Predictors of Pain Severity and its Impact on Quality of Life in Patients with Parkinson's Disease
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.325323
Source of Support: None, Conflict of Interest: None
Keywords: Motor disability, pain, Parkinson's disease, quality of life, severityKey Message: Pain is a common non-motor symptom reported by patients with Parkinson's disease (PD) in India. The presence of pain significantly correlates with increased motor disability and a poorer quality of life among Indian patients with PD.
Idiopathic Parkinson's disease (PD) is a common neurodegenerative disorder in older people. Non-motor symptoms of PD include autonomic dysfunction, sleep disorders, depression, anxiety, cognitive impairment, dementia, olfactory disturbances, and pain.,
Pain and other sensory manifestations are less widely appreciated while treating patients with PD. Occasionally, severe intractable pain can overshadow the motor symptoms of the disease as well. According to a survey, patients with PD perceive pain as one of the most troublesome symptoms in all stages of the disease. A recent review by the American Academy of Neurology did not mention pain in non-motor symptoms of PD. Moreover, the existing data regarding pain in PD is scarce from this part of the world. Hence, the study was conducted to evaluate pain and quality of life (QoL) in patients with PD.
The study was done between November 1, 2016 and August 31, 2018. One hundred PD patients who met inclusion criteria were recruited for this cross-sectional study. Written informed consent was obtained from all the subjects before inclusion in the study. Patients with PD were recruited irrespective of treatment duration, age, and sex. Exclusion criteria included risk factors for pain or other sensory symptoms such as diabetes, alcoholism, connective tissue disease, vitamin B12 deficiency, thyroid disease, malignancy, stroke, psychiatric illness, and exposure to neurotoxic drugs. Patients underwent diabetic screen, serum vitamin B12 levels, thyroid function tests, and HIV antibodies test. Further relevant investigations were done, if indicated. The study was approved by the institutional ethics committee.
Details of anti-Parkinsonian and other drugs in the form of doses were noted, and the duration of treatment was recorded. After collecting the demographic data, all the included patients were subjected to detailed clinical history and examination, including neurological assessment. Patients were assessed in an off-medication state. The stage and severity of PD was assessed according to Unified Parkinson's disease rating scales (UPDRS) III, V, and VI. Individual scores for each item were calculated and used to grade the disability of the patient for a particular aspect of the disease. We used UPDRS part Ill for motor evaluation, part V for Hoehn and Yahr staging, and part VI for ADL scale. King's Parkinson Disease Pain Scale (KPPS) was used for assessment of pain. It is a questionnaire with fourteen questions covering seven domains: (1) musculoskeletal pain, (2) chronic pain, (3) fluctuation-related pain, (4) nocturnal pain, (5) orofacial pain, (6) discoloration and edema/swelling, and (7) radicular pain. Each question is numbered for severity (range: 0–3) and frequency (range: 0–4) of pain.
QoL was assessed using the PDQ-8 questionnaire. It contains a total of 8 questions related to the QoL of the PD patient and each question has 5 choices depending upon the frequency of that symptom ranging from never to always. Scores are given from 0 to 4 for each item (good to bad) and the total score is calculated by adding all of them, which ranges from 0 to 32. PDQ-8 summary index (PDQ-8 SI) is calculated and it ranges from 0 (normal) to 100 (worse disability). In our cross-sectional study, the KPSS and the PDQ8 scales were applied at any time during the course of the disease and irrespective of the disease stage.
The number of PD patients with parkinsonian pain out of total PD patients was determined. Inter-correlations between pain and QoL were calculated. Inter-correlations between pain and motor severity of illness in PD patients were determined as well. Categorical variables were presented in number and percentage (%) and continuous variables were presented as mean ± SD and median. Unpaired t-test/Mann–Whitney Test was used to compare quantitative variables between the two groups. Pearson's correlation coefficient was used to assess the association of various quantitative parameters. P < 0.05 was considered statistically significant.
Among a total of 100 cases of PD, more than half of the subjects were in the 51–70-years age group. The mean age of male and female subjects was around 62 years with range of 38–85 years. Mean duration of disease in male and female subjects was 58.60 + 49.33 and 52.44 + 36.97 months, respectively. The male: female ratio was 3:1. The mean age of onset of disease of all subjects was 57.77 ± 12.05 years with range of 28–82 years. Twenty patients had disease duration of <2 years, while 34 cases had 2–4-years duration, and maximum 46 subjects were suffering from the disease for >4 years. Overall, the mean disease duration was 56.94 ± 46.22 months with a range of 3–240 months. There was no statistically significant difference for disease duration and age of onset between male and female groups (P > 0.05). Highest number of subjects (36) were at Hoehn and Yahr stage 2.5, while no patient was at stage zero. Maximum patients (71) were taking levodopa (LD)-containing regimens in various combinations with trihexyphenidyl (THP), pramipexol (PPX), rasagiline (RSGL), amantadine (AMTD), ropinirole (RPNR), entacapone (ECP), and others. Only 16 patients on treatment were taking regimens without LD, while 13 subjects were not receiving any treatment. Mean LEDD was 414.11 ± 318.99 mg with a maximum equivalent dose of 1577.5 mg. Mean UPDRS Ill, V, and VI scores were 15.01 ± 7.55, 2.40 ± 0.72, and 79.57 ± 18.70, respectively, with ranges of 2–40, 1–5, and 7–100, respectively [Table 1].
Out of 100 subjects, 70 exhibited one or more types of pain while 30 did not have any pain. The mean KPPS score of subjects was 5.23 ± 6.42 with a range of 0–27. The QoL indices in subjects with or without pain are depicted in [Table 2]. The individual types of pain, including musculoskeletal, chronic, fluctuation-related, nocturnal, orofacial, discoloration, and radicular pains, were present in 53, 13, 35, 27, 12, 11, and 17 subjects, respectively [Table 2].
Subjects revealing no pain had mean PDQ-8 and PDQ-8 SI scores of 3.30 ± 4.10 and 10.31 ± 12.82, respectively. The number of subjects showing 1, 2, 3, 4, 5, and 6 types of pain was 23, 20, 12, 8, 5, and 2, respectively, with respective mean PDQ-8 values of 6.35 ± 5.23, 7.65 ± 4.13, 8.58 ± 3.94, 14.25 ± 5.04, 13.80 ± 4.21, and 12.50 ± 6.36. Similarly, values were obtained for PDQ-8 SI scores. As the number of pain types increased, the PDQ-8 and PDQ-8 SI scores increased, meaning a poorer QoL in patients having more types of pain. None of the subjects showed all seven types of pain.
The linear regression analysis of KPPS with PDQ-8 and PDQ-8 SI showed positive correlations with a correlation coefficient (r) of 0.599, and this was statistically highly significant (P < 0.0001) [Table 3]. The difference among mean KPPS of different age groups, groups with different disease durations, different LEDD, different drug regimens, and gender groups were statistically insignificant (P > 0.05), meaning that pain scores were not affected by the variables such as age, gender, disease duration, LEDD, and use of anti-Parkinsonian drugs. The mean KPPS of subjects taking analgesics for pain and not taking analgesics were 8.90 ± 1.35 and 3.58 ± 0.62, respectively, with a significant P value of < 0.05, meaning that subjects with more pain (high KPPS) tend to take significantly more analgesics. The subjects with pain had younger age of onset and longer duration of the disease as compared to subjects without pain [Table 4].
The correlation of KPPS with UPDRS III and UPDRS V showed a positive linear relationship, whereas KPPS correlated negatively with UPDRS VI [Table 5].
The study determined the prevalence of pain symptoms, its impact on QoL, and its correlation with motor severity in a cohort of 100 PD patients from the Indian population. The baseline characteristics of age and disease duration did not differ significantly between male and female groups. Lin et al. reported average age of 66.24 ± 8.93 years (range: 35–85 years), which is comparable to our results. The present study had comparatively more number of male patients, which reflects the male preponderance among patients at our tertiary care center. The mean duration of the disease was 56.94 months. These results were comparable to the previous studies.
In the present study, 70% of subjects experienced one or more types of pain, with the mean KPPS score of 5.23 + 6.42. These findings are consistent with previously reported prevalence rates of 60%–83% in PD patients.,,,, Musculoskeletal pain has been reported as the most frequently occurring pain in PD, affecting 45%–70% of patients in previous studies.,,, Similar studies have reported variable prevalence of different types of pain.,,,
Subjects with pain had significantly poorer QoL as compared to subjects without pain. Similar findings were also reported in an earlier study by Rada et al. who noted significantly higher (P < 0.05) PDQ-39 scores in subjects with pain (32.81 ± 21.85) as compared to subjects without pain (20.28 ± 13.34). Prior studies investigating PD-related pain and depression have yielded contradictory results. Rana et al. found that pain in PD has a negative impact on ADL in a study of 121 PD patients. Roh et al. found a moderate correlation between the VAS score for pain and decreased QoL.
In the present study, mean PDQ-8 and PDQ- 8 SI scores differed significantly (P < 0.05) between subjects without pain and subjects with any of individual pain types, e.g. musculoskeletal, nocturnal, and radicular pain. Back pain is reported in 74% of PD patients, which may be due to many underlying etiologies.
The positive correlation between KPPS and PDQ-8 or PDQ-8 SI scores implies that as the severity of pain increases, the QoL decreases significantly in patients with PD. In a study on 291 PD patients, Skorvanek et al. found a significant correlation between pain, fatigue, and other sensations (non-motor MDS-UPDRS items) and PDQ-39 or its various subdomains on multiple linear regression analysis. Santos-García et al. probably carried out the first study to specifically correlate individual MDS-UPDRS non-motor items with QoL and its different domains. They found pain as an independent predictor of the worst QoL. Moreover, chronic pain is often associated with depression, which may further worsen the QoL among PD patients.
KPPS scores were higher in females than in males in our study. Social conditioning and sex hormones may be responsible for these gender-based differences. Studies suggest that women report pain more frequently than men. However, Zambito Marsala et al. (2011) and Mylius et al. (2009) did not report any gender-based differences in pain perception.
Subjects with pain had higher mean LEDD than those without pain in our study. This suggests that treatment for motor symptoms does have an impact on pain but it is not significant. Several anatomical, electrophysiological, and pharmacological arguments link PD-pain to the central dopaminergic deficit while central non-dopaminergic mechanisms cannot be excluded.,,,,,
On comparing the UPDRS scores between pain and without pain groups, the mean scores of UPDRS III, V, and VI were poorer in the pain group. These findings support the hypothesis that higher functional disability and advanced stages are associated with more pain in PD subjects. On correlating KPPS with UPDRS scores by linear regression the UPDRS Ill and UPDRS V had positive correlations with an r-value of 0.494 and 0.347, respectively. It means that KPPS scores increase with increase in UPDRS III and V, which are scales for motor severity and staging of the disease. The relationship of KPPS with UPDRS VI showed a negative linear correlation with r = 0.461 and this was also statistically significant (P < 0.05). As the ADLs worsen (decrease in UPDRS VI score) the KPPS scores increase, implying high pain intensity in advanced disease.
Our study had few limitations. These included the lack of an objective method of measuring pain perception in patients, as pain is a subjective sensation. The study was carried out at a tertiary-level movement disorder clinic and the study sample may not be truly representative of community distribution.
This study showed a high prevalence of pain among Indian PD patients. The presence of pain among PD subjects significantly affected the QoL, leading to poorer QoL as compared to PD subjects without pain. The findings of this study may have implications for designing further studies aimed at understanding underlying pain mechanisms in PD and identifying specific treatment strategies. Longitudinal studies are also required to understand how pain perception may change over the course of the disease.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1975 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all the patients included in the study.
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Conflicts of interest
There are no conflicts of interest.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]