title: Poly(ADP-ribose) polymerase inhibition reveals a potential mechanism to promote neuroprotection and treat neuropathic pain.
abstract: Neuropathic pain is triggered by the lesions to peripheral nerves which alter their structure and function. Neuroprotective approaches that limit the pathological changes and improve the behavioral outcome have been well explained in different experimental models of neuropathy but translation of such strategies to clinics has been disappointing. Experimental evidences revealed the role of free radicals, especially peroxynitrite after the nerve injury. They provoke oxidative DNA damage and consequent over-activation of the poly(ADP-ribose) polymerase (PARP) upregulates pro-inflammatory pathways, causing bioenergetic crisis and neuronal death. Along with these changes, it causes mitochondrial dysfunction leading to neuronal apoptosis. In related preclinical studies agents that neutralize the free radicals and pharmacological inhibitors of PARP have shown benefits in treating experimental neuropathy. This article reviews the involvement of PARP over-activation in trauma induced neuropathy and therapeutic significance of PARP inhibitors in the experimental neuropathy and neuropathic pain.
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Hyderabad, Balanagar, India.
authors.forename: Prashanth
authors.initials: P
authors.lastname: Komirishetty
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Hyderabad, Balanagar, India.
authors.forename: Aparna
authors.initials: A
authors.lastname: Areti
authors.affiliation: Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Assam, India.
authors.forename: Ranadeep
authors.initials: R
authors.lastname: Gogoi
authors.affiliation: Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad, India.
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Sistla
authors.affiliation: Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Hyderabad, Balanagar, India.
authors.forename: Ashutosh
authors.identifier: 0000-0001-6659-4751
authors.initials: A
authors.lastname: Kumar
keywords: bioenergetic crisis; neuroinflammation; neuropathic pain; oxidative stress; poly(ADP-ribose) polymerase