Takahashi Miwako, Kasahara Satoshi, Soma Tsutomu, Morita Taito, Sato Naoko, Matsudaira Ko, Niwa Shin-Ichi, Momose Toshimitsu
Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology, Chiba, Japan.
Department of Anesthesiology and Pain Relief Center, The University of Tokyo Hospital, Tokyo, Japan.
Front Pharmacol. 2024 Oct 17;15:1480546. doi: 10.3389/fphar.2024.1480546. eCollection 2024.
Nociplastic pain (NP), a third category of chronic pain, offers a framework for elucidating its pathophysiology and treatment strategies. One of the characteristics of NP is comorbidity of symptoms other than pain, such as psychological and cognitive problems; therefore, these can be clues to understanding NP. Recently, we reported several cases with comorbid symptoms of attention-deficit/hyperactivity disorder (ADHD). Notably, ADHD medications, including methylphenidate (MP) and atomoxetine, improved chronic pain as well as the symptoms of ADHD. However, in clinical settings, identifying comorbid ADHD in patients with chronic pain is challenging, and underlying mechanisms have not been elucidated. To explore the common characteristics of brain function in patients with ADHD-comorbid NP, we identified brain regions where cerebral blood flow (CBF) distributions changed between pre- and post-treatment using single-photon emission computed tomography (SPECT). Additionally, we examined brain regions where CBF values correlated with clinical scores.
We retrospectively studied 65 patients (mean age 53 ± 14 years; 30 males and 35 females) with ADHD-comorbid NP who underwent CBF-SPECT before and after ADHD medication initiation. Clinical scores included the clinical global impression severity (CGI-S), pain numerical rating scale, hospital anxiety and depression scale, pain catastrophizing scale, and Conners' adult ADHD rating scale-self report scores. Voxel-based statistical methods were used to compare pre- and post-treatment CBF-SPECT images to identify significant differences and investigate brain regions correlated with clinical scores.
The CBF was higher in the precuneus, insular gyrus, and thalamus before treatment than after treatment (paired t-test, cluster-definition p < 0.001, cluster-extent threshold p < 0.05, with family-wise error [FWE] correction). The hyperperfusion in the precuneus was positively correlated with the CGI-S score and significantly reduced after treatment with MP (paired t-test, cluster-definition p < 0.005, cluster-extent threshold p < 0.05, with FWE correction).
The finding of precuneal hyperperfusion may provide insight into the mechanisms of NP and help identify patients who would benefit most from ADHD medications.
伤害感受性疼痛（NP）作为慢性疼痛的第三种类别，为阐明其病理生理学和治疗策略提供了一个框架。NP的特征之一是除疼痛外还伴有其他症状，如心理和认知问题；因此，这些症状可能是理解NP的线索。最近，我们报告了几例伴有注意力缺陷多动障碍（ADHD）合并症状的病例。值得注意的是，包括哌甲酯（MP）和托莫西汀在内的ADHD药物改善了慢性疼痛以及ADHD症状。然而，在临床环境中，识别慢性疼痛患者合并的ADHD具有挑战性，其潜在机制尚未阐明。为了探索合并ADHD的NP患者脑功能的共同特征，我们使用单光子发射计算机断层扫描（SPECT）确定了治疗前后脑血流（CBF）分布发生变化的脑区。此外，我们还检查了CBF值与临床评分相关的脑区。
我们回顾性研究了65例合并ADHD的NP患者（平均年龄53±14岁；男性30例，女性35例），这些患者在开始使用ADHD药物治疗前后均接受了CBF-SPECT检查。临床评分包括临床总体印象严重程度（CGI-S）、疼痛数字评定量表、医院焦虑抑郁量表、疼痛灾难化量表和康纳斯成人ADHD评定量表自我报告分数。基于体素的统计方法用于比较治疗前后的CBF-SPECT图像，以确定显著差异并研究与临床评分相关的脑区。
治疗前楔前叶、岛叶和丘脑的CBF高于治疗后（配对t检验，聚类定义p<0.001，聚类范围阈值p<0.05，采用家族性错误率[FWE]校正）。楔前叶的血流灌注过高与CGI-S评分呈正相关，MP治疗后显著降低（配对t检验，聚类定义p<0.005，聚类范围阈值p<0.05，采用FWE校正）。
楔前叶血流灌注过高的发现可能有助于深入了解NP的机制，并有助于确定最能从ADHD药物中获益的患者。
