Hemokinin-1(4-11)-Induced Analgesia Selectively Up-Regulates δ-Opioid Receptor Expression in Mice

Abstract

Our previous studies have shown that an active fragment of human tachykinins (hHK-1(4-11)) produced an opioid-independent analgesia after intracerebroventricular (i.c.v.) injection in mice, which has been markedly enhanced by a δ OR antagonist, naltrindole hydrochloride (NTI). In this study, we have further characterized the in vivo analgesia after i.c.v. injection of hHK-1(4-11) in mouse model. Our qRT-PCR results showed that the mRNA levels of several ligands and receptors (e.g. PPT-A, PPT-C, KOR, PDYN and PENK) have not changed significantly. Furthermore, neither transcription nor expression of NK1 receptor, MOR and POMC have changed noticeably. In contrast, both mRNA and protein levels of DOR have been up-regulated significantly, indicating that the enhanced expression of δ opioid receptor negatively modulates the analgesia induced by i.c.v. injection of hHK-1(4-11). Additionally, the combinatorial data from our previous and present experiments strongly suggest that the discriminable distribution sites in the central nervous system between hHK-1(4-11) and r/mHK-1 may be attributed to their discriminable analgesic effects. Altogether, our findings will not only contribute to the understanding of the complicated mechanisms regarding the nociceptive modulation of hemokinin-1 as well as its active fragments at supraspinal level, but may also lead to novel pharmacological interventions.

Analgesic effects of lappaconitine in leukemia bone pain in a mouse model

“…The total RNA was extracted from the tibial bone marrow cells using TRlzol Reagent (Invitrogen Corp., Carlsbad, California, USA) according to the manufacturer’s instructions. Two µg of total RNA in each group was reverse transcribed into cDNA in a final volume of 50 µl as in previous reports ( Fu et al, 2014 ; Zhang et al, 2014 ). The gene of GAPDH was selected as an endogemous internal control gene and a non-template reaction was included as negative control for each experiment.…”

Hemokinin-1 Gene Expression Is Upregulated in Trigeminal Ganglia in an Inflammatory Orofacial Pain Model: Potential Role in Peripheral Sensitization

“…HK-1 had a pronociceptive effect after intrathecal or intracerebroventricular administration, causing pain and scratching behavior without influencing the withdrawal latency to a noxious heat stimulus [34,43]. However, in other studies, an analgesic effect was shown upon intracerebroventricular injection [44][45][46]. Its potential contribution to pain sensitization was shown by the upregulation of Tac4 mRNA expression in lipopolysaccharide-stimulated cultured microglia [47], and in the rat spinal dorsal horn after complete Freund's adjuvant (CFA)-induced paw inflammation [48].…”

Nanoscale TiO2 nanotubes govern the biological behavior of human glioma and osteosarcoma cells

“…Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis were then performed as described previously, with minor modifications. 32 A total of 50 μg of protein from each sample was resolved by sodium dodecyl sulfate polyacrylamide gel electrophoresis, transferred onto polyvinylidene fluoride membranes (Roche, Indianapolis, IN, USA) by electroblotting, and probed with specific primary antibodies, including monoclonal mouse anti-p-FAK (1:1,000, Santa Cruz Biotechnology, Santa Cruz, CA, USA), monoclonal mouse anti-human vitronectin (1:1,000, R&D Systems), monoclonal mouse anti-human Bcl-2 (1:500, Santa Cruz Biotechnology), monoclonal mouse anti-human Bax (1:500, Santa Cruz Biotechnology, and monoclonal mouse anti-human caspase-3 (1:1,000, R&D Systems). The primary antibodies were detected using horseradish peroxidase-conjugated goat anti-mouse IgG (1:5,000, Promega, Heidelberg, Germany) in blocking solution.…”