Pain persists in mice lacking both Substance P and CGRPα signaling
- National Center for Complementary and Integrative Health, National Institutes of Health, United States
- National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States
Figures
Figure 1 with 1 supplement
Tac1::Calca DKO mice lack Substance P and CGRPα peptides throughout the nervous system.
(A) Confocal images showing Substance P immunostaining in the dorsal root ganglion (DRG), spinal cord dorsal horn and midbrain of a WT mouse (top). No staining is detectable in the DKO (bottom). (B) …
Figure 1—figure supplement 1
Substance P-sniffer cells selectively respond to Substance P.
(A) Dose-response curve showing Substance P activates Substance P-sniffer cells at low nanomolar concentrations (EC50=11.8 nM), but cells are insensitive to CGRPα. (B) Dose-response curve showing …
Figure 2 with 2 supplements
Tac1::Calca DKO mice respond to acute painful and itching stimuli.
(A) 50% withdrawal threshold for von Frey punctate stimulation (log g). n=14 (7M, 7 F) for WT & n=14 (7M, 7 F) for DKO. (B) Percentage response to noxious pinprick stimulation. n=13 (5M, 8 F) for WT …
Figure 2—figure supplement 1
Tac1::Calca DKO mice develop LiCl-induced conditioned taste aversion.
(A) Quantification of conditioned taste aversion (CTA) test in WT (blue) and DKO (red) mice. Saccharin preference index on test day is shown for animals given either lithium chloride or PBS …
Figure 2—figure supplement 2
Capsaicin evokes Fos activity in the dorsal horn of Tac1::Calca DKO mice.
(A) Example confocal images showing dorsal horn of WT and DKO mice backlabelled with CTB (magenta) from the paw. Similar numbers of Fos puncta (green) are visible in the ipsilateral superficial …
Figure 3
Tac1::Calca DKO mice display inflammatory pain and neurogenic inflammation.
(A) Time course of the change in the Hargreaves’ radiant heat withdrawal latencies of the hindpaw of WT and DKO mice following intraplantar injection of Complete Freund’s Adjuvant (CFA). n=10 (5M, 5 …
Figure 4
Tac1::Calca DKO mice develop neuropathic pain associated with nerve injury and the chemotherapeutic drug oxaliplatin.
(A) Time course of the change in the von Frey 50% withdrawal threshold (log g) of the hindpaw of WT and DKO mice after sciatic spared nerve injury. n=8 (4M, 4 F) for WT and n=8 (4M, 4 F) for DKO. (B)…
Additional files
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Supplementary file 1
Table summarizing all statistical tests used in the manuscript.
- https://cdn.elifesciences.org/articles/93754/elife-93754-supp1-v1.docx
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MDAR checklist
- https://cdn.elifesciences.org/articles/93754/elife-93754-mdarchecklist1-v1.docx
