Cell cycle inhibition limits development and maintenance of neuropathic pain following spinal cord injury. Issue 2 (February 2016)

• Record Type: Journal Article
• Authors: Wu, Junfang; Zhao, Zaorui; Zhu, Xiya; Renn, Cynthia L.; Dorsey, Susan G.; Faden, Alan I.
• Is Part Of: Pain. Volume 157:Issue 2(2016)
• Publication Date: 2016-02
• Subjects: Spinal cord injury -- Neuropathic pain -- Spontaneous pain -- Cell cycle inhibition -- Inflammation; Pain -- Periodicals; Douleur -- Périodiques; Anesthésie -- Périodiques; Pain; Electronic journals; Periodicals; Electronic journals; 616.0472
• DOI: 10.1097/j.pain.0000000000000393
• Languages: English
• ISSNs: 0304-3959

Abstract

Abstract : Abstract: Chronic pain after spinal cord injury (SCI) may present as hyperalgesia, allodynia, and/or spontaneous pain and is often resistant to conventional pain medications. Identifying more effective interventions to manage SCI pain requires improved understanding of the pathophysiological mechanisms involved. Cell cycle activation (CCA) has been implicated as a key pathophysiological event following SCI. We have shown that early central or systemic administration of a cell cycle inhibitor reduces CCA, prevents glial changes, and limits SCI-induced hyperesthesia. Here, we compared the effects of early vs late treatment with the pan-cyclin–dependent kinase inhibitor flavopiridol on allodynia as well as spontaneous pain. Adult C57BL/6 male mice subjected to moderate SCI were treated with intraperitoneal injections of flavopiridol (1 mg/kg), daily for 7 days beginning either 3 hours or 5 weeks after injury. Mechanical/thermal allodynia was evaluated, as well as spontaneous pain using the mouse grimace scale (MGS). We show that sensitivity to mechanical and thermal stimulation, and locomotor dysfunction were significantly reduced by early flavopiridol treatment compared with vehicle-treated controls. Spinal cord injury caused robust and extended increases of MGS up to 3 weeks after trauma. Early administration of flavopiridol significantly shortened duration of MGS changes. Late flavopiridol intervention significantly limited hyperesthesia at 7 days after treatment, associated with reduced glial changes, but without effect on locomotion. Thus, our data suggest that cell cycle modulation may provide an effective therapeutic strategy to reduce hyperesthesia after SCI, with a prolonged therapeutic window. Abstract : Spinal cord injury causes spontaneous pain and hyperesthesia. Cell cycle inhibition limits such changes, possibly by limiting microglial/astrocyte activation.