The incidence of stroke plays the foremost role in the genesis of central neuropathic pain. Central post-stroke pain (CPSP) is a central pain arising from a vascular lesion in the central nervous system that elicits somatosensory deficits, often contralateral to stroke lesions. It is expressed as continuous or intermittent pain accompanied by sensory abnormalities like dysesthesia and allodynia. CPSP remains de-emphasized due to the variation in onset and diversity in symptoms, besides the difficulty of distinguishing it from other post-stroke pains, often referred to as a diagnosis of exclusion. Spinothalamic dysfunction, disinhibition of the medial thalamus, and neuronal hyperexcitability combined with deafferentation in thalamocortical regions are the mechanisms underlying central pain, which play a significant role in the pathogenesis of CPSP. The treatment regimen for CPSP seems to be perplexed in nature; however, based on available studies, amitriptyline and lamotrigine are denoted as first-line medications and non-pharmacological choices may be accounted for cases intractable to pharmacotherapy. This review attempts to provide an overview of the mechanisms, existing management approaches, and emerging targets of CPSP. A profound understanding of CPSP aids in optimizing the quality of life among stroke sufferers and facilitates further research to develop newer therapeutic agents for managing CPSP.

Bruton’s tyrosine kinase (BTK) is a critical component in B-cell receptor (BCR) signaling and is also expressed in haematogenic and innate immune cells. Inhibition of BTK hyperactivity is implicated in B-cell malignancies and autoimmune diseases. This review derives the structural complementarity of the BTK-kinase domain and its inhibitors from recent three-dimensional structures of inhibitor-bound BTK in the protein data bank (PDB). Additionally, this review analyzes BTK-mediated effector responses of B-cell development and antibody production. Covalent inhibitors contain an α, β-unsaturated carbonyl moiety that forms a covalent bond with Cys481, stabilizing αC-helix in inactive-out conformation which inhibits Tyr551 autophosphorylation. Asn484, located two carbons far from Cys481, influences the stability of the BTK-transition complex. Non-covalent inhibitors engage the BTK-kinase domain through an induced-fit mechanism independent of Cys481 interaction and bind to Tyr551 in the activation kink resulting in H3 cleft, determining BTK selectivity. Covalent and non-covalent binding to the kinase domain of BTK shall induce conformational changes in other domains; therefore, investigating the whole-length BTK conformation is necessary to comprehend BTK’s autophosphorylation inhibition. Knowledge about the structural complementarity of BTK and its inhibitors supports the optimization of existing drugs and the discovery of drugs for implication in B-cell malignancies and autoimmune diseases.