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.

Background: Cisplatin (CP), a platinum-based chemotherapeutic agent, is widely used to treat cancer but causes nephrotoxicity. Riociguat, a soluble guanylate cyclase (sGC) stimulator that enhances the nitric oxide–sGC–cGMP signaling pathway, was investigated for its potential protective effects against cisplatin-induced nephrotoxicity. Materials and Methods: Rats were randomly divided into four equal groups (six rats each) and treated for nine consecutive days. The first and second groups were given oral carboxymethylcellulose 0.5% (vehicle) for 9 days, and on day 6 were injected intraperitoneally with saline or CP, respectively. The third and fourth groups were treated orally with two doses of riociguat (3 and 10 mg/kg/day) for 9 days, and received intraperitoneal injections of CP on day 6. Blood, urine, and kidney tissues were analyzed 24 h after the last treatment. Results: CP significantly elevated the markers of kidney function, including uric acid, serum creatinine, and urea. CP also caused histological kidney damage. Antioxidant markers, including catalase (CAT), glutathione reductase (GR), superoxide dismutase (SOD), and total antioxidant capacity (TAC) were significantly reduced, while inflammatory cytokines (IL-1β, IL-6, and TNF-α) and lipid peroxidation (MDA) were markedly increased. Riociguat improved kidney structure and significantly reduced kidney function markers, MDA, and inflammatory cytokines while restoring GR, TAC, SOD, and CAT activities. Conclusions: These results indicate that riociguat exerts protection of the kidneys from CP-caused kidney damage by antioxidation and anti-inflammation. Riociguat may have potential as an adjunct therapy to mitigate CP-associated nephrotoxicity.

Chitosan-pimelate (CS-Pim) mucoadhesive buccal films were developed to improve the therapeutic efficacy of duloxetine (DLX) using sage oil-based lipid carriers (DLX-SLCs). This buccal nanoplatform addresses DLX’s limited oral bioavailability and extensive first-pass metabolism by providing a non-invasive route with enhanced mucosal permeability and sustained release. DLX-SLCs were optimized and characterized for particle size, zeta potential, and entrapment efficiency. The carriers incorporated into CS-Pim buccal films, which were evaluated for physicochemical properties, morphology, hydrophilicity, and mucoadhesive strength. In vivo antidepressant efficacy was assessed in a lipopolysaccharide (LPS)-induced rat depression model using behavioral tests, biochemical markers, and histopathological analysis. Optimized DLX-SLCs yielded an average size of 130.9±2.4 nm, zeta potential of −28.4 ±2.3 mV, and entrapment efficiency of 79.9 ± 3.8%. The selected film exhibited desirable physicochemical attributes, including uniform thickness, pH (7.08 ± 0.03), drug content (99.1 ± 0.4%), tensile strength (10.07 ± 0.34 N/cm²), elongation at break (109.9 ± 7.3%), swelling index (124%), mucoadhesive strength (48.9 ± 2.38 g), and smooth surface via SEM. FTIR and DSC confirmed successful polymer modification, drug encapsulation, and amorphous dispersion of DLX within the matrix. Contact angle analysis confirmed improved hydrophilicity. DLX-SLCs buccal films exhibited superior curative efficacy compared to pure-DLX and the marketed-DLX in lipopolysaccharide (LPS)-induced rat depression model. Behavioral assessments demonstrated a 60% reduction in immobility time, an increase in open-arm entries, and sucrose preference by a 3.29-fold and 2-fold, respectively, compared to the LPS group. Biochemical analyses revealed reduced TNF-α, IL-1β, and cortisol levels by 67.6%, 64.4%, and 53%, respectively. Alongside increased serotonin and GABA levels by 1.64-fold and 3.5-fold, respectively. Histopathological findings confirmed significant neuroprotective effects. DLX-SLCs incorporated into CS-Pim buccal films provide enhanced antidepressant efficacy and neuroprotective benefits, representing a bioadhesive and patient-compliant alternative to conventional DLX formulations for depression treatment.