Brain Stimulation Therapy for Central Post-Stroke Pain from a Perspective of Interhemispheric Neural Network Remodeling

Abstract

Central post-stroke pain (CPSP) is a debilitating, severe disorder affecting patient quality of life. Since CPSP is refractory to medication, various treatment modalities have been tried with marginal results. Following the first report of epidural motor cortex (M1) stimulation (MCS) for CPSP, many researchers have investigated the mechanisms of electrical stimulation of the M1. CPSP is currently considered to be a maladapted network reorganization problem following stroke, and recent studies have revealed that the activities of the impaired hemisphere after stroke may be inhibited by the contralesional hemisphere. Even though this interhemispheric inhibition (IHI) theory was originally proposed to explain the motor recovery process in stroke patients, we considered that IHI may also contribute to the CPSP mechanism. Based on the IHI theory and the fact that electrical stimulation of the M1 suppresses CPSP, we hypothesized that the inhibitory signals from the contralesional hemisphere may suppress the activities of the M1 in the ipsilesional hemisphere, and therefore pain suppression mechanisms may be malfunctioning in CPSP patients. In this context, transcranial direct current stimulation (tDCS) was considered to be a reasonable procedure to address the interhemispheric imbalance, as the bilateral M1 can be simultaneously stimulated using an anode (excitatory) and cathode (inhibitory). In this article, we review the potential mechanisms and propose a new model of CPSP. We also report two cases where CPSP was addressed with tDCS, discuss the potential roles of tDCS in the treatment of CPSP, and make recommendations for future studies.

Microglial depletion under thalamic hemorrhage ameliorates mechanical allodynia and suppresses aberrant axonal sprouting

“…Although the underlying mechanism of CPSP remains largely unknown, maladaptive network reorganization is considered a key feature (4,5). Based on clinical and experimental observations, various abnormal network models have been proposed to explain the development of CPSP, and many of them emphasize the importance of hyperactivity of the thalamocortical circuit (1,5). However, neuroanatomical evidence of neural circuit reorganization is lacking.…”

Study of cortical motor representation and cortical excitability in refractory neuropathic pain

“…慢性神経障害性疼痛は，本邦で 100 万人以上 の有病率と推測され，患者の日常生活動作を阻 害し，医療費など社会保障費の増大だけでなく 就 労 困 難 を 招 く な ど 社 会 的 損 失 も 多 大 で あ る 10) 。難治性疼痛に対する治療法として，一次 運動野電気刺激術や 23) ，非侵襲的脳刺激法に代 表される反復経頭蓋磁気刺激療法(repetitive transcranial magnetic stimulation; rTMS)によ る一次運動野刺激の除痛効果が報告されている ことから 6,17) ，一次運動野(M1)が疼痛の認知 に関与している可能性が考えられる。難治性疼 痛の発現機序として，脳機能画像の研究から疼 痛認知や情動に関与する脳内領域(疼痛ネット ワーク)だけでなく，M1 領域周囲の変化も報 告されており 9,12) ，運動系を加えた脳内ネット ワークの不適切な機能再構築(maladaptation) が想定されている 8,13,15) 。さらに，M1 を含む大 脳皮質機能領域は，脳卒中後の運動機能の回復 過程において，大脳皮質機能が再構築(cortical reorganization)されることが示されている 11,18) Although RMT of AH trended to be higher than that of UH, there was no significant difference in RMT. RMT, resting motor threshold; MSO, maximum stimulu s output; AH, affected hemisphere; UH, unaffected hemisphere.…”

Deep Brain Stimulation for the Treatment of Dejerine-Roussy Syndrome

“…This “disinhibition theory” is characterized by imbalances, such as an abnormal transmission of thermal or touch stimuli, leading to inappropriate responses such as touch sensitivity or burning pain [16,17]. Additionally, thalamic hyperactivity on the contralesional hemisphere and ipsilateral anterior cingulate cortex (ACC) hypoactivity have been observed in patients experiencing allodynia [18].…”

“…Larger neuronal losses after an infarct, in combination with proliferation of glia or microglia in the perilesional area, can lead to more severe allodynia [20]. More recent work has shifted the view on DRS into the context of a network remodeling disorder, suggesting that chronic pain states involve mechanisms different from those of typical spontaneous pain [17,18,21]. Supporting this viewpoint, complete infarction of the somatosensory cortex can lead to compensatory contralateral hemispheric reorganization [17,22].…”

“…More recent work has shifted the view on DRS into the context of a network remodeling disorder, suggesting that chronic pain states involve mechanisms different from those of typical spontaneous pain [17,18,21]. Supporting this viewpoint, complete infarction of the somatosensory cortex can lead to compensatory contralateral hemispheric reorganization [17,22]. A recent study showed that the inhibitory mechanism of the thalamocortical GABA system was reversed in a rodent model of the disorder, leading to enhanced spontaneous activity and noxious responses of the thalamus secondary to the development of DRS [1,20].…”