慢性痛形成のメカニズムとして, 抑うつ・破局的思考・運動恐怖によって, 痛みの難治化・遷延化を招く悪循環モデル(恐怖回避モデル)が提唱されている。さらに, 慢性痛患者は, 痛みからの解放を求め, 必ずしも適切ではない医療・療法を衝動的に受け入れることによって, 身体的・心理的・経済的疲弊を招く。本研究は, 慶應義塾大学医学部倫理委員会の承認を受けた後, 慢性痛の心理行動学的特徴のなかで, 恐怖回避思考と衝動性に着目し, それらの心理行動が, 脳機能に及ぼす影響を, 安静時機能的磁気共鳴画像(fMRI)を用いて解析した。慶應義塾大学病院の麻酔科外来に通院中の慢性痛患者20名および年齢・性別を適合させた痛みのない健常者20名を対象として, 質問票を用いて慢性痛の程度, 運動恐怖(Tampa Scale for kinesiophobia, TSK), 時間割引率(Time discounting, TD)を計測した。さらにfMRIにより安静時の脳信号を計測し, 両群を比較した。全脳解析では, 背外側前頭前野(DLPFC)と他のいくつかの関心領域(Region of Interest, ROI)との機能的結合性(Functional Connectivity, FC)が, 患者群と健常者群で有意に異なっていた。患者群におけるTSKスコアとDLPFC-島皮質間のFCの強さは有意な相関があった。また, 患者群におけるTDとDLPFC-側頭葉間のFCの強さも有意な相関があった。本研究により, 慢性痛患者では, 健常者と比較し, 有意にFCが異なる脳領域が存在し, その中には, 患者のもつ恐怖回避思考や衝動性と強く関連するFCがあることがわかった。将来的に, 安静時fMRIが慢性痛患者の心理行動のバイオマーカーとして利用でき, オーダーメイドの行動医学的介入により, 脳機能の改善を伴う新しい慢性痛治療の開発につながる可能性が示唆された。
Chronic pain poses a large socioeconomic burden including restrictions on social life and the cost of healthcare. Fear of pain can lead to the avoidance of activities (kinesiophobia), catastrophic thinking, and depression, resulting in intractable and prolonged pain. This vicious cycle, which is known as the fear avoidance model, has been used to explain how individuals develop chronic pain. In addition, to obtain pain relief, chronic pain patients tend to impulsively accept medical practices and folk remedies that are not necessarily appropriate. In this study, we focused on fear avoidance belief and impulsiveness among psycho-behavioral features of chronic pain, and examined the influence of these psychological behaviors on brain function using a resting-state functional magnetic resonance image (fMRI). After obtaining IRB approval and written informed consent, 20 subjects with chronic pain regularly attending Pain Clinic at Keio University Hospital and 20 age- and sex-matched healthy volunteers who did not suffer from pain were recruited. The degree of chronic pain, kinesiophobia (Tampa Scale for kinesiophobia, TSK), time discounting rate (TD) were assessed using questionnaire. The brain signals at rest were measured by resting state fMRI and were compared between the groups. In the whole brain analysis, the functional connectivity (FC) between the dorsolateral prefrontal cortex (DLPFC) and several other regions of interest (ROI) was significantly different between the patient group and healthy volunteer group. In the patient group, there was a significant correlation between the TSK scores and the intensity of FC between DLPFC and the insular cortex. In addition, the TD was significantly correlated with the intensity of FC between DLPFC and the temporal lobe. This study indicated that in chronic pain patients, several FCs between brain regions associated with emotion and pain were altered, and that some of these FCs were strongly associated with the patient's fear avoidance belief and impulsiveness. In the future, resting fMRI could be used as a biomarker of psychological behavior of chronic pain patients, suggesting the possibility that tailor-made behavioral intervention leads to development of new analgesic strategy accompanied with improvement of brain function in chronic pain.