Attenuating effect of Cilostazol against vincristine – Induced neuropathic pain in mice

Mohanan, Anugeetha Thacheril; Suba, V.; Sermugapandian, Nithya; Al-Safhi, Mohammed; Khan, Gyas

doi:10.1016/j.jopr.2013.04.041

Cited by 1 publication

(1 citation statement)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the current investigation, CLZ deactivation of the NLRP3 inflammasome is the underpins of the contracted central neuropathic pain perception verified herein by a series of behavioral tests assessing both mechanical and cold allodynia, as well as hyperalgesia using the Randal Sellito analgesy-meter consequent to cerebral transient ischemic insult. Notably, Thacheril et al [ 46 ] reported that the drug ameliorated mechanical hyperalgesia/allodynia provoked by vincristine in mice. However, to the authors’ knowledge, this is the first report documenting the capacity of CLZ post-treatment to effectively abrogate the crucial NLRP3 inflammasome mechanistic pathway triggered by glutamatergic transmission associated with central pain sensation.…”

Section: Discussionmentioning

confidence: 99%

Cilostazol Alleviates NLRP3 Inflammasome–Induced Allodynia/Hyperalgesia in Murine Cerebral Cortex Following Transient Ischemia: Focus on TRPA1/Glutamate and Akt/Dopamine/BDNF/Nrf2 Trajectories

et al. 2022

View full text Add to dashboard Cite

Global cerebral ischemia/reperfusion (I/R) provokes inflammation that augments neuropathic pain. Cilostazol (CLZ) has pleiotropic effects including neuroprotection in several ravaging central disorders; nonetheless, its potential role in transient central ischemic-induced allodynia and hyperalgesia has not been asserted before. Rats were allocated into 4 groups; sham, sham + CLZ, and 45 min-bilateral carotid occlusion followed by a 48 h-reperfusion period either with or without CLZ (50 mg/kg; p.o) post-treatment. CLZ prolonged latency of hindlimb withdrawal following von Frey filaments, 4 °C cold, and noxious mechanical stimulations. Histopathological alterations and the immunoexpression of glial fibrillary acidic protein induced by I/R were reduced by CLZ in the anterior cingulate cortex (ACC) area, while, CLZ enhanced intact neuronal count. Meanwhile, CLZ modulated cerebral cortical glutamate, dopamine neurotransmission, and transient receptor potential ankyrin 1 (TRPA1). CLZ anti-inflammatory potential was mediated by the downregulated p65 NF-κB and sirtuin-1 enhancement to reduce nucleotide-binding domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), active caspase-1, and interleukin-1β, indicative of inflammasome deactivation. It also revealed an antioxidant capacity via boosting nuclear factor E2-related factor (Nrf2) enhancing glutathione through forkhead box protein O3a (FOXO3a) reduction. Additionally, CLZ triggered neuronal survival by promoting the p-content of Akt, TrkB, and CREB as well as BDNF content. A novel approach of CLZ in hindering global cerebral I/R–mediated neuropathy is firstly documented herein to forward its adjunct action via deactivating the NLRP3 inflammasome, besides enhancing Nrf2 axis, neuronal survival, and dopamine neurotransmission as well as inhibiting TRPA1 and excitotoxicity. Graphical abstract

show abstract

Section: Discussionmentioning

confidence: 99%