title: Temporal changes in the expression of the translocator protein TSPO and the steroidogenic enzyme 5α-reductase in the dorsal spinal cord of animals with neuropathic pain: Effects of progesterone administration.
abstract: Neuropathic pain is a frequent complication of spinal cord injury (SCI), still refractory to conventional treatment. The presence and biological activity of steroidogenic regulatory proteins and enzymes in the spinal cord suggests that neurosteroids locally generated could modulate pain messages. In this study we explored temporal changes in the spinal expression of the 18kDa translocator protein TSPO, the steroidogenic acute regulatory protein (StAr) and the steroidogenic enzyme 5α-reductase (5α-RI/II) in an experimental model of central chronic pain. Male Sprague-Dawley rats were subjected to a SCI and sacrificed at different time points (1, 14 or 28days). The development of mechanical and cold allodynia was assessed. Injured animals showed an early increase in the mRNA levels of TSPO and 5α-RII, whereas in the chronic phase a significant decrease in the expression of 5α-RI and 5α-RII was observed, coinciding with the presence of allodynic behaviors. Furthermore, since we have shown that progesterone (PG) administration may offer a promising perspective in pain modulation, we also evaluated the expression of steroidogenic proteins and enzymes in injured animals receiving daily injections of the steroid. PG-treated did not develop allodynia and showed a marked increase in the mRNA levels of TSPO, StAR, 5α-RI and 5α-RII 28days after injury. Our results suggest that in the acute phase after SCI, the increased expression of TSPO and 5α-RII may represent a protective endogenous response against tissue injury, which is not maintained in the chronic allodynic phase. PG may favor local steroidogenesis and the production of its reduced metabolites, which could contribute to the antiallodynic effects observed after PG treatment.
authors.affiliation: Laboratorio de Nocicepción y Dolor Neuropático, Instituto de Biología y Medicina Experimental, CONICET, Vuelta de Obligado 2490, C1428ADN, Buenos Aires, Argentina.
authors.forename: María F
authors.initials: MF
authors.lastname: Coronel
authors.affiliation: Laboratorio de Nocicepción y Dolor Neuropático, Instituto de Biología y Medicina Experimental, CONICET, Vuelta de Obligado 2490, C1428ADN, Buenos Aires, Argentina.
authors.forename: María L
authors.initials: ML
authors.lastname: Sánchez Granel
authors.affiliation: Laboratorio de Nocicepción y Dolor Neuropático, Instituto de Biología y Medicina Experimental, CONICET, Vuelta de Obligado 2490, C1428ADN, Buenos Aires, Argentina.
authors.forename: María C
authors.initials: MC
authors.lastname: Raggio
authors.affiliation: Laboratorio de Nocicepción y Dolor Neuropático, Instituto de Biología y Medicina Experimental, CONICET, Vuelta de Obligado 2490, C1428ADN, Buenos Aires, Argentina.
authors.forename: Natalia S
authors.initials: NS
authors.lastname: Adler
authors.affiliation: Laboratorio de Bioquímica Neuroendócrina, Instituto de Biología y Medicina Experimental, CONICET, Vuelta de Obligado 2490, C1428ADN, Buenos Aires, Argentina; Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, C1121ABG, Buenos Aires, Argentina.
authors.forename: Alejandro F
authors.initials: AF
authors.lastname: De Nicola
authors.affiliation: Laboratorio de Bioquímica Neuroendócrina, Instituto de Biología y Medicina Experimental, CONICET, Vuelta de Obligado 2490, C1428ADN, Buenos Aires, Argentina; Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, C1121ABG, Buenos Aires, Argentina.
authors.forename: Florencia
authors.initials: F
authors.lastname: Labombarda
authors.affiliation: Laboratorio de Nocicepción y Dolor Neuropático, Instituto de Biología y Medicina Experimental, CONICET, Vuelta de Obligado 2490, C1428ADN, Buenos Aires, Argentina; Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155, C1121ABG, Buenos Aires, Argentina. Electronic address: sugnzlz@gmail.com.
authors.forename: Susana L
authors.initials: SL
authors.lastname: González
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D042944:Cholestenone 5 alpha-Reductase / Q000378:metabolism*; D006930:Hyperalgesia / Q000201:enzymology / Q000209:etiology / Q000378:metabolism; D008297:Male; D009437:Neuralgia / Q000201:enzymology / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D017288:Pain Threshold / Q000187:drug effects; D011374:Progesterone / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000150:complications / Q000201:enzymology / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D012333:RNA, Messenger; D011963:Receptors, GABA-A; C069997:Tspo protein, rat; D011374:Progesterone; D042944:Cholestenone 5 alpha-Reductase
keywords: 18kDa translocator protein TSPO; 5α-Reductase; Chronic pain; Progesterone; Spinal cord injury; Steroidogenesis