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Novel Antinociceptive Agents against Persistent Pain

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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 4694

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Special Issue Editor

Dr. Laura Micheli

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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
Special Issues, Collections and Topics in MDPI journals

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 This Special Issue of Molecules welcomes previously unpublished manuscripts covering all aspects of the pharmacology and chemistry of antinociceptive drugs, in particular the development of novel pain-relieving molecules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

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

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

Published Papers (3 papers)

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Research

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16 pages, 2210 KiB

Open AccessArticle

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 - 03 Jan 2023

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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 models as well as in vitro studies on Chinese hamster ovary (CHO) cells expressing human mu, delta, or kappa opioid receptors (CHO_hMOP, CHO_hDOP, and CHO_hKOP, 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 CHO_hMOP and CHO_hDOP, 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

Open AccessArticle

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 - 07 Nov 2022

Cited by 1 | Viewed by 1979

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 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

Open AccessReview

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

Viewed by 718

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, 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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