Gastrin-Releasing Peptide-Expressing Nerves Comprise Subsets of Human Cutaneous Aδ and C Fibers that May Sense Pruritus

Loss of Papillary Dermal Calcitonin Gene Related Peptide-Expressing Neurons Significantly Correlates with Uremic Pruritus

“…In ESRD control subjects, of total papillary dermal (PD)-protein gene product 9.5 þ nerves, CGRP-expressing nerves accounted for approximately 28% (% PD-CGRP þ ), NPPB-expressing nerves approximate 1.8% (%PD-NPPB þ ), and SP-expressing nerves approximately 3% (%PD-SP þ ). This %PD-CGRP þ was similar to that measured of back (w26%) and trunk (w21%) in normal human skin without pruritus or skin disease (Timmes et al, 2013) (see Supplementary Tables S4 and S5 online). %PD-CGRP þ was significantly reduced by approximately 81% in UPS (P < 0.0001), with the absolute loss of PD-CGRP þ nerves (median, ¼ w670 mm/mm epidermis) similar to the absolute decrease in PDNL/mm (median ¼ w711 mm/mm epidermis).…”

“…Quantitation of TRPV-1 antibody staining showed no significant difference between UPS and controls for intraepidermal nerve fiber density (P ¼ 0.1) or epidermal nerve length in mm/mm of epidermis (P ¼ 0.31) ( Table 1). In all ESRD subjects, CGRP-, SP-, or NPPBexpressing intraepidermal nerves were virtually absent (see Supplementary Figures S1eS3), as were intraepidermal CGRP þ and SP þ nerves in normal human skin (Timmes et al, 2013).…”

“…To our knowledge, quantitative neuroanatomic changes in putative itch-and/or painsensing innervation in UP skin have not been reported to date. Human cutaneous pain-and/or itch-sensing nerves include peptidergic Ad-and C-fibers that terminate at or near the dermal-epidermal junction and express TRPV-1, calcitonin gene related peptide (CGRP), and substance P (SP) (Timmes et al, 2013). In rodent skin, itch specificity may further be conferred by expression of natriuretic polypeptide b (NPPB) (Mishra and Hoon, 2013).…”

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…Indeed, TRPV1-expressing pruriceptive afferents contain gastrin-releasing peptide (GRP) in humans (Timmes et al, 2013). Mice whose GRP receptors have been deleted by genetic manipulation were reported to show normal pain response but no scratching (itch) behavior (Sun and Chen, 2007).…”

Immediate‐type allergic and protease‐mediated reactions are involved in scratching behaviour induced by topical application of Dermatophagoides farinae extract in NC/Nga mice

“…Previous studies have demonstrated that intra‐dermal injection of GRP was found to elicit scratching behaviour in mice, at least partly, through activation of BB 2 bombesin receptors present in the mast cells, triggering their degradation . Recently, GRP‐expressing nerve fibres were found in human skin and the majority of the nerve fibres coexpressed SP . These findings suggest that GRP released from the peripheral terminals of primary sensory neurons also increases scratching behaviour in the early phase.…”