# Mas-Related G-Protein-Coupled Receptors: Emerging Roles in Neuropathic Pain

**Authors:** Mario García-Domínguez

PMC · DOI: 10.3390/biom16020290 · Biomolecules · 2026-02-12

## TL;DR

This paper reviews the role of Mas-related G-protein-coupled receptors in neuropathic pain and their potential as drug targets.

## Contribution

The paper highlights novel insights into how these receptors modulate pain hypersensitivity and their therapeutic potential.

## Key findings

- Mas-related GPCRs influence neuronal excitability and inflammatory responses in neuropathic pain.
- These receptors interact with ion channels and immune mediators to regulate pain signaling.
- Targeting specific receptor subtypes may lead to new analgesic therapies.

## Abstract

Mas-related G-protein-coupled receptors constitute a distinct family of GPCRs expressed in some subsets of sensory neurons and immune cells. Increasing evidence highlights their contribution to the modulation of nociceptive signaling and neuroimmune interactions. Recent studies demonstrate that Mas-related G-protein-coupled receptors are implicated not only in itch transmission but also in the pathophysiology of neuropathic pain, where aberrant receptor activity influences neuronal excitability, glial activation, and inflammatory responses. This review summarizes current knowledge on the molecular mechanisms by which Mas-related G-protein-coupled receptors regulate pain hypersensitivity, including their interactions with ion channels, neuropeptides, and immune mediators. Moreover, the potential of targeting specific Mas-related G-protein-coupled receptor subtypes for therapeutic intervention is discussed, emphasizing their promise as novel druggable candidates for neuropathic pain, the emerging management. Clarifying the roles of Mas-related G-protein-coupled receptors in sensory modulation may provide critical insights into the development of mechanism-based analgesics.

## Full-text entities

- **Genes:** CAMP (cathelicidin antimicrobial peptide) [NCBI Gene 820] {aka CAP-18, CAP18, CRAMP, FALL-39, FALL39, HSD26}, Slc12a5 (solute carrier family 12, member 5) [NCBI Gene 57138] {aka KCC2, mKIAA1176}, Crebbp (CREB binding protein) [NCBI Gene 12914] {aka CBP, CBP/p300, KAT3A, p300/CBP}, Akt1 (Akt serine/threonine kinase 1) [NCBI Gene 11651] {aka Akt, LTR-akt, PKB, PKB/Akt, PKBalpha, Rac}, Nppb (natriuretic peptide type B) [NCBI Gene 18158] {aka BNF, BNP, Iso-ANP}, Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 20848] {aka 1110034C02Rik, Aprf}, Creb1 (cAMP responsive element binding protein 1) [NCBI Gene 12912] {aka 2310001E10Rik, 3526402H21Rik, Creb, Creb-1}, Tslp (thymic stromal lymphopoietin) [NCBI Gene 53603], Rac1 (Rac family small GTPase 1) [NCBI Gene 19353] {aka D5Ertd559e}, Tpsab1 (tryptase alpha/beta 1) [NCBI Gene 100503895] {aka MMCP-7, Mcp-7, Mcp7, Mcpt7}, Hmgb1 (high mobility group box 1) [NCBI Gene 15289] {aka HMG-1, Hmg1, SBP-1, p30}, Napb (N-ethylmaleimide sensitive fusion protein attachment protein beta) [NCBI Gene 17957] {aka Brp14, E161, I47, SNARE, b-SNAP}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, CMA1 (chymase 1) [NCBI Gene 1215] {aka CYH, MCT1, chymase}, Ramp1 (receptor (calcitonin) activity modifying protein 1) [NCBI Gene 51801] {aka 9130218E19Rik}, TAC1 (tachykinin precursor 1) [NCBI Gene 6863] {aka Hs.2563, NK2, NKNA, NPK, TAC2}, Gast (gastrin) [NCBI Gene 14459] {aka GAS}, Trpa1 (transient receptor potential cation channel, subfamily A, member 1) [NCBI Gene 277328] {aka Anktm1, TRPA1b}, Scn11a (sodium channel, voltage-gated, type XI, alpha) [NCBI Gene 24046] {aka NSS2, NaN, NaT, NaV1.9, SNS2}, Calcrl (calcitonin receptor-like) [NCBI Gene 54598] {aka CRLR}, Mrgprb2 (MAS-related GPR, member B2) [NCBI Gene 243979] {aka 4833406I20Rik, Mgrg14}, Mrgpra1 (MAS-related GPR, member A1) [NCBI Gene 233221] {aka MrgA1}, Jun (Jun proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 16476] {aka AP-1, Junc, c-jun}, Rab27b (RAB27B, member RAS oncogene family) [NCBI Gene 80718] {aka 2310021G14Rik, B130064M09Rik}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, Par2 (pulmonary adenoma resistance 2) [NCBI Gene 109447], Bsn (bassoon) [NCBI Gene 12217], Syt12 (synaptotagmin XII) [NCBI Gene 171180], NTS (neurotensin) [NCBI Gene 4922] {aka NMN-125, NN, NT, NT/N, NTS1}, Grm5 (glutamate receptor, metabotropic 5) [NCBI Gene 108071] {aka 6430542K11Rik, Glu5R, Gprc1e, mGluR5, mGluR5b}, PRRT2 (proline rich transmembrane protein 2) [NCBI Gene 112476] {aka BFIC2, BFIS2, DSPB3, DYT10, EKD1, FICCA}, Snap25 (synaptosomal-associated protein 25) [NCBI Gene 20614] {aka Bdr, GENA70, SNAP-25, SUP, sp}, Mrgprd (MAS-related GPR, member D) [NCBI Gene 211578] {aka Gm499, Mgrd, MrgD, TGR7}, Scn10a (sodium channel, voltage-gated, type X, alpha) [NCBI Gene 20264] {aka Nav1.8, PN3, SNS}, TRPA1 (transient receptor potential cation channel subfamily A member 1) [NCBI Gene 8989] {aka ANKTM1, FEPS, FEPS1, p120}, Il33 (interleukin 33) [NCBI Gene 77125] {aka 9230117N10Rik, Il-33, Il1f11, NF-HEV}, Cxcl1 (C-X-C motif chemokine ligand 1) [NCBI Gene 14825] {aka Fsp, Gro1, KC, Mgsa, N51, Scyb1}, Mapk1 (mitogen-activated protein kinase 1) [NCBI Gene 26413] {aka 9030612K14Rik, ERK, Erk2, MAPK2, PRKM2, Prkm1}, Fn1 (fibronectin 1) [NCBI Gene 14268] {aka E330027I09, Fn, Fn-1}, Ptk2 (PTK2 protein tyrosine kinase 2) [NCBI Gene 14083] {aka FADK 1, FAK, FRNK, Fadk, p125FAK}, VIP (vasoactive intestinal peptide) [NCBI Gene 7432] {aka PHM27}, Dlg4 (discs large MAGUK scaffold protein 4) [NCBI Gene 13385] {aka Dlgh4, PSD-95, PSD95, SAP90, SAP90A}, Ntrk1 (neurotrophic tyrosine kinase, receptor, type 1) [NCBI Gene 18211] {aka Tkr, TrkA, trk}, Piezo2 (piezo-type mechanosensitive ion channel component 2) [NCBI Gene 667742] {aka 5930434P17, 9030411M15Rik, 9430028L06Rik, Fam38b, Fam38b2}, Mrgprx2 (MAS-related GPR, member X2) [NCBI Gene 243978] {aka G370024M05Rik, MrgB10, Mrgprb10}, CATHL3 (cathelicidin antimicrobial peptide) [NCBI Gene 281037] {aka BAC7, CAMP, PR-59, PR59}, Ngf (nerve growth factor) [NCBI Gene 18049] {aka Ngfb, beta-NGF}, Bdnf (brain derived neurotrophic factor) [NCBI Gene 12064], Adcy1 (adenylate cyclase 1) [NCBI Gene 432530] {aka AC1, D11Bwg1392e, I-AC, brl}, Mrgpre (MAS-related GPR, member E) [NCBI Gene 244238] {aka C130069N09Rik, Ebrt3, Mgrf, MrgE}, Egr1 (early growth response 1) [NCBI Gene 13653] {aka A530045N19Rik, ETR103, Egr-1, Krox-1, Krox-24, Krox24}, Unc13d (unc-13 homolog D) [NCBI Gene 70450] {aka 2610108D09Rik, Jinx, Munc13-4, mFLJ00067}, Cyp1a2 (cytochrome P450, family 1, subfamily a, polypeptide 2) [NCBI Gene 13077] {aka CP12, CYPIA2, P450-3}, CAMP (cathelicidin antimicrobial peptide) [NCBI Gene 317650] {aka CATHL7}, MRGPRX1 (MAS related GPR family member X1) [NCBI Gene 259249] {aka GPCR, MGRG2, MRGX1, SNSR4}, Pik3r1 (phosphoinositide-3-kinase regulatory subunit 1) [NCBI Gene 18708] {aka PI3K, p50alpha, p55alpha, p85alpha}, Gria1 (glutamate receptor, ionotropic, AMPA1 (alpha 1)) [NCBI Gene 14799] {aka 2900051M01Rik, Glr-1, Glr1, GluA1, GluR-A, GluRA}, Mrgprx3-ps (MAS-related GPR, member X3, pseudogene) [NCBI Gene 100502859] {aka AdeR1, Gm19419, Gm660, Mrgprx3}, Ccl2 (C-C motif chemokine ligand 2) [NCBI Gene 20296] {aka HC11, JE, MCAF, MCP-1, MCP1, SMC-CF}
- **Diseases:** neurogenic inflammation (MESH:D020078), allergic drug reactions (MESH:D004342), CINV (MESH:D020250), irritable bowel syndrome (MESH:D043183), neuronal hyperexcitability (MESH:D009410), prurigo nodularis (MESH:D011536), chronic pain (MESH:D059350), inflammatory bowel disease (MESH:D015212), Neuropathic Pain (MESH:D009437), tissue injury (MESH:D017695), axonal injury (MESH:D001480), neuropathy (MESH:D009422), cognitive impairment (MESH:D003072), multiple sclerosis (MESH:D009103), functional dyspepsia (MESH:D004415), HIV/AIDS (MESH:D015658), atopic dermatitis (MESH:D003876), herpes zoster (MESH:D006562), allodynia (MESH:D006930), viral infections (MESH:D014777), Nerve Injury (MESH:D000080902), angioedema (MESH:D000799), induced neuropathy (MESH:D020269), infections (MESH:D007239), loss of sensory function (MESH:D006315), pruritic (MESH:C535817), respiratory depression (MESH:D012131), urticaria (MESH:D014581), itch (MESH:D011537), metabolic disorders (MESH:D008659), bronchospasm (MESH:D001986), spinal cord injury (MESH:D013119), Pain (MESH:D010146), peripheral nerve injury (MESH:D059348), autoimmune neuropathies (MESH:D020274), inflammation (MESH:D007249), neurodegenerative diseases (MESH:D019636), injury to (MESH:D014947), somatosensory (MESH:D020886), GBS (MESH:D020275), diabetes (MESH:D003920)
- **Chemicals:** lipid (MESH:D008055), endocannabinoid (MESH:D063388), beta-alanine (MESH:D015091), serotonin (MESH:D012701), calcium (MESH:D002118), chloroquine (MESH:D002738), DAG (MESH:D004075), K+ (MESH:D011188), Na+ (MESH:D012964), 3-ethyl-7,8-difluoro-2-isopropylbenzo [4,5]imidazo [1,2-a] pyrimidin-4(1H)-one (-), bile acids (MESH:D001647), fluoroquinolones (MESH:D024841), leukotrienes (MESH:D015289), amino acids (MESH:D000596), vancomycin (MESH:D014640), prostaglandin E2 (MESH:D015232), Aprepitant (MESH:D000077608), IP3 (MESH:D015544), cyclic AMP (MESH:D000242), GDP (MESH:D006153), SLIGRL (MESH:C099570), GTP (MESH:D006160), histamine (MESH:D006632), PIP2 (MESH:D019269), prostaglandins (MESH:D011453)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## References

186 references — full list in the complete paper: https://tomesphere.com/paper/PMC12937618/full.md

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Source: https://tomesphere.com/paper/PMC12937618