Abstract
Recent studies support roles for neurokinin-1 (NK-1) and gastrin-releasing peptide (GRP) receptor-expressing spinal neurons in itch. We presently investigated expression of substance P (SP) and GRP in pruritogen-responsive primary sensory neurons and roles for these neuropeptides in itch signaling. Responses of dorsal root ganglion (DRG) cells to various pruritogens were observed by calcium imaging. DRG cells were then processed for SP, GRP, and isolectin B-4 (IB4; a marker for nonpeptidergic neurons) immunofluorescence. Of prurito-gen-responsive DRG cells, 11.8 -26.8%, 21.8-40.0%, and 21.4-26.8% were immunopositive for SP, GRP, and IB4, respectively. In behavioral studies, both systemic and intrathecal administration of a NK-1 receptor antagonist significantly attenuated scratching evoked by chloroquine and a protease-activated receptor 2 agonist, SLIGRL, but not histamine, bovine adrenal medulla peptide 8-22 (BAM8-22), or serotonin. Systemic or intrathecal administration of a GRP receptor antagonist attenuated scratching evoked by chloroquine and SLIGRL but not BAM8-22 or histamine. The GRP receptor antagonist enhanced scratching evoked by serotonin. These results indicate that SP and GRP expressed in primary sensory neurons are partially involved as neurotransmitters in histamine-independent itch signaling from the skin to the spinal cord.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 742-748 |
| Number of pages | 7 |
| Journal | Journal of Neurophysiology |
| Volume | 109 |
| Issue number | 3 |
| DOIs | |
| State | Published - 2013 |
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Keywords
- Dorsal root ganglion cell
- Itch
- Mouse
- Scratching
ASJC Scopus subject areas
- Physiology
- Neuroscience(all)
Cite this
Roles for substance P and gastrin-releasing peptide as neurotransmitters released by primary afferent pruriceptors. / Akiyama, Tasuku; Tominaga, Mitsutoshi; Davoodi, Auva; Nagamine, Masaki; Blansit, Kevin; Horwitz, Alexander; Carstens, Mirela Iodi; Carstens, Earl.
In: Journal of Neurophysiology, Vol. 109, No. 3, 2013, p. 742-748.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Roles for substance P and gastrin-releasing peptide as neurotransmitters released by primary afferent pruriceptors
AU - Akiyama, Tasuku
AU - Tominaga, Mitsutoshi
AU - Davoodi, Auva
AU - Nagamine, Masaki
AU - Blansit, Kevin
AU - Horwitz, Alexander
AU - Carstens, Mirela Iodi
AU - Carstens, Earl
PY - 2013
Y1 - 2013
N2 - Recent studies support roles for neurokinin-1 (NK-1) and gastrin-releasing peptide (GRP) receptor-expressing spinal neurons in itch. We presently investigated expression of substance P (SP) and GRP in pruritogen-responsive primary sensory neurons and roles for these neuropeptides in itch signaling. Responses of dorsal root ganglion (DRG) cells to various pruritogens were observed by calcium imaging. DRG cells were then processed for SP, GRP, and isolectin B-4 (IB4; a marker for nonpeptidergic neurons) immunofluorescence. Of prurito-gen-responsive DRG cells, 11.8 -26.8%, 21.8-40.0%, and 21.4-26.8% were immunopositive for SP, GRP, and IB4, respectively. In behavioral studies, both systemic and intrathecal administration of a NK-1 receptor antagonist significantly attenuated scratching evoked by chloroquine and a protease-activated receptor 2 agonist, SLIGRL, but not histamine, bovine adrenal medulla peptide 8-22 (BAM8-22), or serotonin. Systemic or intrathecal administration of a GRP receptor antagonist attenuated scratching evoked by chloroquine and SLIGRL but not BAM8-22 or histamine. The GRP receptor antagonist enhanced scratching evoked by serotonin. These results indicate that SP and GRP expressed in primary sensory neurons are partially involved as neurotransmitters in histamine-independent itch signaling from the skin to the spinal cord.
AB - Recent studies support roles for neurokinin-1 (NK-1) and gastrin-releasing peptide (GRP) receptor-expressing spinal neurons in itch. We presently investigated expression of substance P (SP) and GRP in pruritogen-responsive primary sensory neurons and roles for these neuropeptides in itch signaling. Responses of dorsal root ganglion (DRG) cells to various pruritogens were observed by calcium imaging. DRG cells were then processed for SP, GRP, and isolectin B-4 (IB4; a marker for nonpeptidergic neurons) immunofluorescence. Of prurito-gen-responsive DRG cells, 11.8 -26.8%, 21.8-40.0%, and 21.4-26.8% were immunopositive for SP, GRP, and IB4, respectively. In behavioral studies, both systemic and intrathecal administration of a NK-1 receptor antagonist significantly attenuated scratching evoked by chloroquine and a protease-activated receptor 2 agonist, SLIGRL, but not histamine, bovine adrenal medulla peptide 8-22 (BAM8-22), or serotonin. Systemic or intrathecal administration of a GRP receptor antagonist attenuated scratching evoked by chloroquine and SLIGRL but not BAM8-22 or histamine. The GRP receptor antagonist enhanced scratching evoked by serotonin. These results indicate that SP and GRP expressed in primary sensory neurons are partially involved as neurotransmitters in histamine-independent itch signaling from the skin to the spinal cord.
KW - Dorsal root ganglion cell
KW - Itch
KW - Mouse
KW - Scratching
UR - http://www.scopus.com/inward/record.url?scp=84873326725&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84873326725&partnerID=8YFLogxK
U2 - 10.1152/jn.00539.2012
DO - 10.1152/jn.00539.2012
M3 - Article
C2 - 23155177
AN - SCOPUS:84873326725
VL - 109
SP - 742
EP - 748
JO - Journal of Neurophysiology
JF - Journal of Neurophysiology
SN - 0022-3077
IS - 3
ER -