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Pharmaceuticals
Special Issues
Drug Candidates for the Treatment of Pain
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Drug Candidates for the Treatment of Pain

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 12251

Special Issue Editors

Dr. William Raffaeli

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Guest Editor
ISAL Foundation, Institute for Pain Research, 47923 Rimini, Italy
Interests: pain research; pain assesement; pain management; pain biomarker; opioid and immunity; pheripheral opioid receptor; epiduroscopy; pain treatment
Dr. Carolina Muscoli

E-Mail Website
Guest Editor
Institute of Research for Food Safety & Health (IRC-FSH), Department of Health Sciences, University “Magna Graecia” of Catanzaro, Viale Europa, Loc. Germaneto, 88100 Catanzaro, Italy
Interests: pain assessment; pain management; pain biomarker; free radicals in pain; antioxidants; pain epigenetics; nutraceuticals for pain management
Special Issues, Collections and Topics in MDPI journals
Dr. Dominique Massotte

E-Mail Website
Guest Editor
French National Centre for Scientific Research, Institut des Neurosciences Cellulaires et Intégratives, University of Strasbourg, 67000 Strasbourg, France
Interests: opioid system; opioid receptors; G protein-coupled receptor trafficking and signaling; G protein-coupled receptor heteromerization; G protein-coupled receptor in addiction or chronic pain (preclinical models)

Special Issue Information

Dear Colleagues,

Pain is a serious public health issue worldwide. It affects 1 in 5 people both in the United States and in Europe, producing dramatic biological, physical, psychological, and social consequences on affected patients, as well as a great economic load on healthcare systems and societies.

Nevertheless, pain is often an inadequately treated problem. NSAIDs have often a limited efficacy, while the use of opioids is limited by the risk of addiction, the development of tolerance, and vulnerability to hyperalgesia. Moreover, for many pathologies (e.g., fibromyalgia, phantom pain), there is still a lack of effective analgesics.

There is a critical need for effective new drugs for pain that can maintain efficacy over long-term treatment regimens without the risk of tolerance, addiction, and other negative side-effects. Further, understanding the underlying mechanism causing pain is crucial for the development of novel therapeutics and also for the ability to recognize which type of analgesic to prescribe to pain patients.

In this Special Issue, the state of the art related to research on recent candidate drugs for the treatment of pain is presented, together with an analysis of emerging targets for pain treatment, with the aim to provide researchers with the most cutting-edge information in this field.

Dr. William Raffaeli
Prof. Carolina Muscoli
Dr. Dominique Massotte
Guest Editors

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. Pharmaceuticals is an international peer-reviewed open access monthly 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 2900 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
  • pharmacological therapy
  • analgesic drugs
  • innovative pain drugs
  • pain therapy

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Published Papers (3 papers)

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Research

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17 pages, 3262 KiB  
Article
Development of Capsaicin-Containing Analgesic Silicone-Based Transdermal Patches
by Szabolcs László, István Z. Bátai, Szilvia Berkó, Erzsébet Csányi, Ágnes Dombi, Gábor Pozsgai, Kata Bölcskei, Lajos Botz, Ödön Wagner and Erika Pintér
Pharmaceuticals 2022, 15(10), 1279; https://doi.org/10.3390/ph15101279 - 18 Oct 2022
Cited by 10 | Viewed by 3559
Abstract
Transdermal therapeutic systems (TTSs) enable convenient dosing in drug therapy. Modified silicone-polymer-based patches are well-controlled and cost-effective matrix diffusion systems. In the present study, we investigated the substance release properties, skin penetration, and analgesic effect of this type of TTS loaded with low-dose [...] Read more.
Transdermal therapeutic systems (TTSs) enable convenient dosing in drug therapy. Modified silicone-polymer-based patches are well-controlled and cost-effective matrix diffusion systems. In the present study, we investigated the substance release properties, skin penetration, and analgesic effect of this type of TTS loaded with low-dose capsaicin. Release properties were measured in Franz diffusion cell and continuous flow-through cell approaches. Capsaicin was detected with HPLC-UV and UV spectrophotometry. Raman spectroscopy was conducted on human skin samples exposed to the TTS. A surgical incision or carrageenan injection was performed on one hind paw of male Wistar rats. TTSs were applied to the epilated dorsal skin. Patches were kept on the animals for 6 h. The thermal hyperalgesia and mechanical pain threshold of the hind paws were detected. Patches exhibited controlled, zero-order kinetic capsaicin release. According to the Raman mapping, capsaicin penetrated into the epidermis and dermis of human skin, where the target receptors are expressed. The thermal pain threshold drop of the operated rat paws was reversed by capsaicin treatment compared to that of animals treated with control patches. It was concluded that our modified silicone-polymer-based capsaicin-containing TTS is suitable for the relief of traumatic and inflammatory pain. Full article
(This article belongs to the Special Issue Drug Candidates for the Treatment of Pain)
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24 pages, 6352 KiB  
Article
Differential Effects of a Novel Opioid Ligand UTA1003 on Antinociceptive Tolerance and Motor Behaviour
by Alok K. Paul, Krystel L. Woolley, Mohammed Rahmatullah, Polrat Wilairatana, Jason A. Smith, Nuri Gueven and Nikolas Dietis
Pharmaceuticals 2022, 15(7), 789; https://doi.org/10.3390/ph15070789 - 24 Jun 2022
Cited by 1 | Viewed by 2805
Abstract
Analgesic tolerance is a major problem in the clinic for the maintenance of opioid-induced long-term pain relief. Opioids with mixed activity on multiple opioid receptors promise reduced antinociceptive tolerance in preclinical studies, but these compounds typically show poor bioavailability upon oral, subcutaneous, intraperitoneal, [...] Read more.
Analgesic tolerance is a major problem in the clinic for the maintenance of opioid-induced long-term pain relief. Opioids with mixed activity on multiple opioid receptors promise reduced antinociceptive tolerance in preclinical studies, but these compounds typically show poor bioavailability upon oral, subcutaneous, intraperitoneal, or intravenous administration. We designed UTA1003 as a novel opioid that acts as a mu (MOP) and kappa (KOP) opioid receptor agonist and a partial agonist for delta (DOP) opioid receptor. In the present study, its antinociceptive effects, as well as its effects on antinociceptive tolerance and motor behaviour, were investigated in male rats. Acute antinociception was measured before (basal) and at different time points after subcutaneous injection of UTA1003 or morphine using the tail flick and hot plate assays. Various motor behavioural activities, including horizontal locomotion, rearing, and turning, were automatically measured in an open-field arena. The antinociceptive and behavioural effects of repeated administration of UTA1003 and morphine were determined over eight days. UTA1003 induced mild antinociceptive effects after acute administration but induced no tolerance after repeated treatment. Importantly, UTA1003 co-treatment with morphine prevented antinociceptive tolerance compared to morphine alone. UTA1003 showed less motor suppression than morphine in both acute and sub-chronic treatment regimens, while it did not affect morphine-induced motor suppression or hyper-excitation. Based on these activities, we speculate that UTA1003 crosses the blood-brain barrier after subcutaneous administration and, therefore, could be developed as a lead molecule to avoid opioid-induced antinociceptive tolerance and motor suppression. Further structural modifications to improve its antinociceptive effects, toxicity profile, and ADME parameters are nevertheless required. Full article
(This article belongs to the Special Issue Drug Candidates for the Treatment of Pain)
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Review

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11 pages, 271 KiB  
Review
Vulvodynia: Pain Management Strategies
by Lucia Merlino, Luca Titi, Francesco Pugliese, Giulia D’Ovidio, Roberto Senatori, Carlo Della Rocca and Maria Grazia Piccioni
Pharmaceuticals 2022, 15(12), 1514; https://doi.org/10.3390/ph15121514 - 5 Dec 2022
Cited by 6 | Viewed by 4767
Abstract
Background: Vulvodynia is defined in this international consensus as persistent vulvar pain that occurs for >3 months without an identifiable cause and with several potential associated factors. At present there is no univocal consensus in the therapeutic treatment of vulvodynia. The methods of [...] Read more.
Background: Vulvodynia is defined in this international consensus as persistent vulvar pain that occurs for >3 months without an identifiable cause and with several potential associated factors. At present there is no univocal consensus in the therapeutic treatment of vulvodynia. The methods of intervention are based on various aspects including, above all, the management of painful symptoms. Methods: a research on scientific database such as “Pubmed”, “Medline Plus”, “Medscape” was conducted, using the words “women’s genital pain” and “vulvodynia” for the review of the scientific evidence on the assessment and treatment of women’s genital pain. Results: Among the drugs with pain-relieving action, the most effective in the treatment of vulvodynia would seem to be those with antidepressant and anticonvulsant action, even if their mechanisms of action are not known and there are still insufficient studies able to demonstrate their real validity. Among the least effective are non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids. However, the ideal would seem to use a combined treatment with multiple types of drugs. Conclusions: Future studies are needed to draw up a unique therapeutic action plan that considers the stratification of patients with vulvodynia and the variability of the symptom. Full article
(This article belongs to the Special Issue Drug Candidates for the Treatment of Pain)
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