Novel Analgesics with Peripheral Targets

Overview

Journal Neurotherapeutics

Specialty Neurology

Date 2020 Oct 16

PMID 33063247

Citations 7

Authors

Cosmin I Ciotu

Michael J M Fischer

Affiliations

Soon will be listed here.

Abstract

A limited number of peripheral targets generate pain. Inflammatory mediators can sensitize these. The review addresses targets acting exclusively or predominantly on sensory neurons, mediators involved in inflammation targeting sensory neurons, and mediators involved in a more general inflammatory process, of which an analgesic effect secondary to an anti-inflammatory effect can be expected. Different approaches to address these systems are discussed, including scavenging proinflammatory mediators, applying anti-inflammatory mediators, and inhibiting proinflammatory or facilitating anti-inflammatory receptors. New approaches are contrasted to established ones; the current stage of progress is mentioned, in particular considering whether there is data from a molecular and cellular level, from animals, or from human trials, including an early stage after a market release. An overview of publication activity is presented, considering a IuPhar/BPS-curated list of targets with restriction to pain-related publications, which was also used to identify topics.

Citing Articles

Nutraceutical and Medicinal Importance of Marine Molluscs.

Ngandjui Y, Kereeditse T, Kamika I, Madikizela L, Makudali Msagati T Mar Drugs. 2024; 22(5).

PMID: 38786591 PMC: 11123371. DOI: 10.3390/md22050201.

Potentiating TRPA1 by Sea Anemone Peptide Ms 9a-1 Reduces Pain and Inflammation in a Model of Osteoarthritis.

Maleeva E, Palikova Y, Palikov V, Kazakov V, Simonova M, Logashina Y Mar Drugs. 2023; 21(12).

PMID: 38132938 PMC: 10744431. DOI: 10.3390/md21120617.

Identification of key factors driving inflammation-induced sensitization of muscle sensory neurons.

Nagaraja S, Tewari S, Reifman J Front Neurosci. 2023; 17:1147437.

PMID: 37250415 PMC: 10213456. DOI: 10.3389/fnins.2023.1147437.

Characterization of the Synergistic Effect between Ligands of Opioid and Free Fatty Acid Receptors in the Mouse Model of Colitis.

Binienda A, Makaro A, Talar M, Krajewska J, Tarasiuk A, Bartoszek A Molecules. 2021; 26(22).

PMID: 34833919 PMC: 8626023. DOI: 10.3390/molecules26226827.

Th2 Modulation of Transient Receptor Potential Channels: An Unmet Therapeutic Intervention for Atopic Dermatitis.

Meng J, Li Y, Fischer M, Steinhoff M, Chen W, Wang J Front Immunol. 2021; 12:696784.

PMID: 34276687 PMC: 8278285. DOI: 10.3389/fimmu.2021.696784.

References

Meves H . The action of prostaglandins on ion channels. Curr Neuropharmacol. 2008; 4(1):41-57. PMC: 2430679. DOI: 10.2174/157015906775203048. View

Richter F, Natura G, Ebbinghaus M, Segond von Banchet G, Hensellek S, Konig C . Interleukin-17 sensitizes joint nociceptors to mechanical stimuli and contributes to arthritic pain through neuronal interleukin-17 receptors in rodents. Arthritis Rheum. 2012; 64(12):4125-34. DOI: 10.1002/art.37695. View

Sung K, Kirby M, McDonald M, Lovinger D, Delpire E . Abnormal GABAA receptor-mediated currents in dorsal root ganglion neurons isolated from Na-K-2Cl cotransporter null mice. J Neurosci. 2000; 20(20):7531-8. PMC: 6772871. View

Lis K, Kuzawinska O, Balkowiec-Iskra E . Tumor necrosis factor inhibitors - state of knowledge. Arch Med Sci. 2015; 10(6):1175-85. PMC: 4296073. DOI: 10.5114/aoms.2014.47827. View

Kingwell K . Nav1.7 withholds its pain potential. Nat Rev Drug Discov. 2019; . DOI: 10.1038/d41573-019-00065-0. View

Lai Y, Dong C . Therapeutic antibodies that target inflammatory cytokines in autoimmune diseases. Int Immunol. 2015; 28(4):181-8. PMC: 4889878. DOI: 10.1093/intimm/dxv063. View

Poet M, Kornak U, Schweizer M, Zdebik A, Scheel O, Hoelter S . Lysosomal storage disease upon disruption of the neuronal chloride transport protein ClC-6. Proc Natl Acad Sci U S A. 2006; 103(37):13854-9. PMC: 1564226. DOI: 10.1073/pnas.0606137103. View

Gardiner N, Cafferty W, Slack S, Thompson S . Expression of gp130 and leukaemia inhibitory factor receptor subunits in adult rat sensory neurones: regulation by nerve injury. J Neurochem. 2002; 83(1):100-9. DOI: 10.1046/j.1471-4159.2002.01101.x. View

Gomtsyan A, McDonald H, Schmidt R, Daanen J, Voight E, Segreti J . TRPV1 ligands with hyperthermic, hypothermic and no temperature effects in rats. Temperature (Austin). 2016; 2(2):297-301. PMC: 4843892. DOI: 10.1080/23328940.2015.1046013. View

10.

Wang X, Yu X, Yan X, Lei F, Chai Y, Jiang J . TRPM8 in the negative regulation of TNFα expression during cold stress. Sci Rep. 2017; 7:45155. PMC: 5362914. DOI: 10.1038/srep45155. View

11.

Takasaki I, Nakamura K, Shimodaira A, Watanabe A, Du Nguyen H, Okada T . The novel small-molecule antagonist of PAC1 receptor attenuates formalin-induced inflammatory pain behaviors in mice. J Pharmacol Sci. 2018; 139(2):129-132. DOI: 10.1016/j.jphs.2018.11.011. View

12.

Matsunaga M, Yamauchi P . IL-4 and IL-13 Inhibition in Atopic Dermatitis. J Drugs Dermatol. 2016; 15(8):925-9. View

13.

Li M, Shi J, Tang J, Chen D, Ai B, Chen J . Effects of complete Freund's adjuvant on immunohistochemical distribution of IL-1beta and IL-1R I in neurons and glia cells of dorsal root ganglion. Acta Pharmacol Sin. 2005; 26(2):192-8. DOI: 10.1111/j.1745-7254.2005.00522.x. View

14.

Burmester G, McInnes I, Kremer J, Miranda P, Korkosz M, Vencovsky J . A randomised phase IIb study of mavrilimumab, a novel GM-CSF receptor alpha monoclonal antibody, in the treatment of rheumatoid arthritis. Ann Rheum Dis. 2017; 76(6):1020-1030. DOI: 10.1136/annrheumdis-2016-210624. View

15.

Ahn A, Basbaum A . Where do triptans act in the treatment of migraine?. Pain. 2005; 115(1-2):1-4. PMC: 1850935. DOI: 10.1016/j.pain.2005.03.008. View

16.

Sachs D, Villarreal C, Cunha F, Parada C, Ferreira S . The role of PKA and PKCepsilon pathways in prostaglandin E2-mediated hypernociception. Br J Pharmacol. 2009; 156(5):826-34. PMC: 2697751. DOI: 10.1111/j.1476-5381.2008.00093.x. View

17.

Carr R, Sittl R, Fleckenstein J, Grafe P . GABA increases electrical excitability in a subset of human unmyelinated peripheral axons. PLoS One. 2010; 5(1):e8780. PMC: 2808338. DOI: 10.1371/journal.pone.0008780. View

18.

Ji R, Samad T, Jin S, Schmoll R, Woolf C . p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia. Neuron. 2002; 36(1):57-68. DOI: 10.1016/s0896-6273(02)00908-x. View

19.

Lee Y, Zachrisson O, Tonge D, McNaughton P . Upregulation of bradykinin B2 receptor expression by neurotrophic factors and nerve injury in mouse sensory neurons. Mol Cell Neurosci. 2002; 19(2):186-200. DOI: 10.1006/mcne.2001.1073. View

20.

Patel R, Montagut-Bordas C, Dickenson A . Calcium channel modulation as a target in chronic pain control. Br J Pharmacol. 2017; 175(12):2173-2184. PMC: 5980588. DOI: 10.1111/bph.13789. View