Pain
Michele Barletta, Jane Quandt, Rachel Reed in Equine Anesthesia and Pain Management, 2023
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
Mark J. Ashley, David A. Hovda in Traumatic Brain Injury, 2017
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 of opioids: basic pharmacology
Nigel Sykes, Michael I Bennett, Chun-Su Yuan in Clinical Pain Management, 2008
Opioid peptides are endogenously produced predominantly in the central nervous system and the spinal cord.37 The three distinct families of peptides, endorphins, enkephalins, and dynorphins, are natural agonist ligands for opioid receptors mu, delta, and kappa, respectively (Table 12.1).35 Each family of opioid peptides is derived from a distinct precursor molecule, with proopiomelanocortin, proenkephalin, and prodynorphin being precursors of endorphins, enkephalins, and dynorphins, respectively. Of the relatively newly discovered endogenous opioid-related peptides, endomorphin-1 and -2 are selective, potent mu-receptor agonists that demonstrate a significant degree of analgesic activity.42, 43 Endomorphin-1 at equianalgesic doses appears to cause less severe respiratory depression compared with other mu agonists,43 suggesting that it may act on specific mu receptor subtypes.44 Another notable endogenous peptide orphanin NQ/nociceptin, a ligand to receptor ORL-1, plays a complex role in producing analgesia and is being investigated.45
Neuropharmacological basis for multimodal analgesia in chronic pain
Published in Postgraduate Medicine, 2022
Ryan Patel, Anthony H Dickenson
The pain-relieving properties of naturally occurring opioids have been utilized for centuries, and today opioids remain the mainstay of treating acute and chronic pain. Morphine has become the gold standard analgesic to which all others are compared. The classical opioid receptors μ, δ and κ are G-protein coupled, and later a fourth opioid-like receptor (ORL1) was described and renamed the nociceptin receptor. Soon after, a series of endogenous peptide ligands were described. Most of these bind to multiple receptors through endomorphin-1/2 and β-endorphin have highest affinity for μ-opioid receptors, met- and leu-enkephalin have highest affinity δ-opioid receptors, dynorphin A/B have highest affinity κ-opioid receptors, and nociceptin/orphanin FQ has highest affinity for the nociceptin receptor [69]. Upon receptor activation neuronal excitability or action potential propagation is inhibited by several mechanisms including opening of G protein–coupled inwardly rectifying potassium channels [70], inhibition of sodium [71] and calcium channels [72], and inhibition of Ih currents [73].
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.
Related Knowledge Centers
- Brainstem
- Central Nervous System
- Peripheral Nervous System
- Protein Tertiary Structure
- Tetrapeptide
- Amino Acid
- Neurotransmitter
- Opioid
- Μ-Opioid Receptor
- Neuron