Targeting Members of the Chemokine Family as a Novel Approach to Treating Neuropathic Pain
Neuropathic pain is a debilitating condition that affects millions of people worldwide. Numerous studies indicate that this type of pain is a chronic condition with a complex mechanism that tends to worsen over time, leading to a significant deterioration in patients’ quality of life and issues like...
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| Format: | Article |
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MDPI AG
2023-07-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/15/5766 |
| _version_ | 1797586330413170688 |
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| author | Katarzyna Pawlik Joanna Mika |
| author_facet | Katarzyna Pawlik Joanna Mika |
| author_sort | Katarzyna Pawlik |
| collection | DOAJ |
| description | Neuropathic pain is a debilitating condition that affects millions of people worldwide. Numerous studies indicate that this type of pain is a chronic condition with a complex mechanism that tends to worsen over time, leading to a significant deterioration in patients’ quality of life and issues like depression, disability, and disturbed sleep. Presently used analgesics are not effective enough in neuropathy treatment and may cause many side effects due to the high doses needed. In recent years, many researchers have pointed to the important role of chemokines not only in the development and maintenance of neuropathy but also in the effectiveness of analgesic drugs. Currently, approximately 50 chemokines are known to act through 20 different seven-transmembrane G-protein-coupled receptors located on the surface of neuronal, glial, and immune cells. Data from recent years clearly indicate that more chemokines than initially thought (CCL1/2/3/5/7/8/9/11, CXCL3/9/10/12/13/14/17; XCL1, CX3CL1) have pronociceptive properties; therefore, blocking their action by using neutralizing antibodies, inhibiting their synthesis, or blocking their receptors brings neuropathic pain relief. Several of them (CCL1/2/3/7/9/XCL1) have been shown to be able to reduce opioid drug effectiveness in neuropathy, and neutralizing antibodies against them can restore morphine and/or buprenorphine analgesia. The latest research provides irrefutable evidence that chemokine receptors are promising targets for pharmacotherapy; chemokine receptor antagonists can relieve pain of different etiologies, and most of them are able to enhance opioid analgesia, for example, the blockade of CCR1 (J113863), CCR2 (RS504393), CCR3 (SB328437), CCR4 (C021), CCR5 (maraviroc/AZD5672/TAK-220), CXCR2 (NVPCXCR220/SB225002), CXCR3 (NBI-74330/AMG487), CXCR4 (AMD3100/AMD3465), and XCR1 (vMIP-II). Recent research has shown that multitarget antagonists of chemokine receptors, such as CCR2/5 (cenicriviroc), CXCR1/2 (reparixin), and CCR2/CCR5/CCR8 (RAP-103), are also very effective painkillers. A multidirectional strategy based on the modulation of neuronal–glial–immune interactions by changing the activity of the chemokine family can significantly improve the quality of life of patients suffering from neuropathic pain. However, members of the chemokine family are still underestimated pharmacological targets for pain treatment. In this article, we review the literature and provide new insights into the role of chemokines and their receptors in neuropathic pain. |
| first_indexed | 2024-03-11T00:20:46Z |
| format | Article |
| id | doaj.art-aee396a730484548a7e40a85c064ae17 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T00:20:46Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-aee396a730484548a7e40a85c064ae172023-11-18T23:18:36ZengMDPI AGMolecules1420-30492023-07-012815576610.3390/molecules28155766Targeting Members of the Chemokine Family as a Novel Approach to Treating Neuropathic PainKatarzyna Pawlik0Joanna Mika1Department of Pain Pharmacology, Maj Institute of Pharmacology Polish Academy of Sciences, 12 Smetna Str., 31-343 Cracow, PolandDepartment of Pain Pharmacology, Maj Institute of Pharmacology Polish Academy of Sciences, 12 Smetna Str., 31-343 Cracow, PolandNeuropathic pain is a debilitating condition that affects millions of people worldwide. Numerous studies indicate that this type of pain is a chronic condition with a complex mechanism that tends to worsen over time, leading to a significant deterioration in patients’ quality of life and issues like depression, disability, and disturbed sleep. Presently used analgesics are not effective enough in neuropathy treatment and may cause many side effects due to the high doses needed. In recent years, many researchers have pointed to the important role of chemokines not only in the development and maintenance of neuropathy but also in the effectiveness of analgesic drugs. Currently, approximately 50 chemokines are known to act through 20 different seven-transmembrane G-protein-coupled receptors located on the surface of neuronal, glial, and immune cells. Data from recent years clearly indicate that more chemokines than initially thought (CCL1/2/3/5/7/8/9/11, CXCL3/9/10/12/13/14/17; XCL1, CX3CL1) have pronociceptive properties; therefore, blocking their action by using neutralizing antibodies, inhibiting their synthesis, or blocking their receptors brings neuropathic pain relief. Several of them (CCL1/2/3/7/9/XCL1) have been shown to be able to reduce opioid drug effectiveness in neuropathy, and neutralizing antibodies against them can restore morphine and/or buprenorphine analgesia. The latest research provides irrefutable evidence that chemokine receptors are promising targets for pharmacotherapy; chemokine receptor antagonists can relieve pain of different etiologies, and most of them are able to enhance opioid analgesia, for example, the blockade of CCR1 (J113863), CCR2 (RS504393), CCR3 (SB328437), CCR4 (C021), CCR5 (maraviroc/AZD5672/TAK-220), CXCR2 (NVPCXCR220/SB225002), CXCR3 (NBI-74330/AMG487), CXCR4 (AMD3100/AMD3465), and XCR1 (vMIP-II). Recent research has shown that multitarget antagonists of chemokine receptors, such as CCR2/5 (cenicriviroc), CXCR1/2 (reparixin), and CCR2/CCR5/CCR8 (RAP-103), are also very effective painkillers. A multidirectional strategy based on the modulation of neuronal–glial–immune interactions by changing the activity of the chemokine family can significantly improve the quality of life of patients suffering from neuropathic pain. However, members of the chemokine family are still underestimated pharmacological targets for pain treatment. In this article, we review the literature and provide new insights into the role of chemokines and their receptors in neuropathic pain.https://www.mdpi.com/1420-3049/28/15/5766chemokineschemokine receptorsneuropathic painbindaritantagonistagonist |
| spellingShingle | Katarzyna Pawlik Joanna Mika Targeting Members of the Chemokine Family as a Novel Approach to Treating Neuropathic Pain Molecules chemokines chemokine receptors neuropathic pain bindarit antagonist agonist |
| title | Targeting Members of the Chemokine Family as a Novel Approach to Treating Neuropathic Pain |
| title_full | Targeting Members of the Chemokine Family as a Novel Approach to Treating Neuropathic Pain |
| title_fullStr | Targeting Members of the Chemokine Family as a Novel Approach to Treating Neuropathic Pain |
| title_full_unstemmed | Targeting Members of the Chemokine Family as a Novel Approach to Treating Neuropathic Pain |
| title_short | Targeting Members of the Chemokine Family as a Novel Approach to Treating Neuropathic Pain |
| title_sort | targeting members of the chemokine family as a novel approach to treating neuropathic pain |
| topic | chemokines chemokine receptors neuropathic pain bindarit antagonist agonist |
| url | https://www.mdpi.com/1420-3049/28/15/5766 |
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