Patients’ experiences of treatment-relevant processes in multimodal pain rehabilitation for severe complex regional pain syndrome – a qualitative study

Abstract Purpose Complex regional pain syndrome (CRPS) is a longstanding condition with spontaneous and evoked pain, that usually occurs in an upper or lower extremity. Although it often resolves within the first year, it may for a minority progress to a chronic and occasionally severely disabling condition. The aim of this study was to explore patients’ experiences and perceived effects of a specific treatment, designed for patients with severe and highly disabling CRPS, in order to identify possible treatment-relevant processes. Methods The method used was a qualitative design, using semi-structured interviews with open-ended questions to capture participants’ experiences and perceptions. Ten interviews were analyzed using applied thematic analysis. Results Despite the fact that participants had a severe conditions, including nerve damage and a long duration of illness, they reported having been helped to increase flexible persistence, reduce fear and avoidance, and improve connections. This helped participants to significant improvements in daily life functioning. Conclusions The participants described distinct possible treatment-relevant processes leading to a substantial improvement in everyday life. The results imply that there is hope for this group that has been severely disabled for many years. This may help guide future clinical treatment trials. IMPLICATIONS FOR REHABILITATION Flexible persistence, i.e., to lead a life more in line with personal values, despite pain and limitations, seems to be an important theme in the treatment for complex regional pain syndrome (CRPS). Acceptance-based exposure treatment can be helpful in reducing fear and avoidance behaviors. Both improved social connections and increased self-connection may be highly valuable in CRPS rehabilitation.


Introduction
complex regional pain syndrome (cRPs) is a longstanding condition with spontaneous and evoked pain that occurs most frequently after fracture, often being resolved within the first year, but may for a subset progress to a chronic and sometimes severely disabling condition [1,2].cRPs usually occurs in an upper or lower extremity after minor or major trauma or surgery [3,4], but can become more widespread and affect multiple parts of the body [5]. the symptoms are primarily characterized by severe continuous pain with skin hypersensitivity to mechanical and thermal stimuli, peripheral autonomic and trophic disorders, and motor and sensory changes [6].Many individuals with chronic conditions develop body perception disturbance [7].
cRPs is historically classified into two subcategories: cRPs type 1, without detectable nerve damage, and cRPs type 2, where nerve damage has been detected [8].Recently, a third subgroup has been introduced, cRPs-not otherwise specified (cRPs-NOs) [9].however, the clinical implications of these subgroups are unclear, and may not affect the treatment regime [9]. the underlying pathophysiology is not fully clarified, but it has been suggested that there is an interplay of several factors in both the onset and maintenance of the condition [8].
longstanding cRPs can be a challenging condition to treat, and though, e.g., functional restoration has been considered critical, research data for most cRPs interventions is modest and more research is warranted [10].Nevertheless, interdisciplinary treatment based on a biopsychosocial approach is generally recommended [11].although only a few studies have explored the relationship between treatment processes and positive outcomes, it has been proposed that including exposure-based treatments, and interventions aiming to foster acceptance, may be of great importance in the rehabilitation of longstanding pain in general [12] , and in the treatment of cRPs [13].
it is reasonable to assume that avoidance of activities that trigger pain has a protective function against acute pain [14].Fear of movement is strongly correlated with protective behaviors such as guarded movement, i.e., movement patterns and posture adapted to the pain [15].however, such avoidance behaviors may lead to inactivity and, in the long run, disuse, e.g.physiological changes such as muscle hypotrophy, decreased cardiovascular endurance and decreased neuromuscular coordination [16,17].several of the symptoms seen in cRPs could in fact, at least in part, be explained by disuse after immobilization of the affected extremity due to pain or fear [16][17][18].Furthermore, an association between cRPs symptoms and cortical reorganization, i.e., changes in sensorimotor processing that may maintain symptoms, has been suggested [19][20][21][22][23], but research data is inconsistent [24,25].
in recent years, there has been an increase in the interest of developing and including acceptance-based interventions in rehabilitation for chronic pain, where the focus shifts from controlling and avoiding pain to accepting it [26].a goal is that patients increase their willingness to stay in contact with, e.g., fear and unwanted physical sensations, in order to lead a more fulfilling life [27].several behavior change procedures known from traditional cognitive behavioral therapy (cBt), e.g., exposure therapy, are part of acceptance-based treatment protocols, but with a different function [28]. in cognitive-behavioral in vivo exposure to treat pain, individuals with long-term pain and a high degree of fear and avoidance are exposed to the movements and activities they avoid, in order to regain functional behaviors [29].such treatment has been shown to reduce fear and disability, as well as pain intensity and physiological symptoms in cRPs type 1 [30].While traditional cognitive-behavioral approaches emphasize symptom reduction and the modification of unhelpful cognitions as processes of change in exposure therapy [31], exposure-based methods, framed as acceptance-based interventions, promote openness to unwanted experiences, e.g., anxiety or pain, defusion from cognitions, and engagement in valued activities [26].
a reduction in pain behavior following exposure may also affect pain-related processes in the central nervous system [32].Moreover, interventions such as mirror training and sensory stimulation, targeting motor and sensory representation, have been suggested to alter a proposed cortical reorganization [33].however, there is limited evidence that sensorimotor changes cause symptoms, as well as that treating sensorimotor conflicts can reduce symptoms [23].chronic cRPs may be a challenging condition to treat, and there are few interventions with clearly demonstrated effects [10].Due to its complexity, a multimodal treatment approach is warranted [34].however, research on multimodal treatment programs for cRPs is sparse [35], and their effect remains to be proven [10].it has been suggested that early interventions are crucial to prevent chronic disability, and there is a gap in the research literature about the possibilities for positive treatment outcomes once the condition has become longstanding [13,36].
to our knowledge, no interview studies with patients on their experiences of multimodal treatment for severely disabling cRPs have been reported.in this study, we applied a qualitative approach with semi-structured interviews, allowing the participants to express their opinions, experiences, and feelings in their own words [37], with an understanding of experiences and perceptions being prioritized [38].
More research regarding cRPs interventions is necessary [10], and studying specific themes in multimodal cRPs treatment for individuals with longstanding conditions could be one way to increase knowledge.the aim of this study was to explore severely affected patients' experiences of a specific, multimodal, person-centered treatment for longstanding and disabling cRPs, in order to increase our understanding of which specific themes, if any, contributed to any changes in their condition and everyday life.

Setting and recruitment
Based on previous studies [30,39], a specific multimodal treatment has been designed for individuals with severe cRPs type 1 or 2. the program is described in detail in table 1. the patients participating in the treatment program typically have very severe symptoms of long duration that have been refractory to numerous different treatments, including multimodal pain rehabilitation programs.
Table 1.an overview of the treatment program.

Frames
Patients from various parts of sweden were included in an in-hospital treatment program.all patients were diagnosed with CRPs type 1 or 2 in accordance with the budapest criteria.the treatment took place during the course of four weeks, supplemented with an additional four-week treatment period if necessary.overview the treatment was based on a multimodal model, individually adapted based on each patient's avoidance behaviors and in line with important personal values, i.e., the goals and desires one cares about most deeply (e.g., being a supportive parent).this took place within an acceptance-based framework which included group sessions, described in greater detail below.exposure treatment the exposure treatment took place daily during the treatment weeks, with the help of a psychologist and a physiotherapist.the aim was to increase the possibility for values-based actions, and to foster pain-related acceptance, rather than decreasing symptoms.in addition, graded physiotherapy training was given, specifically targeted at the physical deconditioning from long-term immobility.occupational therapy interventions were performed to improve the patients' impaired functional abilities in everyday activities.interventions targeting cortical reorganization Mirror training (creating a visual illusion of a normal functioning limb), de-sensitivity training (touching the affected body part with gradually more "difficult" materials), and sensory re-learning (practicing the ability to feel and distinguish between different stimuli), were used to target a possible cortical reorganization.Group sessions the patients also participated in about 15 group sessions on the ward, together with other in-patients with complex pain.these group sessions were based on the acceptance and commitment therapy (aCt) model.aCt is a form of cognitive behavioral therapy that includes acceptance strategies and mindfulness meditation.the purpose was to create psychological flexibility where the patients learned to be in contact with thoughts, sensations, and feelings that were experienced as unpleasant, instead of focusing on controlling or eliminating pain or other symptoms.lastly, a family day was held where next-of-kin could participate during parts of the treatment, receive information about the pain condition, and exchange experiences with other people who were next-of-kin to patients.
CRPs: complex regional pain syndrome.
all patients diagnosed with cRPs type 1 or 2 at the beginning of treatment, who underwent the pain rehabilitation program during 2012-2020, were invited to participate in this study.the content of the program was unchanged during this period.Written information about the study and a consent form were sent by post to all potential participants, and they were also contacted by phone.Written and verbal consent was obtained from all participants.the study was approved by the swedish ethical Review authority (DNR 2020-03383).the Budapest criteria (2003) was used to diagnose cRPs and thus served as inclusion criteria [40,41].

Interviews
semi-structured interviews with open-ended questions were conducted, based on an interview guide developed by the research team [42].Questions concerned the participants' experiences of the treatment and how they perceived their present status.Probing was used if clarification was needed.the interviewer recurrently recapped the participants' thoughts and opinions to make sure they were correctly understood.the interviews were held over the phone, recorded with a digital voice recorder and transcribed verbatim.each interview session lasted between 14 and 51 min (median 32 min).all interviews were included in the analysis.the interview guide is included in appendix 1.
all interviews were carried out by author cJ. the analysis was performed by authors cJ and cN.cJ is a senior medical student with a special and personal interest in cRPs.cN is a researcher experienced in psychiatry and qualitative research methodology.there were no pre-existing relationships between participants and the interviewing researchers.Neither cJ nor cN had been involved in the treatment of the participants.We discussed within the research group whether the authors' pre-understanding affected the interviewing or the interpretation of the results, but deemed it unlikely that this affected the interviews or analysis in any confounding way.

Data analysis
the interview data were analyzed using applied thematic analysis [43].applied thematic analysis draws from a broad range of several theoretical and methodological perspectives.its primary concern is with presenting the participants' thoughts and experiences as accurately and as comprehensively as possible.themes were identified and analyzed inductively, i.e., themes were formed from data only and not from predetermined hypotheses.
the analysis was performed step by step: 1) the transcripts were read several times by authors cJ and cN independently of each other.2) Words, sentences, and potential patterns of interest and importance relative to the study aim were identified and coded.3) the codes were sorted into preliminary themes.4) the authors re-read the materials, after which new themes were created and existing ones were reviewed.the two authors had discussions throughout each step of the process.the analysis continued until each individual theme was clearly defined and reflected the contents in a representative way.see table 2 for examples from the thematic analysis process.

Results
Out of a total of 16 patients who had undergone the program, ten were included in the study.three of the 16 declined, two could not be reached, and one had died.the ten participants are described in table 3.

Status at the time of the review
None of the participants was in complete remission at the time of the interviews, and a majority of them said that they still had persistent pain.however, many participants stated that the treatment had led to great improvements in the management of the condition and everyday life, and thus had increased their quality of life.some reported major functional gains, e.g., being able to walk again after being wheelchair-bound for many years.
in the analysis of the interviews, three primary themes regarding treatment components were identified: 1) Flexible persistence, 2) reduced fear and avoidance, and 3) increased connection.
Theme 1: Flexible persistence the participants described the treatment as having helped them to reach acceptance of their condition.in the program, they learned to adjust to difficult situations and lead a life more in line with their personal values, despite the pain and limitations that the condition entailed in everyday life.Participants described having changed their way of thinking in that they no longer allowed pain to be the primary part of their everyday life.
"I think a little differently about the pain I have.You have accepted it more and try to move a little more even though it hurts."(#7) some had learned to direct their attention to stimuli other than the pain, e.g., to focus their senses on scents in the air or birds flying around when they were out in nature.Others had come to use goals and sub-goals as an important strategy or had stopped taking all their medications in order to think more clearly and deal with the pain more consciously.their changed strategies helped them do the things they wanted to do, even in the presence of pain.

"I also think that the treatment as such encourages you to try to do what you long to do. You had to learn to take the pain with you, instead of thinking that I will do this when I have less pain, which hasn't happened in 25 years." (#8)
Participants described having learned to stay and, e.g., "breathe through the pain," rather than try to escape from it.
"I use that a lot.Just breathing and concentrating and not trying to escape the pain.Because I think I did that before.You try to leave it behind, but you can't get away from it.It's like an annoying kid drawing my attention." (#9) Gaining more knowledge about their condition from a scientific perspective emerged as one important factor that helped them reach acceptance.
"You learned what chronic pain is and why you have it.This is something I had wondered about before, but I didn't get any answers.No help, so I didn't know why it's like this.But now I know."(#6) individual variations in expectations prior to the treatment may have affected the outcome: two participants with positive treatment outcome said that they saw the treatment as a chance for change and that they had entered into the program with a positive and open mindset.One participant was reluctant to participate in the treatment and later stated that it was of no help.

Theme 2: Reduced fear and avoidance
Participants reported that the treatment led to a reduced fear of the perceived pain and of different situations that could increase the pain and initiate a pain breakthrough.By practicing not to avoid possibly painful situations, they reported having managed their fear of such situations in a more constructive manner.
"Not be so afraid and protect the part I have pain in.To dare a little more.For me, it's a big difference… To dare to go close to the border and not be so scared."(#4) some of the participants were no longer afraid of being among people.Previously, they had avoided such situations due to fear of increased pain if someone happened to touch their cRPs-affected limb.

"Now I'm not terrified when I'm among people and things like that either. " (#5)
as a result of reduced fear and avoidance, participants dared to be more physically active even though they were in pain.

"I experienced when I came to Uppsala that I had a hard time being among people. I protected my foot so much then. Before I went into the treatments, I did not go out. I sat in the car if we were going out shopping or going into the supermarket. But now I can go out!" (#4).
Due to the treatment, several of the participants reported that they now dared to touch their affected extremities, which was previously unthinkable.For example, one participant had previously been placed under anesthesia in order to receive foot care.With the help of the exposure treatment, she became able to put cream on her foot daily and she even allowed family members to touch it.some participants described that exposure treatment made it possible for them to shower again.Others said that they can now use new clothes and shoes.One was even able to have children or dogs in her lap, which had previously been impossible.

"I've learned to be touched on my leg in a different way through the treatment we had (…) I can have children or a dog on my lap, before they had to sit on only one of my legs and it was very hard for my grandchildren, they had grown up sitting on one leg and then I suddenly said 'you can sit on both now.'" (#7)
the support from the treatment team was of great importance for making progress by daring to subject oneself to feared movements and activities during the treatment.the support from the psychologist was repeatedly mentioned to be of particular importance.

Theme 3: Increased connection
Participants reported that the treatment had contributed to an increased self-connection, i.e., a better understanding of their condition, values and needs.they described how they had started to prioritize activities in line with their values, rather than always trying to do everything they believed others expected from them.

"I've learned my limitations. That I can't go 100% of the time, I have to choose a little more in everyday life what I can do that day. I have to prioritize what's important and not do everything I want." (#6)
Moreover, the treatment had led to improved social connections.they perceived a lot of understanding from the treatment team, their fellow patients, and their significant others.Many had previously felt lonely due to their condition and that others, including health care professionals, did not really understand them.

"I've felt alone in this condition for a very long time. (…) Not being listened to and not being believed all the time, but getting the confirmation that you are right. This isn't something you have made up. These are normal symptoms of this disease. It's been very nice to get that confirmation, that it's not me being crazy, there is a diagnosis like this." (#6)
however, one of the patients did not feel understood by the treatment team, and did not gain from treatment.

"I had a feeling that I was not really believed in. That they didn't really listen to what I had to say. I was so much more than what my caregiver heard and listened to. I thought they missed quite a big part of me. " (#3).
several of the participants described it as a very important and positive part of the treatment to meet others with the same CRPs, complex regional pain syndrome.
diagnosis in order to exchange experiences.in particular, they mentioned the feeling that someone really understood them.
"That was absolutely the greatest part of it all, I think.Getting to know people, really making friends who understand exactly how you feel or you can share experiences and things like that.Tips and ideas for each other.I think that was really the most beneficial aspect."(#5) Participants pointed out that the family day was of great importance.the information given on that day contributed to their next-of-kin gaining an increased understanding of their condition and the limitations that the condition entailed in everyday life.

"What I think is good, and what has really helped the whole family, was that the next-of-kin got to come to a day of lectures and were present during my exercises. (…) My husband also got to attend a lecture about what this pain is and what it means to live with this pain. He gained more insight into my everyday life and how I feel. It's helped us a lot, he is more understanding when I can't handle things at home. I think that has been great." (#7)
Discussion and conclusions the present study provided an insight into patients' experiences of a treatment program for severe longstanding cRPs when they were allowed to express their feelings and thoughts in their own words.the participants were severely disabled by their condition and had not responded to other treatments.the subjects' experience of the treatment program was that it contributed to a significant improvement in daily life functioning, despite the long duration of illness, up to 18 years, and despite a majority being diagnosed with cRPs type 2. however, no participants became symptom-free, and three patients reported worse pain.
the prognosis and outcome of cRPs vary, but patients seem to have a better chance of improvement early in the course of the condition [44,45].Patients with cRPs type 2 may have more extensive injuries due to detectable nerve damage, which could hypothetically mean that they will find it harder to fully recover, not least when it comes to pain levels.however, the present study indicates that major treatment gains can be reached even after many years, and it did not show any obvious differences between the two subgroups.thus, the results indicate that there is hope, even for this group that did not recover initially and that has been severely disabled for many years.
Perhaps one of the most notable findings was that, regardless of the fact that these patients were severely affected by longstanding and very disabling cRPs 1 or 2, the treatment processes variables identified as important in the interviews, in part, mirror those in individuals with other forms of longstanding pain [12], see Figure 1.
the participants in our study stated that the treatment led to an acceptance of their condition and pain.as they learned to accept their condition and find meaning in life, despite their pain and limitations, they experienced that their quality of life increased.

"I have a completely different rich life even though I have my pain. (…) I am extremely grateful that you have this program.
Because it has changed my quality of life."(#8) in previous studies of pain treatment outcomes, acceptance has been found to be an important factor and acceptance and commitment therapy (act) being seen as a promising treatment for longstanding pain [46] Participants described that they had changed their way of functioning, started doing the things they valued despite the presence of pain, and were no longer allowing pain to be the primary aspect of their everyday life.this shift to "flexible persistence" seems to fall within the behavioral repertoire that characterizes "psychological flexibility, " that is, to persist with, or adapt, behaviors that are in line with one's personal values, regardless of unwanted thoughts, negative emotions, or aversive physical sensations.Psychological flexibility is the core goal of act [47], and research has shown this flexibility to have a mediating role in relation to treatment outcomes [48].Our results, based on the patients' own words, supported some of those findings, even in the severely disabled group included here.
Gaining knowledge about the condition gave the participants an increased understanding, which they considered important for reaching acceptance and reducing fear. in cBt, cognitive understanding of one's condition is considered to be a core element of successful treatment [49].together with an increased understanding of their condition, exploring values and needs led to an increased self-awareness and self-acceptance.this kind of improved self-connection have been suggested to facilitate flexible persistence, making behavioral decisions out of one owns preferences and values, rather than avoidance of unwanted experiences [50].
another important factor reported in this study was the feeling of being understood in the meeting with other cRPs patients.seeing similar problems in others and how others deal with them is a type of peer support that forms the basis for numerous kinds of self-help groups.it has previously been found that patients with chronic pain can benefit from participating in support groups, with the exchange of personal experiences being seen as valuable [51].For example, participating in a cRPs peer support group online contributed to emotional and social support, which in turn helped participants re-engage with the outside world [52].the Figure 1. an illustration of the participants' experiences of the treatment and its results.CRPs: complex regional pain syndrome family day was considered to be an important part of the treatment.Perceived support from significant others is known to affect the outcome of rehabilitation in patients with other forms of longstanding pain, resulting in significantly less reliance on medication, decreased pain intensity, and increased levels of activity [53].
Participants reported that the treatment resulted in reduced fear of pain.this factor seemed to make an important difference in their everyday lives.high level of pain-related fear has been shown to be related to less improvement following treatment and, thus, has been suggested to be an important treatment target variable [54]. in a randomized controlled trial by den hollander and co-workers, patients with cRPs type 1 with moderate to high pain-related fear were randomized to two different treatments.One group received exposure therapy and the other received treatment as usual.the exposure treatment was superior to treatment as usual and resulted in increased quality of life, reduced pain catastrophizing, reduced pain intensity, and reduced perceived harmfulness of activities [55].similar positive effects were described by the participants with long-standing cRPs 1 or 2 in the present study.Den hollander and colleagues have also showed that exposure to a diversity of activities, rather than repeated exposure to the same activities, are favored to reduce pain catastrophizing and fear of movement [56].Furthermore, a recent narrative review concludes that, even though there is a need for high-qualitative studies, the available data have not showed any risk for major harm due to exposure-based interventions for individuals with cRPs [57].almost all participants had severe cRPs symptoms when entering the program and reported having been helped by the program.it is possible that the combination of methods and the intensity and duration of the program, with daily treatment for four full weeks, were important factors in this.Further, individual motivation and expectations may be of importance for the outcome.some of the participants mentioned that they wanted to give the program a serious try, even though it might be demanding.they described it as a final chance to come to terms with their cRPs.however, as noted above, one of the participants was reluctant to participate and did not feel that the treatment team understood her, and later did not feel that she had been helped.even though some of the participants mentioned that the interventions targeting cortical reorganization were helpful, it was not identified as a treatment-relevant process on its own, which may reflect a lack of perceived effect for the majority.this could be considered to be in line with the doubt of the concept that has arisen with the MRi data [24,58], although a recent systematic review suggested that adding mirror therapy to conventional treatment may result in improvements in disability [59].
lastly, the multimodal organization of the program was appreciated by the participants.Previous studies suggest that this has been an important strategy in the treatment of other forms of chronic pain [60][61][62][63].

Strengths and limitations
the major strength of this study is that it was performed in a clinical setting and with a qualitative method that allowed participants to express themselves in their own words.another strength is that the interviewer and interview analysts were not involved in daily treatment, which reduced the risk of positive outcome bias from care providers.
an obvious limitation is that some of the participants attended treatment many years ago, and it may have been hard for them to remember details about the process, and the positive results they reported may have been influenced by factors other than the treatment.however, the congruence in the themes reported would indicate that they reflect important processes directly affected by the treatment.another limitation is that the acceptance-based group sessions, that the subjects participated in, were not exclusive to cRPs patients, and other individuals with longstanding and severely disabling pain attended the same sessions.
in conclusion, the study showed that this multimodal in-hospital treatment was generally experienced as having a positive effect by patients with severe symptomatic cRPs, who had previously been "resistant to treatment, " often for many years.For the majority of participants, the treatment led to increased psychological flexibility and reduced fear of pain.they also gained an understanding of their condition and a feeling of being understood.Participants described major functional improvements and improved everyday life with increased quality of life after the treatment.hence, including the treatment process variables identified in future clinical studies may help increase our understanding of how to best design treatments for this often severely disabled group.

Table 2 .
examples from the thematic analysis process.
"Íve changed the direction of my thoughts, i just decide what i want to do." (#8) Changed mindset Flexible persistence "X put his hand on my foot, that was a bit tough and i almost got angry with him."(#4) exposure to fearful situations Reduced fear and avoidance "i really appreciated talking to others and hearing their experiences."(#6) learning from others increased connection

Table 3 .
Description of the participants.