Table 1.
Physiology of Pruritoceptive Itch
| Pruritogens | Origin | Receptors & Mediators | Clinical Applicability | |
|---|---|---|---|---|
| Peripheral | Histamine | Mast cells | H1 & H4, TRPV1 | H1 & H4 antagonists show benefit in reducing pruritus both in chronic itch and in patients with atopic dermatitis [20–22] |
| Tryptase | Mast cells | PAR2, PAR4 [3], TRPV1, BNP | PAR2 upregulated in atopic dermatitis [23] & causes an itch without wheal [24]; PAR2 antagonists could combat chronic nonhistaminic itch [25]; removal of TRPV1 ion channel and BNP from neurons suppressed itch in mice [26] | |
| Mucunain | Cowhage | |||
| Dust mites | Mites | |||
| Capsaicin | Chili | TRPV1 [1] | Topical capsaicin reduced itch in chronic psoriasis [27], uremic patients [28], and hemodialysis attenders [29]; the capsaicin 8% patch has also shown success in addressing neurogenic itch such as brachioradial pruritus and meralgia paresthetica [30] | |
| Endothelin 1 | Endothelium | ET(A), ET(B) [31] | Upregulated in chronic itch patients [31] | |
| Cytokines | TH2 cells | IL-31, IL-31RA, OSMR [32] | IL-31 induces itch in mice [33]; anti-IL-31 shown to reduce itch in atopic dermatitis patients [34] | |
| Kallikrein 5 | Epithelium | PAR2 [35] | Increased scratching in mice with increased kallikrein 5 expression [35,36] | |
| Substance P | Afferent neurons | NK1 [37] | Substance P levels involved in atopic dermatitis pathophysiology [38,39]; TRPV1 agonists shown to deplete substance P levels peripherally [1]; substance P elevated in prurigo nodularis patients [40] | |
| Central | Opioids | Exogenous neurons & keratinocytes | μ- & κ-receptors | Morphine induces scratching and μ-opioid antagonist shown to relieve chronic itch [41] |
| 5-HT | 5-HT | TRPV1 | Involved in polycythemia vera & cholestasis itch [42]; more pruritogenic than histamine in rats [43]; serotonin injection induces pruritus in healthy patients [44]; SSRIs shown to reduce chronic itch [45]; ondansetron effective in cholestatic itch [46] |
5-HT = serotonin; BNP= type b natriuretic polypeptide; ET = endothelin; IL-31RA = interleukin-31 receptor A; NK1 = neurokinin 1; OSMR = oncostatin M receptor; PAR= protease activated receptors; SSRI = selective serotonin reuptake inhibitor; TRPV1 = transient receptor potential villanoid 1.