Table 2.
Potential neural pathways and mechanisms of pruritus
| Nerve subtypes | Peripheral activating ligands | Neural receptors |
|---|---|---|
| CMi: C-fibres, unmyelinated, insensitive to mechanical stimulation |
Histamine | H1R |
| Capsaicin and other vanilloids Endocannabinoids? |
TRPV1 | |
| CMH: C-fibres, unmyelinated, mechanical and heat sensitive |
Tryptase | PAR2 |
| Cowhage mucunain protease | (PAR4) | |
| Vespid, dust mite, and other proteases? | TRPV1 | |
| Stinging nettles and other plant toxins | ||
| Capsaicin and other vanilloids | ||
| Heat | ||
| Endocannabinoids? | ||
| C-fibres: mechanical and heat insensitive | Proteases | PAR2/4 |
| C-fibres: not further differentiated | Histamine | H4R? |
| Other endogenous ligands? | ||
| C-fibres: not further differentiated | GRP and related peptides, such as neuromedin B and bombesin |
GRPR |
| C-fibres: not further differentiated | CGRP | CGRP R1, R2, or related receptors |
| Substance P/neurokinin A | NK1, NK2 | |
| C-fibres: not further differentiated | ATP | MRGRP subtypes |
| Chloroquine | ||
| BAM8–22 | TRPA1 | |
| Opioid peptides (γ2-melanocyte-stimulating hormone |
||
| C-fibres: not further differentiated | Interleukin-31 | Interleukin-31 receptor A—oncostatin M heterodimer |
| Aδ fibres? | – | – |
| ? | ? | Heterohexameric TRP protein sensors |
ATP adenosine triphosphate; CGRP calcitonin gene-related peptide; CMH type C mechanical plus heat nociceptors; CMi C mechano-insensitive nerve fibre; GPR G protein–coupled receptor; GRP gastrin-releasing peptide; GRPR GRP receptor; H1R histamine receptor 1; H4R histamine receptor 4; MRGRP MAS-related GPR member P; NK1 neurokinin receptor 1; NK2 neurokinin receptor 2; PAR protease-activated receptor; TRP transient receptor potential; TRPA1 TRP ankyrin 1; TRPV1, TRP vanilloid 1