Xian-Yu Liu<\/strong>1<\/a><\/sup>2<\/a><\/sup>,\u00a0<\/span>Li Wan<\/strong>1<\/a><\/sup>2<\/a><\/sup>,\u00a0<\/span>Fu-Quan Huo<\/strong>1<\/a><\/sup>2<\/a><\/sup>,\u00a0<\/span>Devin M Barry<\/strong>1<\/a><\/sup>2<\/a><\/sup>,\u00a0<\/span>Hui Li<\/strong>1<\/a><\/sup>2<\/a><\/sup>,\u00a0<\/span>Zhong-Qiu Zhao<\/strong>1<\/a><\/sup>2<\/a><\/sup>and\u00a0<\/span>Zhou-Feng Chen<\/strong>1<\/a><\/sup>2<\/a><\/sup>3<\/a><\/sup>4<\/a><\/sup><\/p>\n A recent study by Mishra and Hoon identified B-type natriuretic peptide (BNP) as an important peptide for itch transmission and proposed that BNP activates spinal natriuretic peptide receptor-A (NPRA) expressing neurons, which release gastrin releasing peptide (GRP) to activate GRP receptor (GRPR) expressing neurons to relay itch information from the periphery to the brain (Science<\/em>340:968\u2013971, 2013). A central premise for the validity of this novel pathway is the absence of GRP in the dorsal root ganglion (DRG) neurons. To this end, they showed that\u00a0Grp<\/em>\u00a0mRNA in DRG neurons is either absent or barely detectable and claimed that BNP but not GRP is a major neurotransmitter for itch in pruriceptors. They showed that NPRA immunostaining is perfectly co-localized with\u00a0Grp<\/em>-eGFP in the spinal cord, and a few acute pain behaviors in\u00a0Nppb<\/em>-\/-<\/em><\/sup>\u00a0mice were tested. They claimed that BNP is an itch-selective peptide that acts as the first station of a dedicated neuronal pathway comprising a GRP-GRPR cascade for itch. However, our studies, along with the others, do not support their claims.<\/p>\n We were unable to reproduce the immunostaining of BNP and NPRA as shown by Mishra and Hoon. By contrast, we were able to detect\u00a0Grp<\/em>\u00a0mRNA in DRGs using\u00a0in situ<\/em>\u00a0hybridization and real time RT-PCR. We show that the expression pattern of\u00a0Grp<\/em>\u00a0mRNA is comparable to that of GRP protein in DRGs. Pharmacological and genetic blockade of GRP-GRPR signaling does not significantly affect intrathecal BNP-induced scratching behavior. We show that BNP inhibits inflammatory pain and morphine analgesia.<\/p>\n Accumulating evidence demonstrates that GRP is a key neurotransmitter in pruriceptors for mediating histamine-independent itch. BNP-NPRA signaling is involved in both itch and pain and does not function upstream of the GRP-GRPR dedicated neuronal pathway. The site of BNP action in itch and pain and its relationship with GRP remain to be clarified.<\/p>\n<\/div>\n<\/section>\nAbstract<\/h3>\n
Background<\/h4>\n
Findings<\/h4>\n
Conclusions<\/h4>\n
Keywords:<\/h5>\n