS, indicating that as the number of comorbidities increased, the intensity
of pain tended to increase as well. This is consistent with previous research on chronic pain
patients. Additionally, the negative correlation between the VAS and Barthel Index suggests that
the presence of pain may also exacerbate disability in stroke patients with chronic pain.
Finally, according to ICD-11, chronic pain is a separate condition that can coexist with
other conditions, including stroke. This recognition of chronic pain as a distinct entity suggests
that healthcare professionals should consider the idea of chronic pain as an additional
multimorbidity in stroke populations. Integrating chronic pain management into stroke
rehabilitation plans is crucial for improving patient outcomes and quality of life.

CONCLUSION
Chronic pain is a frequent issue among stroke patients, and it is possible that pain adds
additional comorbidity to this population (given that according to ICD-11, chronic pain is a
separate condition). It is important to note that among chronic pain, musculoskeletal pain is the
most common type reported by stroke patients. Therefore, managing chronic pain and
comorbidities, particularly musculoskeletal pain, in stroke patients is crucial for improving their
overall health outcomes and quality of life. Further research is needed to better understand the
relationship between chronic pain and comorbidities in stroke patients and to develop effective
interventions for managing these conditions.
 .
Author’s Contributions:

Conceptualization, A.M.. and O.P.; methodology, M.B..; software, A.M.; validation,A.T., S.P.
and V.C.; formal analysis, M.B.; investigation,V.C.; resources, data M.B.; curation, A.T. and
O.P.; writing—original draft preparation, S.P.; writing—review and editing, V.C., A.M,
A.T.,M.B.; visualization, A.M.. and M.B.; supervision, O.P.; project administration, V.C.. All the
authors have read and agreed with the final version of the article.

Compliance with Ethics Requirements:

“The authors declare no conflict of interest regarding this article”
”The authors declare that all the procedures and experiments of this study respect the ethical
standards in the Helsinki Declaration of 1975, as revised in 2008(5), as well as the national law.
Informed consent was obtained from all the patients included in the study”
“No funding for this study”
Acknowledgements:
None
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 A. B.

Figure 1. Types of pain in a stroke patient.

(The pie graphs (A. Pain by duration, B. Types within chronic pain ) (Pain overall is reported by
60 %, while chronic pain is present in 42 % of the stroke population. Within chronic pain, MSK
pain is reported as the most common.)
 Figure 2. Painful regions in post-stroke patients. (There is a dominant painful site related
to the shoulder. Among other frequent painful sites are the lumbar spine, knee, and cervical
spine, while the least common is the hip elbow, ankle/ foot, or thoracic spine)
 Figure 3. Multimorbidity structure in stroke.
(A visual representation of the detailed multimorbidity structure. The most commonly
observed comorbidities in the study were hypertension, heart failure, ischemic heart disease,
dyslipidemia, and diabetes mellitus, while other comorbidities such as osteoporosis, arthritic
disease, and obesity were less prevalent. CHD/ IHD – Coronary Heart Disease/ Ischemic Heart
Disease, OA – Osteoarthritis, Kidney Conditions, GC- Gastric Condition, Respiratory
Conditions)
 Figure 4. Presence of pain and a number of comorbidities.
(The mean number of comorbidities was 2.8 (SD=1.0), in patients that didn’t report any pain.
The mean number of comorbidities in patients with pain was higher at 4.5(SD=1.5)
 Table 1. Correlation test (Spearman’s rho) within age, number of regions, multimorbidity
number, VAS, and Barthel Index

1. 2. 3. 4. 5.
1. Age

2. Number of regions 0.301**

3. VAS 0.209* 0.141

4. Number of multi-morbidity 0.520** 0.206* 0.251**
5. Barthel Index -0.491** -0.173 -0.244** -0.564**

Note. The table shows the correlation coefficients between the demographic and clinical
variables. Significance levels are indicated by ** (p < 0.01) and * (p < 0.05).