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.

Physiopathological role of the enzymatic complex 5α-reductase and 3α/β-hydroxysteroid oxidoreductase in the generation of progesterone and testosterone neuroactive metabolites

“…In this case, the increase in the levels of THP and in the expression and activity of 3α-HSOR seem to be an adaptive response to control pain (Patte-Mensah et al, 2010;Patte-Mensah et al, 2014). In agreement with this interpretation, a decreased expression of 5α-R type 1 and type 2 in the dorsal spinal cord has been shown to be associated with the manifestation of allodynic behaviors in animals with spinal cord injury (Coronel et al, 2016). Furthermore, there is an increase in THP levels in the rat lateral thalamus (i.e., an important brain region for pain modulation) after spared nerve injury (Zhang et al, 2016).…”

TRP Channels as Potential Targets for Sex-Related Differences in Migraine Pain

“…Progesterone is the other steroid hormone that, together with estradiol, regulates the estral cycle in rodents and the menstrual cycle in humans. There are a plethora of studies linking progesterone to anti-nociception in neuropathic pain models (Coronel et al, 2011 , 2016 ; Verdi et al, 2013 ; Jarahi et al, 2014 ; Liu et al, 2014 ). In this context, the few studies that investigated the putative effects of progesterone in the expression and functional modulation of thermoTRPs showed mainly an inhibitory role of this hormone.…”

Deletion of RhoA in Progesterone Receptor–Expressing Cells Leads to Luteal Insufficiency and Infertility in Female Mice

“…P4 was shown to induce StAR expression in Leydig cell line MA-10 (40) and StAR mRNA expression in the injured spinal cord (41). Does P4 signaling regulate StAR expression in CL in vivo ?…”

“…P4 and progestin R5020, but not other steroids, induced StAR expression in Leydig cell line MA-10 (40). P4 treatment increased StAR mRNA expression in the injured spinal cord (41). However, another study indicated that P4 treatment decreased StAR mRNA expression in ex vivo fathead minnow ovary (66).…”