Validation of the Ukrainian and Russian versions of the KPPS

. Background. The purpose of the study is to validate the Ukrainian and Russian versions of the King’s Parkinson’s disease Pain Scale (KPPS). Materials and methods. The study was conducted at the Odesa Regional Clinical Hospital in 2018–2020. We examined 160 patients with Parkinson’s disease verified by the Parkinson’s UK Brain Bank criteria (main group) and 100 people of the same age without signs of extrapyramidal pathology (controls). All patients were examined in accordance with the requirements of current clinical protocols. Additionally, all study participants answered the questions of the KPPS provided in the Ukrainian or Russian version. Mann-Whitney method with Benjamini-Hochberg correction was used for multiple comparisons. Results. Pain of varying severity was detected in 121 of 160 (75.6 %) patients with PD. There were no cases of pain in the control group. The most common was nocturnal (52.5 %) and musculoskeletal pain, both isolated (23.1 %) and in various combinations (up to 65.6 %). Pain associated with motor fluctuations occurred in 27 (5.1 %) cases. Central chronic pain was detected in 22 (13.8 %) patients, visceral chronic pain — in 11 (6.9 %). Orofacial pain was noted in 19 (11.9 %) cases. Pain associated with edema and signs of inflammation was found in 24 (15.0 %), radicular pain — in 17 (10.6 %) people. Cronbach’s alpha for all domains of the scale was higher than 0.7. Pain severity by the visual analogue scale correlated with the KPSS score (r = 0.53). Conclusions. The study data indicated the acceptable validity of the Ukrainian and Russian versions of the KPSS. The questionnaire can be recommended for widespread use in assessing the phenotype of pain and its severity in patients with Parkinson’s disease.


Introduction
Parkinsonism is a syndrome associated with lesions of the basal ganglia, which is manifested itself in hypokinesia, rigidity, rest tremor, and postural disorders [1][2][3].The main nosological form of parkinsonism is Parkinson's disease (PD), which accounts for about 70 % of cases [1] and is one of the leading in terms of prevalence among all neurodegenerative diseases.In a number of other nosological forms of parkinsonism, PD is characterized by a longer benign course and higher effectiveness of antiparkinsonian, primarily dopaminergic, drugs.
The main clinical manifestations of PD are tremor, rigidity, akinesia or bradykinesia, hypokinesia, and postural instability [1,4].In addition to motor disorders, non-motor symptoms are often reported in patients with PD, including autonomic symptoms such as hyperhidrosis, orthostatic hypotension, genital and urinary dysfunction, changes in thermoregulation, cardiovascular disorders, peripheral edema, sleep disorders, and neuropsychiatric disorders, including apathy, fatigue, anhedonia, depression, anxiety, panic attacks, cognitive impairment, etc. [4].Many patients experience a variety of sensory disturbances, including restless legs syndrome, numbness, paresthesia, visual disturbances, and pain [4,5].Among these sensory symptoms, pain is observed in approximately 30-50 % of patients with PD; however, some authors point to a higher frequency -up to 85 % [4][5][6].Pain can occur at any time during the disease, and in some cases, it is present before diagnosis [1,6,7].
The King's Parkinson's disease Pain Scale (KPPS), which is used in an interview format, has recently been introduced into practice.The questions of this scale are answered directly by the patient (if necessary, he/she is assisted by a nurse).This diagnostic tool was developed based on the advice of pain specialists, neurologists, nurses, Parkinson's Disease Non-Motor group and the International Parkinson and Movement Disorder Society guidelines.The scale distractors are based on the Chaudhuri-Shapiro pain classification used in the PANDA study (NCT01439100) [8].
The total score for each question is calculated by the formula: Х = a × b, where a -severity of pain (0 -no pain, 1 -mild pain (symptoms are present, but almost do not bother the patient), 2 -moderate pain, which slightly worries the patient, 3 -severe pain (significantly expressed and disturbing the patient)); b -frequency of pain (0 -never, 1 -rarely, i.e. less than 1 time per week, 2 -often (1 time per week), 3 -occurs several times a week, 4 -very often (daily or constantly)), giving a product in the range from 0 to 12.The sum for different domains gives a total of 0-168 points.
Nociceptive pain in PD is widespread (accounting for 40-90 % of reported cases of pain) [7,9].It is associated with PD and is divided into musculoskeletal and visceral.Musculoskeletal pain usually occurs due to abnormal posture, rigidity and akinesia, dystonia of the "exclusion" period.Exacerbation of dystonia early in the morning is typical, when dopaminergic stimulation is low and akinesia and rigidity are more pronounced.Often dystonia is manifested itself as focal, with plantar flexion and inversion of the foot.Another common type of nociceptive pain is visceral pain, which often results from constipation.Intestinal function in patients with PD depends on several factors, including autonomic insufficiency, which involves the intestinal nervous system.Dystonic contractions of the anal sphincter muscles can cause parcopresis and tenesmus [6,7,9].
Neuropathic pain associated with PD includes radicular and central pain [6,7,10].Radicular pain is more common in patients with PD than in the general population (14-35 vs. 10 %) [6,7].This high frequency probably reflects damage to the lumbar disc structure due to festination, kyphosis, and dystonia.Pain directly related to PD (central pain) is a relatively rare condition (4-10 % of cases) [1,6,7].In essence, this pain is detected ipsilaterally to the side of the body on which motor symptoms predominate.In contrast to the "classical" central pain, in PD this pain is not associated with a pronounced sensory deficit [7].Most researchers believe that the central type of pain in PD occurs directly due to dysfunction of the basal ganglia, which alters the sensory processing of nociceptive information.
Since the introduction of the scale in 2015, it has been validated in different language environments [8,11].The Mapi Research Trust (UK) is the copyright holder for the academic and practical use of the KPPS.As of September 1, 2020, the following validated national versions of the questionnaire were available: English (including for Australia), Bulgarian, Finnish, Swedish (Finland and Sweden), French (France and Canada), and Portuguese (Brazil), Slovak, Spanish (Spain and the United States), Greek, Hungarian, Italian, Japanese, Korean (South Korea), and Turkish.Thus, even 5 years after the introduction of the questionnaire in practice, this tool is not validated in most countries.Ukraine is not an exception.
When conducting valid research, the minimum number of respondents, as a rule, was 10 times higher than the number of the KPPS points (i.e.140 people) [8].To reduce systematic errors, this volume is often increased by 15-20 %.The number of patients in the control group may be less than in the experimental group, but not more than twice.
The purpose of the study is to validate the Ukrainian and Russian versions of the KPPS.

Materials and methods
The observational study was conducted at the Odesa Regional Clinical Hospital in 2018-2020.We examined 160 patients with PD verified by the UK Brain Bank criteria [1,12] (main group) and 100 people of the same age without signs of extrapyramidal pathology (controls).Permission for translation and validation was obtained from the Mapi Research Trust in advance.
All patients were examined in accordance with the requirements of current clinical protocols.Additio-nally, all study participants answered the questions of the KPPS provided in the Ukrainian or Russian versions (Fig. 1, 2).The language of the survey was chosen according to the respondents' preferences.In total, the Ukrainian-language version was chosen by 59 (36.9 %) patients of the main group, the remaining patients chose the Russian-language version.In the control group, half of the respondents answered the questions in Ukrainian and half -in Russian.
To compare the main and control groups, the Mann-Whitney method with Benjamini-Hochberg correction was used for multiple comparisons [13].

Results and discussion
When analyzing the prevalence of pain in patients with PD included in the regional register, it was found that 121 of 160 (75.6 %) had pain of varying severity (Table 1).There were no cases of pain in the control group.
The most common was nocturnal (52.5 %) and musculoskeletal pain, both isolated (23.1 %) and in various combinations (up to 65.6 %).In total, pain of various localizations associated with motor fluctuations occurred in 27 cases ( number of persons in the register (n = 527)).Central chronic pain was detected in 22 (13.8 %) cases, visceral chronic pain -in 11 (6.9 %).Orofacial pain was noted in 19 (11.9 %) people.Pain associated with edema and signs of inflammation was found in 24 (15.0 %) patients, radicular pain -in 17 (10.6 %).Most often, patients describe the pain as a kind of sensation without a clear localization or pain localized in the proximal extremities, usually on the side of more pronounced symptoms of parkinsonism.The pain was often deep, dull, aching, compres-sive, or itchy with localization in the neck, back, and extremities.In some cases, the pain had a bright autonomic feature, described by patients as "burning", "prickly" sensations that occurred in various areas of the body, including the mouth and genitals.The most common descriptors used by patients to evaluate pain were "dull" and "scorching."Less often, patients described tingling and numbness in the distal extremities.
Some authors report a direct relationship between the severity of pain and the stage of Parkinson's disease, starting with the on-Оригінальні дослідження / Original Researches set of the disease, when the pain occurs on the same side, where subsequently motor manifestations of PD appear.Interestingly, if pain occurs simultaneously with extrapyramidal motor symptoms or against the background of already permanent symptoms of PD, their localization also coincides [8].Regarding the severity of pain (Fig. 3), these data were very variable.In general, the intensity of pain correlated with the duration of the disease (r = 0.59) and the stage of PD (r = 0.64).
The total score on the KPPS subscales averaged 26.9 ± 2.0 points.The highest intensity was observed in pain associated with fluctuations -20.5 ± 6.1 points and in night pain -13.5 ± 2.0 points.
On the contrary, the intensity of orofacial pain was 8.4 ± 3.3 points, and of radicular pain -7.5 ± 2.7 points.With edema and signs of inflammation, the pain intensity corresponded to 9.9 ± 2.4 points.
When calculating the criteria, it was found that moderate and severe pain was detected significantly more often in the main group (Table 2).
As can be seen from the above data, statistically significant differences between the main and control groups were observed for all questions.
Factor analysis revealed three main latent factors that corresponded to 78% variance (CMO = 0.75; p < 0.001).The first factor is represented by musculoskeletal, visceral, nocturnal, and orofacial pain (conditionally called "chronic somatic pain").The second factor combined radicular pain and pain associated with edema (conditionally called "distal pain").The third factor was represented by pain associated with fluctuations and central pain (conditionally called "central pain").
When assessing the internal consistency, it was found that Cronbach's α (Table 2) for all domains of the questionnaire was higher than 0.7, which indicates a high degree of consistency.
The accuracy of the questionnaire scale was high, the probable error did not exceed 10 % of the actual estimate.
When comparing the results of pain intensity according to the visual analog scale and the actual score on the KPSS, a stable correlation of medium strength was found: r = 0.53.The homogeneity of the elements was equal to 0.21.
The limitations of the study related to high heterogeneity of the sample and selection bias were due to the difficulties of interpreting questionnaire items.2. The questionnaire can be recommended for widespread use in assessing the phenotype of pain and its intensity in PD patients.

Conclusions 1 .
The study data obtained indicate the acceptable validity of the Ukrainian and Russian versions of the KPSS.

Figure 1. KPPS for assessing severity of pain in PD, Ukrainian version
5.1 % of the total