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Address correspondence to Kazuhiro Kimpara, Ph.D., School of Rehabilitation Sciences, Seirei Christopher University, 3453 Mikataha Kitaku, Hamamatsu, Shizuoka 433-8558, Japan.
School of Rehabilitation Sciences, Seirei Christopher University, Hamamatsu, JapanTerada Pain Clinic, Hamamatsu, JapanSchool of Rehabilitation Sciences, Seirei Christopher University, Hamamatsu, Japan
Catastrophic thinking among patients with chronic pain impairs their quality of life and increases anxiety levels. Further, severe pain causes high emotional brain sensitivity and unpleasant feelings. However, the effects of emotional changes on catastrophic thinking in patients with chronic pain remain unclear.
Aims
We hypothesised that emotional brain activity during mild pain stimuli would affect catastrophic thinking in these patients. We aimed to examine the relationship between unpleasant emotional brain activation and catastrophic thinking due to pain stimuli in patients with chronic pain.
Design
This was a prospective observational study.
Participants
We included patients with chronic pain and healthy individuals.
Methods
The impact of emotional brain activity on catastrophic thinking was evaluated, specifically, the skin conductance response and oxygenated haemoglobin levels using near-infrared spectroscopy. After receiving three different pain stimuli, the participants were evaluated using the Numeric Rating Scale, Pain Catastrophising Scale, and McGill Pain Questionnaire.
Results
There were 28 patients in the chronic pain group and 33 patients in the healthy group. There was no between-group difference in oxygenated haemoglobin levels during pain stimulation. The chronic pain group showed a higher Pain Catastrophising Scale score and skin conductance response than the healthy group (p < .05). In the chronic pain group, oxygenated haemoglobin levels after pain stimuli were significantly associated with the Pain Catastrophising Scale score and skin conductance response (p < .05).
Conclusions
Brain activity of unpleasant emotions may influence catastrophic thinking in patients with chronic pain.
Distinctive subgroups derived by cluster analysis based on pain and psychological symptoms in Swedish older adults with chronic pain—A population study (PainS65+).
Chronic pain patients can be classified into four groups: Clustering-based discriminant analysis of psychometric data from 4665 patients referred to a multidisciplinary pain centre (a SQRP study).
). Specifically, catastrophizing, which is characterized by helplessness, magnification, and ruminative thoughts regarding pain, is a potent predictor of negative pain-related outcomes (
The relationship of self-efficacy to catastrophizing and depressive symptoms in community-dwelling older adults with chronic pain: A moderated mediation model.
). Therefore, CP and catastrophizing could interact with each other and increase the total symptom burden, leading to greater challenges in the clinical management of patients with CP.
Compared with healthy individuals, people with CP present with unpleasant emotions, including strong fear and anxiety (
). Emotional brain activity influences pain catastrophizing and anxiety. However, the influence of emotional changes in people with CP on catastrophic thinking remains unclear. We hypothesized that increased emotional brain activity after pain stimuli would lead to catastrophizing in people with CP. Pain site stimulation may increase emotional activity to induce catastrophizing in people with CP undergoing pain management nursing. Accordingly, we aimed to examine the relationship between brain activities related to unpleasant emotions and catastrophic thinking due to pain stimuli in patients with CP.
Methods
Ethics Statements
This study was approved by an independent ethics committee at Seirei Christopher University (approval number: 10069) and registered with the University Hospital Medical Information Network Center (UMIN000045273, http://www.umin.ac.jp/). All participants provided written informed consent before study participation.
Study Design and Participants
This was a prospective cohort study of patients with CP (CP group) and healthy participants (healthy group). The participants were recruited between July 2012 and July 2013. Patients with CP and healthy individuals were recruited from the Terada Pain Clinic (Hamamatsu, Japan) and Seirei Christopher University (Hamamatsu, Japan), respectively. The inclusion criteria for the CP group were as follows: (1) confirmed CP by the clinician defined as pain in more than one anatomical region (chronic musculoskeletal pain type) that persists or recurs for 3 months or longer and is related to significant emotional distress or functional disability (
); (2) having experienced pain for 3 months or longer; (3) aged 20 years or older; and (4) having a weekly average pain rating of 4 or greater on a 10-point Numerical Rating Scale. The inclusion criteria for the healthy group were as follows: (1) no history of pain or disease; (2) not currently taking analgesic medications; and (3) aged 20 years or older. We excluded healthy people who used medications that affect autonomic nervous system activity. Further, we excluded patients with CP who used medication that affected the autonomic nervous system activity (e.g., beta blocker, catecholaminergic agent, and Levodopa) or were unsuitable for physical pain stimulation due to severe disease (e.g., patients with Parkinson's disease, cerebral vascular disease, and ischemic heart disease).
Protocol
On the first visit, all participants received explanations regarding the study. On the second visit, the participants received three different electrical pain stimuli using a chronaxie meter (CX-3 OG; Giken, Tokyo Japan), which produced an electrical stimulus of 2.1 mA (stimulus duration, 0.3 ms at 1 Hz) on the palm side of the right forearm (Fig. 1). The pain stimuli were characterized by a tingling sensation with moderate intensity (the intensity at which a healthy adult usually feels a little pain). The participants were allowed to rest for 300 seconds and received three pain stimuli (1 s each) at 60-second intervals (Fig. 1). The chronaxie meter has confirmed validity and reliability for ethical use in pain research. Specifically, a previous Japanese study confirmed the safety of pain stimulation using a chronaxie meter with approximately the same stimulus and intensity (
). Near-infrared spectroscopy (NIRS) was performed and the skin conductance response (SCR) was measured during the resting period and three pain stimuli to evaluate the transmission of pain stimuli to the limbic system. Pain stimuli transmission to the limbic system stimulates emotions and memory in the amygdala and hippocampus before transmission to the prefrontal cortex (
). The SCR was measured using a biologic polygraph recorder (MP100; Biopac Systems, Inc., Goleta, CA). After pain stimulation, the patients were asked to complete the Numerical Rating Scale, Pain Catastrophizing Scale (PCS), and McGill Pain Questionnaire. The experiment room was maintained at a comfortable temperature (26.1 ± 0.6 °C).
Emotional brain activity in the prefrontal cortex was evaluated based on oxygenated hemoglobin (Oxy-Hb) using NIRS (optical topography device, ETG-7100; Hitachi, Ltd., Tokyo, Japan). NIRS is suitable for cerebral cortical measurements at a measurement depth of 2 to 3 cm. NIRS has a higher temporal resolution than functional magnetic resonance imaging (fMRI) (
Deactivation and activation of left frontal lobe during and after low-frequency repetitive transcranial magnetic stimulation over right prefrontal cortex: A near-infrared spectroscopy study.
Quantitative evaluation of deep and shallow tissue layers' contribution to fNIRS signal using multi-distance optodes and independent component analysis.
). Accordingly, NIRS measurements have good reliability and validity.
The NIRS probe was placed on the head based on the international electroencephalography 10-20 method; further, Oxy-Hb and deoxyhemoglobin levels were measured at all 47 channels (sampling frequency, 10 Hz). We used the number 5 channel, the Brodmann Area 10, which recognizes unpleasant emotions. We used NIRS to measure activity in the orbitofrontal cortex, which is responsible for emotional perception in Brodmann Area 10. We calculated the difference in Oxy-Hb representative data averaged for 10 seconds before and after pain stimulation.
SCR
SCR measures mental sweating of the palms and feet bottom. The central mechanism of mental sweating mainly involves the limbic system and hypothalamus (
). The SCR does not reflect the actual sweating amount; instead, it evaluates perspiration activity as the electrical potential. Accordingly, SCR measurements have good reliability and validity. We calculated the difference in SCR representative data averaged for 10 seconds before and after pain stimulation.
Patient-Reported Outcomes
The patients completed the Numerical Rating Scale, PCS, and McGill Pain Questionnaire after the pain stimulation.
Numerical Rating Scale
Pain intensity was assessed using a 10-point Numerical Rating Scale [0 (‘no pain’), 10 (‘worst imaginable pain’)]. The Numerical Rating Scale is well correlated with the visual analog scale (
), which indicates the reliability of Numerical Rating Scale measurements.
PCS
The PCS measures catastrophic thinking, which is an emotional and psychological state in people with CP. We assessed pain catastrophizing using the Japanese version of the PCS (PCS-J) (
). It comprises 13 items that are scored to provide an overall composite catastrophic measure; further, it has three subscales representing rumination, magnification, and helplessness. Each item is rated on a 5-point Likert scale ranging from 0 (not at all) to 4 (all the time). The validity and reliability of the PCS-J have been demonstrated (
The McGill Pain Questionnaire is a self-report questionnaire that assesses the quality and intensity of subjective pain. It provides the total score of four categories using 78 descriptive words for pain (sensory, emotional, evaluative, and miscellaneous factors of pain). Further, it has been shown to be useful and reliable for patients with high psychogenic factors (
All data are presented as mean ± standard deviation (SD). Between-group differences in outcome measures were assessed using unpaired t tests. Further, the correlations of Oxy-Hb levels during pain stimulation with other measurements were assessed using Pearson's correlation analysis. Statistical analyses were performed using SPSS 24.0 for Windows (IBM Corp., Armonk, NY). Statistical significance was set at p < .05.
Results
Initially, there were 29 and 33 participants in the CP and healthy groups, respectively. We excluded data from one patient with CP due to missing values. Finally, we included 28 patients with CP and 33 healthy individuals (Fig. 2). Table 1 presents the demographics of the included participants. All participants in the CP group had diagnoses of chronic musculoskeletal pain and had multiple musculoskeletal pain sites.
Oxy-Hb levels were negatively correlated with the PCS score and SCR in the CP group (p < .01) but not in the healthy group (Figs. 3 and 4). Oxy-Hb levels were significantly associated with McGill Pain Questionnaire scores in both groups (Table 2).
Figure 3Correlation between SCR and Oxy-Hb at pain stimuli in the chronic pain group and healthy group. Oxy-Hb = Oxygenated Hemoglobin; SCR = Skin Conductance Response.
Figure 4Correlation between PCS and Oxy-Hb in the CP group and healthy group. PCS = Pain Catastrophising Scale; Oxy-Hb = Oxygenated Hemoglobin; CP = Chronic Pain.
The CP group showed a significantly higher SCR than the healthy group (p < .05) (Table 3). There were no between-group differences in the Numerical Rating Scale and McGill Pain Questionnaire scores (Table 4). The CP group showed significantly higher PCS scores than the healthy group (p < .05). There was no significant correlation between the PCS and age in both groups. Further, there were no between-group sex differences.
To our knowledge, this is the first study to evaluate the association between the PCS score and emotional brain activity due to pain stimulation in patients with CP. Our findings showed that the brain activity of unpleasant emotions during pain stimulation correlated with catastrophizing in patients with CP, which confirmed our hypothesis. However, there was no between-group difference in the NIRS findings. In the CP group, the NIRS findings were correlated with the SCR and PCS score; further, the neurophysiologic responses were correlated with limbic system activity (SCR) and orbitofrontal cortex activity (NIRS). Long-term pain may have sensitized the central nervous system in patients. Furthermore, in the CP group, the PCS score was correlated with the NIRS findings but not with the SCR. This further indicates that patients with CP may have developed a brain network related to catastrophic thinking due to long-term pain.
In the CP group, brain activation of unpleasant emotions at moderate pain intensity correlated with severe catastrophic thinking, as measured by the PCS.
reported that the PCS score was significantly related to anxiety and depression in 6,611 older adults. They reported that anxiety and depression were emotional distresses that should be addressed in the pain management of older adults with CP. Anxiety and depression are considered unpleasant emotions, which were reported by
The relationship of self-efficacy to catastrophizing and depressive symptoms in community-dwelling older adults with chronic pain: A moderated mediation model.
to affect catastrophizing and impair self-efficacy in 664 older adults with CP. They measured unpleasant emotions using patient-reported outcomes; contrastingly, we measured brain activation of unpleasant emotions with pain stimuli using NIRS, which yielded new findings in the research field. We found that Oxy-Hb levels in the emotional region were negatively correlated with the SCR in patients with CP. The SCR represents the variance in emotional ratings evaluated from the limbic system (
). The negative response related to Oxy-Hb levels was lower in brain activities with stimuli than in those without stimuli; moreover, it influenced the increased limbic cortical activity (high SCR). We found that moderate pain stimulation in patients with CP led to emotional activation in the cerebral cortex and limbic system. Decreased Oxy-Hb levels lead to low blood flow in the pleasant and unpleasant emotional regions. People with CP may experience a shift toward unpleasant emotions rather than pleasant emotions. Furthermore, the SCR is negatively correlated with the Oxy-Hb response in the emotional region. These findings show that patients with CP recognize low unpleasant emotions as highly sensitive to pain. Patients with CP have an elevated SCR and decreased blood flow in the emotional area due to central sensitization resulting from chronic pain exposure (
reported that the SCR with heat pain stimulation was negatively correlated with activity in the contralateral medial prefrontal cortex as measured through fMRI in healthy individuals. Since their painful stimulus was higher than ours (Numerical Rating Scale score, 6.1 versus 4.9), a correlation was observed even in healthy participants. A previous study showed that patients with CP experienced weak pain stimuli strongly; accordingly, patients experienced pain stimulation at a Numerical Rating Scale score of 4.4 as strong pain in the prefrontal cortex (
reported that the SCR to cold pain stimuli was higher than that at rest in 120 participants with CP. Individuals with low back pain have poor sleep quality and an increased SCR, with these parameters being correlated (
). Sleep quality in individuals with CP may have influenced our results. The SCR represents limbic cortex activity, including emotion in the amygdala and insula, which has a high sensitivity to pain (
). Central sensitization is characterized by the hyperexcitability of central nervous system neurons to noxious stimuli and involves multiple somatosensory processing changes (
). People with CP experience severe pain due to high central sensitization; moreover, the SCR of the amygdala and insula is increased during unpleasant emotion processing (
The response of Oxy-Hb levels in the emotional region to moderate pain was significantly related to the McGill Pain Questionnaire score in both groups.
reported that depression and the McGill Pain Questionnaire score in patients with low back pain are closely related to activity in the dorsolateral prefrontal cortex based on fMRI findings. Most patients with CP develop depression; accordingly, there is a need to elucidate the influence of depression on prefrontal cortex activity. We previously reported that pain catastrophizing and anxiety were significantly improved after watching relaxation videos and dual-task training in people with CP (
). Accordingly, pain management nursing care targeting pleasant emotions may improve catastrophic thinking in people with CP.
Limitations
This study has several limitations. First, this was a single-center study on patients of a single race with preserved functionality, which limits the generalizability of our findings. Second, we did not match the age between the CP and healthy groups. The healthy group had relatively young participants since they lacked a history of pain or disease. Third, we did not evaluate brain activation using fMRI. Fourth, the sample size was not sufficient to evaluate between-sex differences. Differences in age and sex in both groups may influence pain catastrophizing. Finally, we did not evaluate the effect of pain rehabilitation and pharmacologic therapy in patients with CP.
Conclusions
In conclusion, we clarify that unpleasant emotional brain activity due to pain stimuli is associated with catastrophic thinking in patients with CP. The brain activity of unpleasant emotions is a crucial factor in the brain plasticity changes responsible for catastrophic thinking. Our findings indicate that treatment strategies for decreasing unpleasant emotions are important for people with CP.
References
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Brain moderators supporting the relationship between depressive mood and pain.
Chronic pain patients can be classified into four groups: Clustering-based discriminant analysis of psychometric data from 4665 patients referred to a multidisciplinary pain centre (a SQRP study).
The relationship of self-efficacy to catastrophizing and depressive symptoms in community-dwelling older adults with chronic pain: A moderated mediation model.
Quantitative evaluation of deep and shallow tissue layers' contribution to fNIRS signal using multi-distance optodes and independent component analysis.
Deactivation and activation of left frontal lobe during and after low-frequency repetitive transcranial magnetic stimulation over right prefrontal cortex: A near-infrared spectroscopy study.
Distinctive subgroups derived by cluster analysis based on pain and psychological symptoms in Swedish older adults with chronic pain—A population study (PainS65+).
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