International Journal of Environmental Research and Public Health Article Central Sensitization and Chronic Pain Personality Profile: Is There New Evidence? A Case-Control Study Marina Lopez-Ruiz 1,† , Andrea Doreste Soler 2 , Jesus Pujol 2,3 , Josep-Maria Losilla 4 , Fabiola Ojeda 5 , Laura Blanco-Hinojo 2,3 , Gerard Martínez-Vilavella 2 , Teresa Gutiérrez-Rosado 6 , Jordi Monfort 3 and Joan Deus 2,6, *,† 1 HM Hospital Sant Jordi, 08030 Barcelona, Spain 2 MRI Research Unit, Department of Radiology, Hospital del Mar, 08003 Barcelona, Spain 3 Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM G21, 08003 Barcelona, Spain 4 Department of Methodology, Faculty of Psychology, Autonomous University of Barcelona (UAB), 08193 Barcelona, Spain 5 Rheumatology Service, Hospital del Mar, 08003 Barcelona, Spain 6 Department of Clinical and Health Psychology, Universitat Autònoma de Barcelona, Bellaterra, 08193 Barcelona, Spain * Correspondence: joan.deus@uab.cat; Tel.: +34-93-581-44-53 † These authors contributed equally to this work. Abstract: Background: Personality traits are relevant for pain perception in persistent pain disorders, although they have not been studied in depth in sensitized and nonsensitized patients with knee osteoarthritis (OA). Objective: To explain and compare the personality profile of patients with OA, with and without central sensitization (CS), and fibromyalgia (FM). Setting: Participants were selected at the Rheumatology Department in two major hospitals in Spain. Participants: Case-control study where the sample consists of 15 patients with OA and CS (OA-CS), 31 OA without CS (OA-noCS), Citation: Lopez-Ruiz, M.; Doreste 47 FM, and 22 controls. We used a rigorous and systematic process that ensured the sample strictly Soler, A.; Pujol, J.; Losilla, J.-M.; fulfilled all the inclusion/exclusion criteria, so the sample is very well delimited. Primary outcome Ojeda, F.; Blanco-Hinojo, L.; measures: Personality was assessed by the Temperament and Character Inventory of Cloninger. Martínez-Vilavella, G.; Results: The percentile in harm-avoidance dimension for the FM group is higher compared to OA Gutiérrez-Rosado, T.; Monfort, J.; groups and controls. The most frequent temperamental profiles in patients are cautious, methodical, Deus, J. Central Sensitization and and explosive. Patients with FM are more likely to report larger scores in harm-avoidance, with an Chronic Pain Personality Profile: Is increase in logistic regression adjusted odds ratio (ORadj ) between 4.2% and 70.2%. Conclusions: There New Evidence? A Harm-avoidance seems to be the most important dimension in personality patients with chronic Case-Control Study. Int. J. Environ. pain, as previously found. We found no differences between OA groups and between sensitized Res. Public Health 2023, 20, 2935. groups, but there are differences between FM and OA-noCS, so harm-avoidance might be the key to https://doi.org/10.3390/ ijerph20042935 describe personality in patients with CS rather than the presence of prolonged pain, as found in the literature before. Academic Editor: Paul B. Tchounwou Received: 19 December 2022 Keywords: osteoarthritis; fibromyalgia; central sensitization; personality Revised: 1 February 2023 Accepted: 7 February 2023 Published: 8 February 2023 1. Introduction It is known that personality, a person’s predispositions and patterns of thinking, feeling, and acting [1], plays a very important role in humans. Its main characteristics are Copyright: © 2023 by the authors. that it predicts important outcomes and is stable across the lifespan. Thus, personality Licensee MDPI, Basel, Switzerland. traits manifest in a wide selection of behaviors both across contexts and over time [2]. It is This article is an open access article easy to understand that personality will affect health, including pain. We already know distributed under the terms and conditions of the Creative Commons that personality affects cancer or heart disease risk [1], smoking [3], patients’ satisfaction Attribution (CC BY) license (https:// and clinical outcome after total knee arthroplasty [4], or quality of life [5], among others. creativecommons.org/licenses/by/ We would like to focus on two pathologies where chronic pain (CP) is the main feature. 4.0/). The first is osteoarthritis (OA), which is already one of the ten most disabling diseases in Int. J. Environ. Res. Public Health 2023, 20, 2935. https://doi.org/10.3390/ijerph20042935 https://www.mdpi.com/journal/ijerph Int. J. Environ. Res. Public Health 2023, 20, 2935 2 of 13 developed countries. The worldwide estimates are that 9.6% of men and 18% of women aged over 60 years have symptomatic osteoarthritis [6]. The second is fibromyalgia (FM), which is one of the most common CP conditions and probably the most famous. FM affects an estimated 3–6% of the world’s population, mostly women, rising in incidence with age [7]. Even if it is obvious that OA and FM are quite different, beyond chronic pain, there is a feature where both pathologies connect the sensitization. In particular, we focus on central sensitization (CS), which is defined as pain hypersensitivity, tactile allodynia, pressure hyperalgesia, aftersensations, and enhanced temporal summation [8]. In FM, the sensitization is one of the main characteristics [9,10] characterized by the dysfunction of neurocircuits, among them the perception, transmission, and processing of afferent nociceptive stimuli [11]; whereas in OA, sensitization tends to occur later in the disease and it is present in some patients but not in others [12,13] and may explain the difference in severity and resistance to analgesic treatment [14]. Psychological and personality factors should be considered an important contributor in the processing of CP, as we know that they play a role in modulating therapeutic responses and pain perception [15,16]. Personality has been a focus of research to understand its influences both on other psychological factors and on medical diseases. One theory of personality, which has neurobiological correlations, is the Biological Personality Theory of Robert Cloninger. This theory postulates that there are four dimensions of temperament (novelty-seeking: NS, harm-avoidance: HA, reward dependence: RD, and persistence: P) and three dimensions of character (self-directedness: SD, cooperativeness: C, and self- transcendence: ST). Temperament is stable and heritable; character can flow and be learned. In fact, FM is one of those pathologies where personality has been studied. Following the theory of Cloninger, it seems that there is a personality profile for FM: high scores of HA and low scores of SD [17–19]. Thus, FM patients are predisposed to acquire conditioned responses of avoidance to adverse stimuli, or potential danger, and are also inflexible or unable to adapt to the situation, compared to control subjects. Low scores of NS [17,20] have also been found in many CP diseases, not only in the personality profile of FM. To clarify the amount of outcomes in this issue and look for a common denominator in FM personality traits, Conrad et al. [21] made a review and concluded that high HA combined with low SD contributes to chronicity of pain, and that it is associated with avoidant coping strategies and catastrophic interpretation of signals of danger and punishment. Little is known in the field of personality in OA, although it is the most prevalent musculoskeletal disease; presumably, plenty of OA patients suffer CP, and there are studies that show that the patient’s personality predicts recovery after total knee arthroplasty [22]. Çidem, Rezvani, and Karacan [23] studied personality in patients with knee OA, defined as affective temperament (depressive, hyperthymic, cyclothymic, irritable, and anxious), which describes the attitudes and behavior of individuals based on the constitutional, genetic, and biological factors. In knee OA patients, depressive temperament (hypercriti- cal or complaining, passive or indecisive, self-critical, pessimistic, incapable of fun, and becoming worried) was the most common dominant affective temperament. However, they found no correlation between pain alleviation by physical therapy and dominant affective temperament, so no relationship between pain and personality. Many studies agree that there is a CP personality [21,24–26]; however, to the best of our knowledge there are no studies where CS personality traits are investigated, even when there is a growing tendency to somehow accept the existence of a personality of chronic pain patients [27]. Therefore, the aim of this study is to determine the temperament and character profiles of patients with knee OA, with and without CS, and compare them to the temperament and character profiles of FM patients as a prototypical central sensitization syndrome, and also to study the temperamental profile of patients with OA and FM to know how often it could become a personality disorder. Cloninger [28,29] explains personality disorders defined by temperamental profiles when the SD and CO character dimensions score low or below the 33–35th percentile, suggesting a lack of self-control and problems adjusting with the defined temperamental profile. Several meta-analyses have studied the effect size of the Int. J. Environ. Res. Public Health 2023, 20, 2935 3 of 13 correlation coefficients between each of the temperament/character traits and personality disorder symptoms [30]. Based on the above information, it has been hypothesized that the personality profile in different chronic pain pathologies is mediated by the presence of central sensitization syndrome. 2. Materials and Methods 2.1. Participants The initial sample was composed of 90 patients with knee OA diagnosis and 150 with FM diagnosis at the Rheumatology Department in two major hospitals in Spain (Hospital CIMA Sanitas and Hospital del Mar), selected by a senior rheumatologist and a senior clinical psychologist during an 18 month period. There was a control group with 35 participants. Patients with OA were divided into 2 groups: (1) presence of clinical central sensiti- zation, defined by the presence of both spreading sensitization and temporal summation to repeated pressure pain stimulation [8,12,31–33] (OA-CS group); and (2) absence of CS (OA-noCS group). The principal inclusion criteria for the OA patients were: 1. Radiological and clinical diagnosis of knee OA based on the American College of Rheumatology (ACR) criteria, affecting at least one knee with a minimum of 3 months of symptom duration prior to screening. 2. Male or female (nonchildbearing potential) at least 45 years old. 3. A minimum of 4 out of 10 on the numerical rating scale (item 5 of Brief Pain Inventory) at screening and/or a requirement for the use of an analgesic for the knee pain. The specific inclusion criteria for the OA-CS group were: 1. Clinical evidence of pain or altered sensations spread beyond the knee joint by manual palpation in the baseline rheumatologist assessment. 2. At least 3 tender points in the extended version of the Arendt–Nielsen peripatellar map (excluding points 3, 7, and 8, which are part of the joint itself). A tender point is defined as a point showing a pressure pain threshold below 4 kg/cm2 [34]. 3. A pain score of 4 points or more in an 11-point verbal scale during a 2 s, 4 kg/cm2 pressure stimulation on the anterior surface of the tibial bone. 4. Presence of temporal summation (increase of more than 1 point in an 11-point verbal scale after 10 repeated pressure stimulation at 1 s interstimulus intervals) on the most sensitive site of the peripatellar region [11]. The principal inclusion criteria for FM patients were: 1. Diagnosis of FM following the ACR criteria [34]. 2. History of widespread nonarticular pain with insidious onset primary over 3 months. 3. One year minimum of disease evolution. 4. Absence of comorbid chronic fatigue syndrome. Inclusion criteria for control group were: 1. No history of rheumatic disorder, no history of functional pain or physical widespread pain. 2. No history of Axis I or II psychiatric illness and no history of neurological disease. Additionally, control participants underwent a brief semistructured clinical psy- chopathological interview according to DSM-5 diagnostic criteria carried out by a senior member of the research team (JD) to rule out any personality disorder. A convenience sampling was carried out where the researcher selects the patients who are easily accessible in a waiting room, through a satisfaction survey of the health system. In all groups, patients with a history of psychotic disorder or substance abuse, pa- tients with a history or diagnosis of personality disorders, and patients with a history of neuropathic pain were not included. A flow chart of the sample selected is shown in Figure 1. ble in a waiting room, through a satisfaction survey of the health system. In all groups, patients with a history of psychotic disorder or substance abuse, pa- tients with a history or diagnosis of personality disorders, and patients with a history of neuropathic pain were not included. A flow chart of the sample selected is shown in Fig- ure 1. Int. J. Environ. Res. Public Health 2023, 20, 2935 4 of 13 OA subjects (n=90) FM subjects (n=150) 1st day. Do they meet radiological and clinical 1st day. Do they meet FM criteria and signed criteria signed informed consent? informed consent? No (n=26) Yes (n=64) No (n=58) Yes (n=98) Do they meet Central Sensitization criteria? CS (n=19) no-CS (n=45) Do they finish psychological Do they finish psychological Do they finish psychological assessment? assessment? assessment? No (n=4) No (n=14) No (n=51) Yes (n=15) Yes (n=31) Yes (n=47) Figure 1. Flow chart of the selection sample process. Note: OA: osteoarthritis, FM: fibromyalgia, OA-CS: osteoarthritis with central sensitization, OA-noCS: osteoarthritis without central sensitization. Figure 1. Flow chart of the selection sample process. Note: OA: osteoarthritis, FM: fibromyalgia, OA-CS:The participants osteoarthritis signed with centralinformed consent sensitization, to accept OA-noCS: the conditions osteoarthritis without of the study. central We sensitiza- used a methodical and strict process that allowed us to ensure the sample strictly fulfilled tion. all the inclusion/exclusion standards; therefore, the sample was very well delimited. The finalThe sample (Table 1)signed participants was made up of 15 informed patients consent to with accept OAtheand CS (OA-CS) conditions aged of the between study. We 44 and used 81 (mean 66.37 a methodical and strict ± 8.77),that yearsprocess 31 with OA without allowed CS (OA-noCS) us to ensure the sampleaged between strictly 46 fulfilled and all (mean 66.8 years ±standards; the79inclusion/exclusion 7.39), andtherefore, 47 FM patients, without the sample wasfatigue chronic very well syndrome delimited. The agedsample final between 32 and (Table 63 made 1) was (meanup 46.47 of 15years ± 7.9) patients and with OAtheandpercentage CS (OA-CS) of aged low back pain between (86%), migraine (76.7%), and irritable bowel syndrome (48.8%) as other 44 and 81 (mean 66.37 years ± 8.77), 31 with OA without CS (OA-noCS) aged between 46 manifestations of central and sensitization 79 (mean 66.8 yearssyndrome. The 47 ± 7.39), and control group was FM patients, formed without of 22 participants fatigue with a chronic syndrome meanbetween aged of 51.56 years 32 and (±63 11.41). (mean This study 46.47 was±approved years 7.9) and by thethe Local Ethics percentage Committee of low and back pain was inmigraine (86%), compliance with and (76.7%), the Helsinki irritable Declaration. bowel syndrome (48.8%) as other manifestations of central sensitization syndrome. The control group was formed of 22 participants with a 1. Sociodemographic Table of mean 51.56 years (±11.41).andThis clinical characteristics study was approvedof theby sample. the Local Ethics Committee and was in compliance with the Helsinki Declaration. Groups Factors OA OA-CS OA-noCS FM Control N 46 15 31 47 22 Gender (women %) 71.7 84.2 65.9 100 59.3 Age (x(SD)) 66.67 (7.78) 66.37 (8.77) 66.8 (7.39) 46.47 (7.92) 62.92 (7.39) Months after diagnosis 55.28 50.58 57.46 84.38 - (x ± SD) (63.34) (54.09) (67.71) (54.14) Educational level (%) Uneducated 6.7 10.5 4.9 0 0 Primary education 21.7 26.3 19.5 10.6 26.9 Secondary education 15 10.6 17.1 21.3 12.1 General education 5 10.5 2.4 12.8 7.4 Int. J. Environ. Res. Public Health 2023, 20, 2935 5 of 13 Table 1. Cont. Groups Vocational education and training and/or 31.7 36.8 29.3 17 30.6 Higher education Bachelor and/or 20 5.3 26.8 38.3 23 University Degree Drug use (%) Painkiller 50 16 34 16 0 Non-steroidal Anti-inflammatory 51 16 35 17 2 drugs (NSAIDs) Antiepileptic drugs 2 0 2 4 3 Antidepressant drugs 14.9 15.8 19.5 85.7 7.4 Questionnaires 65.99 FIQ - - - (14.01) Mini-Mental: 27.61 26.82 (3.17) 28 (2.36) - 27.5 (2.45) (2.68) OA: osteoarthritis, OA-CS: osteoarthritis with central sensitization, OA-noCS: osteoarthritis without central sensitization, FM: fibromyalgia, SD: standard deviation, FIQ: fibromyalgia impact questionnaire, Mini-Mental: OA patients carried out cognitive screening because of their advanced age and the possibility of cognitive impairment. FM patients did not need it due to their age and study objectives. 2.2. Procedure First, patients attended rheumatologic visits where they were selected, and after verifying the inclusion/exclusion criteria as well as the will to participate, they were enrolled. During the next few days, patients attended psychological assessment, performed by the same clinical psychologist, which lasted about 90 min. Patients were visited twice in case of causing too much fatigue that may have influenced answers. The research only analyzes some aspects of this broad protocol. 2.3. Assessment Revised Temperament and Character Inventory (TCI-R) [28]: We administered the Spanish version of the TCI-R [29]. The original TCI-R is a 240-item personality self-report questionnaire, based on Cloninger’s multidimensional and psychobiological model that accounts for both normal and abnormal variations in personality. TCI-R assesses 7 per- sonality scales, each one with its own facets and a 5-point Likert response format (from 1 = definitely false to 5 = definitely true). All items are randomly listed and about half of them are reverse scored. The 4 temperament scales are: 1. Novelty-seeking (NS), defined as the inclination to respond impulsively to novel stimuli with active avoidance of frustration. 2. Harm-avoidance (HA) as the tendency to inhibit responses to aversive stimuli leading to avoidance of punishment. 3. Reward dependence (RD) as the predisposition to answer to signals of reward. 4. Persistence (PS) as the tendency to perseverance despite frustration and fatigue. The 3 character scales are: 1. Self-directedness (SD), which refers to the ability to control, regulate, and adapt behavior to fit the situation. 2. Cooperativeness (CO), which is related to acceptance of other people. 3. Self-transcendence (ST), which is viewed as the identification with everything con- ceived as essential and consequential parts of a unified whole. Int. J. Environ. Res. Public Health 2023, 20, 2935 6 of 13 The temperament facets in NS are: 1. Exploratory excitability (NS1), impulsiveness (NS2), extravagance (NS3), and disor- derliness (NS4). 2. HA: Anticipatory worry (HA1), fear of uncertainty (HA2), shyness with strangers (HA3), and fatigability (HA4). 3. RD: Sentimentality (RD1), openness to warm (RD2), attachment (RD3), and depen- dence (RD4). 4. PS: Eagerness of effort (PS1), work-hardened (PS2), ambitious (PS3), and perfection- ist (PS4). The character facets for SD are: 1. Responsibility (SD1), purposefulness (SD2), resourcefulness (SD3), self-acceptance (SD4), and enlightened second nature (SD5). 2. CO: Social acceptance (C1), empathy (C2), helpfulness (C3), compassion (C4), pure- hearted conscience (C5). 3. ST: Self-forgetful (ST1), transpersonal identification (ST2), and spiritual acceptance (ST3). Specifically, this inventory allows us to assess the possibility of the psychometric presence of some symptomatic personality disorders (histrionic, narcissistic, avoidant, antisocial, borderline, schizoid, and obsessional) if the scores of SD and CO are low or very low (17–33%). The lower cut-off point is situated in 35 points and the upper in 75. This questionnaire has proved to be reliable in its original version, with internal consistency alpha coefficients ranging from 0.65 for persistence to 0.89 for cooperativeness. The Spanish version also shows good estimates of internal consistency alpha coefficients, such as in our study except in the novelty-seeking scale (Table 2). Table 2. Percentile scores of temperament and character dimensions of TCI-R by group. Group OA-noCS OA-CS (n = 31) FM (n = 47) C (n = 22) K–W Test Cronbach’s TCI-R Dimensions (n = 15) Mean (SD) Mean (SD) Mean (SD) p Alpha Mean (SD) Novelty-seeking 45.58 (27.53) 39.00 (29.25) 36.21 (22.33) 43.68 (24.25) 0.379 0.43 Harm-avoidance * 53.61 (30.30) 43.80 (30.44) 85.85 (15.17) 43.27 (30.29) <0.001 * 0.77 Reward dependence 57.94 (22.80) 51.13 (24.62) 55.15 (27.89) 42.09 (32.94) 0.227 0.64 Persistence 39.03 (28.15) 50.8 (32.94) 41.13 (30.58) 42.05 (26.07) 0.675 0.77 Self-directedness 55.71 (28.03) 63.67 (31.40) 45.98 (30.27) 55.36 (29.63) 0.178 0.74 Cooperativeness 58.55 (30.84) 52.87 (32.39) 53.74 (27.88) 52.95 (29.05) 0.817 0.71 Self-transcendence 60.71 (30.03) 54.87 (35.32) 49.26 (30.07) 62.91 (32.82) 0.275 0.78 Note. TCI-R: Temperament and Character Inventory; OA-CS: osteoarthritis with central sensitization; OA-noCS: osteoarthritis without central sensitization; FM: fibromyalgia; C: control group; SD: standard deviation; K–W p: statistical significance of the nonparametric Kruskal–Wallis test; * statistically significant difference. 2.4. Data Analysis We performed nonparametric Kruskal–Wallis and chi-square statistical tests to analyze the differences between the four groups (OA-CS, OA-noCS, FM, and control group) in TCI-R mean percentile scores and in the distributions of the temperamental profiles and personality disorders of TCI-R, respectively. Logistic regression models were adjusted to identify the most characteristic personality pattern of these groups. For the statistical analysis we used the statistics Package SPSS 20 (SPSS Inc., Chicago, IL, USA). 3. Results Descriptive features of the final sample are shown in Table 1. Figure 2 and Table 2 show the mean percentile scores of the four groups of participants (OA-CS, OA-noCS, FM, and C) regarding both temperament and character dimensions of TCI-R. Most of the mean percentile scores ranged between the 40th and 60th percentile, but ysis we used the statistics Package SPSS 20 (SPSS Inc., Chicago, IL, USA). 3. Results Descriptive features of the final sample are shown in Table 1. Figure Int. J. Environ. Res. Public Health 2023, 20, 2935 2 and Table 2 show the mean percentile scores of the four groups of partici- 7 of 13 pants (OA-CS, OA-noCS, FM, and C) regarding both temperament and character dimen- sions of TCI-R. Most of the mean percentile scores ranged between the 40th and 60th per- centile, HA in but FM HA in FMwas patients patients was statistically statistically higher thanhigher than in the in the other other(pgroups groups (p