Abstract |
Pain is an unpleasant perception often caused by intense or damaging stimuli.
Many types of pain have been described according to its different components, such
as duration, location, and type of system that influences. In this study, we focused on
inflammatory pain that occurs after tissue injury or infection, and is interwoven with
immune system response. This situation causes discomfortness, stress and fear to the
individual, but pain is also protective by preventing the individual to further use the
injured member.
Neurosteroids, like DHEA and Allopregnanolone have been demonstrated to
exert positive effects in pain and hyperalgesia, as has been shown in pain models like
caraggeenan-induced inflammation. A new synthetic analogue of DHEA has been
recently developed, which conserves the immunomodulatory effects of DHEA, but
lacks the endocrine properties of it (BNN27). Thus, the aim of our study was to
examine the effect of BNN27 on inflammatory pain using the mouse model of
inflammation and hyperalgesia induced by Complete’s Freund’s Adjuvant (CFA) in
hind paw.
Specifically, we focused on the contribution of BNN27 in basal and
inflammatory pain, and edema and the mechanism BNN27 likely mediates its effects,
through. Our results demonstrated that BNN27 has positive effect on basal and
inflammatory pain, as it increased pain thresholds in treated mice, but it did not
influence edema. BNN27 increased protein levels of TNF-a, IL-6, and NGF at 6 hours
following the induction of inflammation, while it decreased TNF-aat 24 hours
following inflammation. IL-6 and NGF were unchanged at 24 hours, while IL-10 was
elevated in BNN27-treated mice at all time points examined. In DRGs, NGF was
decreased at 6 and 24 hours after CFA injection. The analgesic affect of BNN27
seems to be mediated by μ-opioid receptor (MOR), as its mRNA expression levels
were elevated in inflamed tissue and DRGs. M-opioid receptor ligand, β-endorphin
and its precursor POMC were also elevated at 6 hours, while the mRNA of PENK, the
precursor of enkephalins, was elevated at 24 hours.
Our data indicate a potential role of BNN27 on inflammatory pain. Most
studies with this compound so far were focused on its beneficial effect in
neuroprotection. Here we show its positive contribution in another system, that of
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pain and inflammation. Further studies are in progress to clarify its role and the
mechanism in these conditions.
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