China
Africa
Explore chapters and articles related to this topic
Pain
Published in Michele Barletta, Jane Quandt, Rachel Reed, Equine Anesthesia and Pain Management, 2023
Jarred Williams, Katie Seabaugh, Molly Shepard, Dana Peroni
Another EA technique is a pattern of “mixed mode” or dense and disperse (DD) waveforms, alternating between high (~100 Hz) and low (2 Hz) frequency. For example, the pulse generator connected to two acupoints would apply a square wave at 2 Hz for 3 seconds then immediately switch to 100 Hz for 3 seconds, and then back to low frequency, and so on.This EA technique has been shown to stimulate more significant endogenous release of endomorphin (mu agonist) as well as dynorphin A, a neurotransmitter shown to reduce pain behavior in acute, neuropathic, and inflammatory models.This technique has been shown to reduce postoperative opioid requirements in people, and improve pain scores in chronic human pain states such as diabetic neuropathy and lower back pain.
Neurotransmitters and pharmacology
Published in Mark J. Ashley, David A. Hovda, Traumatic Brain Injury, 2017
Ronald A. Browning, Richard W. Clough
The first discovered opioid peptides were the pentapeptides (containing five amino acids), leucine-enkephalin, and methionine-enkephalin, which were isolated by Hughes et al.202 Although there may be other families of opioid peptides, current interest is focused on three separate families of opioid peptides, each derived from a separate gene family.203 These include 1) the enkephalins (pentapeptides derived from a proenkephalin precursor), 2) the endorphins (e.g., β-endorphin, a 31 amino acid-containing peptide derived from proopiomelanocortin or POMC), and 3) the dynorphins (8 to 13 amino acid-containing peptides derived from a prodynorphin precursor). Three other endogenous opioid peptides have more recently been discovered and are known as orphanin FQ, endomorphin-1, and endomorphin-2. Orphanin FQ, also known as nociceptin, has effects opposite those of morphine and is referred to as pronociceptive (see section on opioid receptors). Much current research is focused on whether the endormorphins are selective mu agonists, but because there is relatively little known about the edomorphin peptides, we focus our discussion on the enkephalins, endorphins, and dynorphins.
Clinical pharmacology: opioids
Published in Pamela E Macintyre, Suellen M Walker, David J Rowbotham, Clinical Pain Management, 2008
David J Rowbotham, Alcira Serrano-Gomez, Anne Heffernan
Endogenous ligands acting at opioid receptors include enkephalins (δ receptor), dynorphins (κ receptor), endorphins (high affinity, but poor selectivity for μ receptors),41 and nociceptin/orphanin FQ (NOP receptor, see below under Nociceptin/orphanin FQ receptor). The endogenous selective ligands for the μ receptor (endomorphins) were first identified in 1997.29 Both endomorphin 1 and endomorphin 2 are peptides of four amino acids and intimately involved in nociceptive pathways.42 Unlike the other recognized peptides, precursors for endomorphin 1 and 2 have not been identified.
New concepts in opioid analgesia
Published in Expert Opinion on Investigational Drugs, 2018
Endogenous opioid peptides are derived from the precursors proopiomelanocortin (encoding beta-endorphin), proenkephalin (encoding Met-enkephalin and Leu-enkephalin), and prodynorphin (encoding dynorphins). These peptides contain the common Tyr-Gly-Gly-Phe-Met/Leu sequence at their amino terminals, known as the opioid motif. Beta-endorphin and the enkephalins are antinociceptive agents acting at mu- and delta-opioid receptors. Dynorphins can elicit both pro- and antinociceptive effects via N-methyl-D-aspartate receptors and kappa-opioid receptors, respectively. A fourth group of tetrapeptides (endomorphins) with yet unknown precursors do not contain the pan-opioid motif but bind to mureceptors with high selectivity. Opioid peptides are expressed throughout the central and peripheral nervous systems, in neuroendocrine tissues, and in immune cells [10,11,13,15]. Interactions between immune cell-derived opioid peptides and peripheral opioid receptors have been examined extensively, particularly with regard to the generation of analgesia [9–11].
Nanotechnology application for pain therapy
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Mahmoud Reza Moradkhani, Arash Karimi, Babak Negahdari
Hua and Cabot also reported the use of targeted nanoparticles to deliver opioids, in particular, loperamide HCl, specifically to peripheral opioid receptors to stimulate analgesic and anti-inflammatory actions for use in painful inflammatory conditions [18]. Ward et al. also reported other sustained engineered release systems to extend the duration of action of opioid analgesics [19]. Liu and colleagues in their report demonstrated that endomorphin-1, adsorbed onto the surface of butyl- cyanoacrylate nanoparticles and coated with polysorbate 80 could be administered intravenously as an analgesic agent [20]. Furthermore, Tosi and co-worker investigated the antinociceptive efficacy of peptide-derivatized nanoparticles loaded with loperamide HCl in an in vivo experiment for delivery to central opioid receptors. They concluded that there was a peak percentage of possible effect of 60% at 4 h and a significant continued release effect for 6 h after the administration of 0.7 mg of loperamide HCl in Wistar rats [21]. In addition, Chen et al. reported that nanoparticles made up of loperamide and PLGA-PEG-PLGA triblock copolymer coated with poloxamer 188 or polysorbate 80 enhanced penetrations across the blood–brain barrier in comparison to PLGA-PEG-PLGA nanoparticles and PLGA nanoparticles.
Antinociceptive potency of a fluorinated cyclopeptide Dmt-c[D-Lys-Phe-p-CF3-Phe-Asp]NH2
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2018
Justyna Piekielna-Ciesielska, Adriano Mollica, Stefano Pieretti, Jakub Fichna, Agata Szymaszkiewicz, Marta Zielińska, Radzisław Kordek, Anna Janecka
Anti-nociception was studied in the hot-plate test in mice after i.c.v. or i.v. administration of peptides. The results obtained in the dose-response studies after i.c.v. administration are shown in Figure 1(A). Both tested compounds showed dose-dependent anti-nociceptive activity, significantly stronger than that of endomorphin-2 (EM-2). The ED50 values (jumping response) for C-36 and F-81 were 57.78 and 17.27 ng, respectively, indicating that F-81 was approximately threefold more potent than C-36 (Figure 1(A)). In order to investigate if these peptides are able to cross the BBB, peripheral i.v. administration of the peptides was performed, and the results are reported in Figure 1(B). After i.v. administration at the dose of 20 mg/kg, only a negligible anti-nociceptive activity was observed for both compounds (Figure 1(B)). To characterize the involvement of opioid receptors in the anti-nociceptive action of analog F-81, co-administration studies with opioid receptor antagonists were performed. The anti-nociceptive effect of F-81 (10 ng/animal, i.c.v.) was blocked by β-funaltrexamine (β-FNA, 1 µg/animal), showing the involvement of the mu opioid receptors. The delta-opioid receptor antagonist, naltrindole (NTL, 1 µg/animal), and kappa-opioid receptor antagonist, norbinaltorphimine (nor-BNI, 5 µg/animal, i.c.v.), did not modify the anti-nociceptive action of F-81 (Figure 1(C)). Even though F-81 and C-36 showed significant kappa-affinity, the obtained results are in agreement with a generally accepted fact that the anti-nociceptive effects are mainly mediated by the mu opioid receptor32,38.