Potential Therapeutic Targets for the Treatment of Pathological Pain

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

Deadline for manuscript submissions: 30 November 2024 | Viewed by 8621

Special Issue Editor


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Guest Editor
Department of Biochemistry and Molecular Biology, Centre of Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil
Interests: analgesics; nociception; inflammatory pain; neuropathic pain; dysfunctional or nociplastic pain; pharmacological targets; signalling pathways
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Special Issue Information

Dear Colleagues,

As one of the most common reasons people seek medical care, pain is an issue of extreme relevance. Pathological pain, such as chronic inflammatory, neuropathic, and dysfunctional or nociplastic pain impairs the life quality of patients, leading to the development of anxiety, depression, labour capacity loss, and even distancing from family members and society. Often, the analgesic drugs used clinically present limited efficacy and cause various adverse effects, including analgesic tolerance, dependency, and abuse possibility, limiting their use. Thus, identifying potential therapeutic targets for treating pathological pain is highly relevant for developing more effective and safe analgesic drugs for adequate pain relief. This Special Issue is intended to investigate potential therapeutic targets for developing new analgesics, the signalling pathways involved in these processes, and the analgesic effect of synthetic drugs or natural products in pathological pain models.

We look forward to receiving your contributions.

Dr. Sara Marchesan De Oliveira
Guest Editor

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Keywords

  • analgesics
  • pathological pain models
  • inflammation
  • rheumatoid arthritis
  • neuropathy
  • nerve injuries
  • spinal cord injuries
  • antineoplastics
  • headaches
  • irritable bowel syndrome
  • fibromyalgia

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Published Papers (2 papers)

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18 pages, 5947 KiB  
Article
Kinin B2 Receptor Mediates Cisplatin-Induced Painful Peripheral Neuropathy by Intracellular Kinase Pathways and TRPA1 Channel Sensitisation
by Gabriela Becker, Maria Fernanda Pessano Fialho, Evelyne Silva Brum and Sara Marchesan Oliveira
Pharmaceuticals 2023, 16(7), 959; https://doi.org/10.3390/ph16070959 - 4 Jul 2023
Cited by 3 | Viewed by 1370
Abstract
Chemotherapy-induced peripheral neuropathy is a severe clinical problem frequently associated with cisplatin use. Although its pathophysiology is poorly understood, it is known that kinin receptors and the transient receptor potential ankyrin 1 (TRPA1) channel play a significant role in the peripheral neuropathy induced [...] Read more.
Chemotherapy-induced peripheral neuropathy is a severe clinical problem frequently associated with cisplatin use. Although its pathophysiology is poorly understood, it is known that kinin receptors and the transient receptor potential ankyrin 1 (TRPA1) channel play a significant role in the peripheral neuropathy induced by cisplatin in rodents. However, the role of signalling pathways downstream from B2 kinin receptors activation and sensitisation of the TRPA1 channel remains unknown in this model. The cisplatin-induced neuropathy model caused mechanical and cold allodynia in male Swiss mice. Antagonists for kinin B2 and B1 receptors and the TRPA1 channel attenuated the painful parameters. Local sub-nociceptive doses of kinin B2 receptor (bradykinin) and TRPA1 channel (allyl isothiocyanate; AITC) agonists enhanced the painful parameters in cisplatin-treated mice, which their respective antagonists attenuated. Furthermore, we demonstrated the interaction between the kinin B2 receptor and the TRPA1 channel in cisplatin-induced peripheral neuropathy since phospholipase C (PLC) and protein kinase C epsilon (PKCε) inhibitors attenuated the increase in mechanical and cold allodynia evoked by bradykinin and AITC in cisplatin-treated mice. Therefore, regulating the activation of signalling pathways downstream from the kinin B2 receptors activation and TRPA1 channel sensitisation can mitigate the painful peripheral neuropathy decurrent of the oncology treatment with cisplatin. Full article
(This article belongs to the Special Issue Potential Therapeutic Targets for the Treatment of Pathological Pain)
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17 pages, 1148 KiB  
Review
The Importance of Visceral Hypersensitivity in Irritable Bowel Syndrome—Plant Metabolites in IBS Treatment
by Ewa Dudzińska, Andreas M. Grabrucker, Paweł Kwiatkowski, Robert Sitarz and Monika Sienkiewicz
Pharmaceuticals 2023, 16(10), 1405; https://doi.org/10.3390/ph16101405 - 3 Oct 2023
Cited by 1 | Viewed by 6494
Abstract
The visceral stimuli from the digestive tract are transmitted via afferent nerves through the spinal cord to the brain, where they are felt as pain. The overreaction observed in the brain of irritable bowel syndrome (IBS) patients may be due to increased peripheral [...] Read more.
The visceral stimuli from the digestive tract are transmitted via afferent nerves through the spinal cord to the brain, where they are felt as pain. The overreaction observed in the brain of irritable bowel syndrome (IBS) patients may be due to increased peripheral sensitivity to stimuli from the gastrointestinal tract. Although the exact pathway is uncertain, attenuation of visceral hypersensitivity is still of interest in treating IBS. It has been shown that stress stimulates the sympathetic nervous system while inhibiting the vagus nerve (VN). In addition, stress factors lead to dysbiosis and chronic low-grade inflammation of the intestinal mucosa, which can lead to lower gastrointestinal visceral hypersensitivity. Therefore, an important goal in the treatment of IBS is the normalization of the intestinal microflora. An interesting option seems to be nutraceuticals, including Terminalia chebula, which has antibacterial and antimicrobial activity against various pathogenic Gram-positive and Gram-negative bacteria. Additionally, short-term transcutaneous vagus nerve stimulation can reduce the stress-induced increase in intestinal permeability, thereby reducing inflammation. The conducted studies also indicate a relationship between the stimulation of the vagus nerve (VN) and the activation of neuromodulatory networks in the central nervous system. Therefore, it seems reasonable to conclude that a two-way action through stimulating the VN and using nutraceuticals may become an effective therapy in treating IBS. Full article
(This article belongs to the Special Issue Potential Therapeutic Targets for the Treatment of Pathological Pain)
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