Neuropeptides
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Orexinergic system may play an important role in the regulation of anesthesia-arousal. However, which region or which pathway mediated the effect of orexins was still unclear. In current study, we investigated whether activation of orexin signals in basal forebrain (BF) may alter electroencephalographic activity, induction and emergence time to sevoflurane anesthesia in rats. ⋯ Comparing with orexin-B, injection of lower dose of orexin-A induced more arousal EEG. Intrabasalis microinjection of orexin-A shorted the emergence time, whereas intrabasalis microinjection of SB-334867A (5 microg, 20 microg) delayed the emergence time to sevoflurane anesthesia, without changing anesthetic induction. These findings indicate that the orexin signals in basal forebrain, a middle region of the cholinergic ventral ascending arousal system, plays a crucial role in the anesthesia-arousal regulation.
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Endothelins, acting through specific endothelin ET(A) and/or ET(B) receptors, participate in nociceptive processing in models of cancer, inflammatory and neuropathic pain. The present study investigated which cell types express endothelin receptors in the trigeminal ganglion, and the contribution of mechanisms mediated by endothelin ET(A) and ET(B) receptors to orofacial heat hyperalgesia induced by unilateral constriction of the infraorbital nerve (CION). Both receptor types were identified by immunohistochemistry in the trigeminal ganglion, ET(A) receptors on small-sized non-myelinated and myelinated A-fibers and ET(B) receptors on both satellite glial cells and small-sized non-myelinated neuronal cells. ⋯ On the other hand, CION-induced heat hyperalgesia was transiently abolished over the first 90 min following i.p. injection of morphine hydrochloride (2.5 mg/kg), but fully resistant to reversal by indomethacin (4 mg/kg, i.p.) or celecoxib (10 mg/kg, i.p.). Thus, heat hyperalgesia induced by CION is maintained, in part, by peripheral signaling mechanisms operated by ET(A) and ET(B) receptors. Endothelin receptors might represent promising therapeutic targets for the control of trigeminal neuropathic pain.
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Single ligature nerve constriction (SLNC) of the rat sciatic nerve triggers neuropathic pain-related behaviors and induces changes in neuropeptide expression in primary afferent neurons. Bone marrow stromal cells (MSCs) injected into the lumbar 4 (L4) dorsal root ganglia (DRGs) of animals subjected to a sciatic nerve SLNC selectively migrate to the other ipsilateral lumbar DRGs (L3, L5 and L6) and prevent mechanical and thermal allodynia. In this study, we have evaluated the effect of MSC administration on the expression of the neuropeptides galanin and NPY, as well as the NPY Y(1)-receptor (Y(1)R) in DRG neurons. ⋯ In contrast, MSC administration partially prevented the injury-induced changes in galanin, NPY and Y(1)R expression. The large number of Y(1)R-immunoreactive neurons together with high levels of NPY expression in animals injected with MSCs could explain, at least in part, the analgesic effects exerted by these cells. Our results support MSC participation in the modulation of neuropathic pain and give insight into one of the possible mechanisms involved.
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Arginine-vasopressin (AVP) is synthesized and released centrally in several brain structures. AVP is thought to mediate anxiety-related behavior through two central receptor subtypes, Avpr1a and Avpr1b. Although these AVP receptor subtypes are expressed in several brain regions, including the hippocampus, little is known about their explicit role in unconditioned fear or anxiety. ⋯ Neither antagonist reduced anxiety-like behavior in the shock-probe burying test. Overall, the results show that both receptor subtypes of AVP are involved in anxiety-related responses, but their specific contributions depend on three variables: (1) the anxiety-related response (shock-probe avoidance versus open-arm avoidance), (2) the receptor subtype antagonized (Avpr1a versus Avpr1b), and (3) the area of hippocampus (dorsal versus ventral) into which these antagonists are infused. These dissociations suggest that different fear responses are under the control of specific AVP receptor systems within discrete parts of the hippocampus.
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[(3)H]Tyr-Tic-(2S,3R)-beta-MePhe-Phe-OH (where Tic: 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) with a specific radioactivity of 53.7 Ci/mmol was synthesized and characterized in receptor binding assays at 25 degrees C in rat brain membranes. The specific binding was saturable and displayed high affinity, with a K(D) of 0.16+/-0.005 nM and B(max) of 85.9+/-6.3 fmol/mg protein. NaCl increased its affinity by about 4-fold in membranes of rat brain and Chinese Hamster Ovary Cells stably transfected with the human delta-opioid receptors (hDOR-CHO) showing that the new ligand is an antagonist. ⋯ The unlabeled new ligand was about 7-fold more potent than the parent peptide in competing for the binding sites of [(3)H]Tyr-Tic-(2S,3R)-beta-MePhe-Phe-OH in rat brain membranes. Likewise, the threo-beta-methyl analog was 3.8-fold more potent than the parent compound in antagonizing the effect of DPDPE in the [(35)S]GTPgammaS functional assay in hDOR-CHO membranes. The new, highly potent, conformationally constrained antagonist may be a valuable pharmacological tool in understanding the structural and topographical requirements of peptide ligand binding to the delta-opioid receptors.