Role of Sensory Pathway Injury in Central Post-Stroke Pain: A Narrative Review of Its Pathogenetic Mechanism

Abstract

Central post-stroke pain (CPSP) is a severe chronic neuropathic pain syndrome that is a direct result of cerebrovascular lesions affecting the central somatosensory system. The pathogenesis of this condition remains unclear owing to its extensive clinical manifestations. Nevertheless, clinical and animal experiments have allowed a comprehensive understanding of the mechanisms underlying CPSP occurrence, based on which different theoretical hypotheses have been proposed. We reviewed and collected the literature and on the mechanisms of CPSP by searching the English literature in PubMed and EMBASE databases for the period 2002–2022. Recent studies have reported that CPSP occurrence is mainly due to post-stroke nerve injury and microglial activation, with an inflammatory response leading to central sensitization and de-inhibition. In addition to the primary injury at the stroke site, peripheral nerves, spinal cord, and brain regions outside the stroke site are involved in the occurrence and development of CPSP. In the present study, we reviewed the mechanism of action of CPSP from both clinical studies and basic research based on its sensory pathway. Through this review, we hope to increase the understanding of the mechanism of CPSP.

Stroke-Induced Central Pain: Overview of the Mechanisms, Management, and Emerging Targets of Central Post-Stroke Pain

“…TNF- α formation in thalamic microglia mediated through NF-KB as well as ERK1/2 signaling is prompted with an increased expression of a non-receptor tyrosine kinase, Fgr belonging to the Src family following hemorrhage at the thalamus, thus inducing long-lasting hypersensitivity of pain responses including hyperalgesia (heat and cold) and mechanical allodynia contralaterally [ 41 ]. Microglial activation and proliferation are reported to be mediated via purinergic receptor (P2X) signaling, SDF1–CXCR4, and Fgr through NF-KB–ERK1/2 signaling and thereby contributing to the development of CPSP [ 42 ].…”

Successful pain control with add-on methadone for refractory neuropathic pain due to radiation necrosis in pontine metastatic lesion: A case report

“…Central pain commonly manifests as neuropathic pain within six months following an injury [1], and its underlying causes range from strokes to traumatic brain injuries [3]. The pain can be characterized by sensations such as pricking, aching, lancinating, tearing, shooting, and squeezing, often accompanied by dysaesthesia, hyperalgesia, and allodynia [2].…”

“…Central pain, often referred to as thalamic pain or central post-stroke pain (CPSP), arises from disruptions in the ascending sensory pathway, particularly involving the thalamus [1]. However, it is crucial to note that any injury to the superior spinothalamic tract, including within the brainstem, can result in the development of central pain [2]. Central pain commonly manifests as neuropathic pain within six months following an injury [1], and its underlying causes range from strokes to traumatic brain injuries [3].…”