Progesterone regulates inflammasome expression after spinal cord injury: implications for neuropathic pain

M.F. CORONEL; M.C. RAGGIO; S.L. GONZALEZ

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Sociedad Argentina de Investigación Clínica

Abstract: Neuropathic pain, a frequent complication after spinal cord injury (SCI), is refractory to available treatment. Spinal glial cell activation and production of pro-inflammatory mediators, like IL-1β and IL-18, have a critical role in the development of this chronic pain. Neuroinflammatory processes triggered after SCI involve the activation of multiprotein complexes called inflammasomes, containing three main components: NLRP3, ASC and pro-caspase-1. Caspase-1 processes the precursors of IL-1β and IL-18 to its mature forms. We have shown that progesterone (PG), a neuroactive steroid, prevents pain and exerts anti-inflammatory actions. To analize whether these effects involve the modulation of NLRP3 inflammasome, we studied temporal changes in the expression of its components in the acute phase after SCI. Male rats were subjected to spinal hemisection at T13 level and received daily subcutaneous injections of PG (Hx+PG; 16 mg/kg, n=16) or vehicle (HX, n=16). Uninjured rats were used as control (C). Epicenter spinal cord segments were obtained 1 and 3 days post-injury and the mRNA levels of NLPR3, ASC, IL-1β, IL-18 and P2X7 purinergic receptor, involved in inflammasome activation, were determined using RT-PCR. Injured animals showed a significant raise in NLRP3 (p