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Novel Antinociceptive Agents against Persistent Pain

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 7127

Special Issue Editor


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Guest Editor
Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, 50139 Florence, Italy
Interests: pain pharmacology; chronic pain; inflammatory pain; chemotherapy induced neuropathic pain; trauma-induced neuropathic pain, glial cells; hyperalgesia; allodynia; in vivo approach; in vitro approach; therapeutic agents; pharmacological mechanism
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Special Issue Information

Dear Colleagues,

Effective pain therapy is one of society’s principal needs. Persistent and neuropathic pain represent significant clinical problems and, as chronic conditions, can cause distress and seriously affect a patient’s quality of life. This condition is often refractory to conventional therapy. Analgesics that are used to treat different persistent pain conditions are usually marked by the onset of a several side effects, and the great majority of patients obtain only partial relief. Therefore, the necessity of new analgesics is clear. Medicinal chemistry is continuously called on to face the novel challenges that arise from the steady trickle of scientific breakthroughs to discover new, increasingly safe and effective drugs. This Special Issue of Molecules welcomes previously unpublished manuscripts covering all aspects of the pharmacology and chemistry of antinociceptive drugs, in particular the development of novel pain-relieving molecules that are active against different persistent pain conditions.

Dr. Laura Micheli
Guest Editor

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Keywords

  • chronic pain
  • drug development
  • glial cells
  • inflammatory pain
  • medicinal chemistry
  • neuropathic pain
  • pain
  • pharmacodynamics
  • visceral pain

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Published Papers (3 papers)

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Research

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16 pages, 2210 KiB  
Article
A Novel Multi-Target Mu/Delta Opioid Receptor Agonist, HAGD, Produced Potent Peripheral Antinociception with Limited Side Effects in Mice and Minimal Impact on Human Sperm Motility In Vitro
by Fangfang Li, Feng Yue, Wei Zhang, Biao Xu, Yiqing Wang and Xuehong Zhang
Molecules 2023, 28(1), 427; https://doi.org/10.3390/molecules28010427 - 3 Jan 2023
Cited by 1 | Viewed by 2014
Abstract
Pain is a common clinical symptom among patients. Although various opioid analgesics have been developed, their side effects hinder their application. This study aimed to develop a novel opioid analgesic, HAGD (H-Tyr-D-AIa-GIy-Phe-NH2), with limited side effects. In vivo studies on mouse [...] Read more.
Pain is a common clinical symptom among patients. Although various opioid analgesics have been developed, their side effects hinder their application. This study aimed to develop a novel opioid analgesic, HAGD (H-Tyr-D-AIa-GIy-Phe-NH2), with limited side effects. In vivo studies on mouse models as well as in vitro studies on Chinese hamster ovary (CHO) cells expressing human mu, delta, or kappa opioid receptors (CHOhMOP, CHOhDOP, and CHOhKOP, respectively) and human sperm were conducted. Compared with subcutaneous morphine (10 mg/kg), subcutaneous HAGD (10 mg/kg) produced equipotent or even greater antinociception with a prolonged duration by activating mu/delta opioid receptors in preclinical mouse pain models. The analgesic tolerance, rewarding effects (i.e., conditioned place preference and acute hyperlocomotion), and gastrointestinal transit inhibition of HAGD were significantly reduced compared with those of morphine. Both HAGD and morphine exhibited a withdrawal response and had no impacts on motor coordination. In CHOhMOP and CHOhDOP, HAGD showed specific and efficient intracellular Ca2+ stimulation. HAGD had minimal impact on human sperm motility in vitro, whereas 1 × 10−7 and 1 × 10−8 mol/L of morphine significantly declined sperm motility at 3.5 h. Overall, HAGD may serve as a promising antinociceptive compound. Full article
(This article belongs to the Special Issue Novel Antinociceptive Agents against Persistent Pain)
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18 pages, 22730 KiB  
Article
Olfactory Stimulation Successfully Modulates the Neurochemical, Biochemical and Behavioral Phenotypes of the Visceral Pain
by Wen-Chieh Liao, Rou-An Yao, Li-You Chen, Ting-Yi Renn, Igor V. Klimenkov, Nikolay P. Sudakov, Fu-Der Mai, Yea-Tzy Chen and Hung-Ming Chang
Molecules 2022, 27(21), 7659; https://doi.org/10.3390/molecules27217659 - 7 Nov 2022
Cited by 3 | Viewed by 2399
Abstract
Visceral pain (VP) is the organ-derived nociception in which increased inflammatory reaction and exaggerated activation of the central nucleus of the amygdala (CeA) may contribute to this deficiency. Considering the amygdala also serves as the integration center for olfaction, the present study aimed [...] Read more.
Visceral pain (VP) is the organ-derived nociception in which increased inflammatory reaction and exaggerated activation of the central nucleus of the amygdala (CeA) may contribute to this deficiency. Considering the amygdala also serves as the integration center for olfaction, the present study aimed to determine whether olfactory stimulation (OS) would effectively depress over-activation and inflammatory reaction in CeA, and successfully relieve VP-induced abnormalities. Adult rats subjected to intraperitoneal injection of acetic acid inhaled lavender essential oil for 2 or 4 h. The potential benefits of OS were determined by measuring the pro-inflammatory cytokine level, intracellular potassium and the upstream small-conductance calcium-activated potassium (SK) channel expression, together with detecting the stress transmitters that participated in the modulation of CeA activity. Results indicated that in VP rats, strong potassium intensity, reduced SK channel protein level, and increased corticotropin-releasing factor, c-fos, and substance P immuno-reactivities were detected in CeA. Enhanced CeA activation corresponded well with increased inflammatory reaction and decreased locomotion, respectively. However, in rats subjected to VP and received OS, all above parameters were significantly returned to normal levels with higher change detected in treating OS of 4h. As OS successfully depresses inflammation and CeA over-activation, application of OS may serve as an alternative and effective strategy to efficiently relieve VP-induced deficiency. Full article
(This article belongs to the Special Issue Novel Antinociceptive Agents against Persistent Pain)
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Review

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37 pages, 5336 KiB  
Review
Analgesic Peptides: From Natural Diversity to Rational Design
by Katarzyna Gach-Janczak, Monika Biernat, Mariola Kuczer, Anna Adamska-Bartłomiejczyk and Alicja Kluczyk
Molecules 2024, 29(7), 1544; https://doi.org/10.3390/molecules29071544 - 29 Mar 2024
Cited by 3 | Viewed by 2154
Abstract
Pain affects one-third of the global population and is a significant public health issue. The use of opioid drugs, which are the strongest painkillers, is associated with several side effects, such as tolerance, addiction, overdose, and even death. An increasing demand for novel, [...] Read more.
Pain affects one-third of the global population and is a significant public health issue. The use of opioid drugs, which are the strongest painkillers, is associated with several side effects, such as tolerance, addiction, overdose, and even death. An increasing demand for novel, safer analgesic agents is a driving force for exploring natural sources of bioactive peptides with antinociceptive activity. Since the G protein-coupled receptors (GPCRs) play a crucial role in pain modulation, the discovery of new peptide ligands for GPCRs is a significant challenge for novel drug development. The aim of this review is to present peptides of human and animal origin with antinociceptive potential and to show the possibilities of their modification, as well as the design of novel structures. The study presents the current knowledge on structure-activity relationship in the design of peptide-based biomimetic compounds, the modification strategies directed at increasing the antinociceptive activity, and improvement of metabolic stability and pharmacodynamic profile. The procedures employed in prolonged drug delivery of emerging compounds are also discussed. The work summarizes the conditions leading to the development of potential morphine replacements. Full article
(This article belongs to the Special Issue Novel Antinociceptive Agents against Persistent Pain)
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