TY - JOUR
T1 - NTS1 and NTS2 mediate analgesia following neurotensin analog treatment in a mouse model for visceral pain
AU - Smith, Kristin E.
AU - Boules, Mona
AU - Williams, Katrina
AU - Richelson, Elliott
N1 - Funding Information:
This work was supported by the Siragusa Foundation Career Development Award (M. Boules), as well as the Mayo Foundation for Medical Education and Research. We acknowledge Hannah Johnston, Jessica Tozy, Lorissa Lameroux, Eileen Beatrice, and Joshua Reed for their help with the writhing assays.
PY - 2012/6/15
Y1 - 2012/6/15
N2 - Neurotensin (NT) analogs, NT69L, NT72, and NT79, differentially bind the two major neurotensin receptors, NTS1 and NTS2, to elicit effects similar to those of endogenous NT, including analgesia. Previous data strongly suggest NTS2 as the main receptor involved in NT- and NT analog-mediated visceral analgesia. However, this idea has yet to be confirmed with the use of mice lacking the NTS2 receptor. Here we use the writhing assay, a model of visceral pain, to investigate the analgesic effects of NT69L (binds NTS1 and NTS2 equally), NT79 (NTS2-selective), NT72 (NTS1 selective) and levocabastine (NTS2-selective) in WT, NTS1 knock-out, and NTS2 knock-out mice. Additionally, we investigate the role of NTS2 in the development of tolerance to NT69L-mediated visceral analgesia. All three NT analogs reduced writhing in the WT mice. NT79 and levocabsatine reduced writhing in the NTS1 -/- mice while NT69L and NT72 showed significant analgesic effect in the NTS2 -/- mice. In conclusion, the data shows that (1) both NTS1 and NTS2 are involved in mediating visceral analgesia and their respective roles appear to be NT analog-dependent; (2) NTS1 may inhibit NTS2-mediated analgesia; and (3) NTS2 is necessary for the development of tolerance to NT69L-mediated analgesia.
AB - Neurotensin (NT) analogs, NT69L, NT72, and NT79, differentially bind the two major neurotensin receptors, NTS1 and NTS2, to elicit effects similar to those of endogenous NT, including analgesia. Previous data strongly suggest NTS2 as the main receptor involved in NT- and NT analog-mediated visceral analgesia. However, this idea has yet to be confirmed with the use of mice lacking the NTS2 receptor. Here we use the writhing assay, a model of visceral pain, to investigate the analgesic effects of NT69L (binds NTS1 and NTS2 equally), NT79 (NTS2-selective), NT72 (NTS1 selective) and levocabastine (NTS2-selective) in WT, NTS1 knock-out, and NTS2 knock-out mice. Additionally, we investigate the role of NTS2 in the development of tolerance to NT69L-mediated visceral analgesia. All three NT analogs reduced writhing in the WT mice. NT79 and levocabsatine reduced writhing in the NTS1 -/- mice while NT69L and NT72 showed significant analgesic effect in the NTS2 -/- mice. In conclusion, the data shows that (1) both NTS1 and NTS2 are involved in mediating visceral analgesia and their respective roles appear to be NT analog-dependent; (2) NTS1 may inhibit NTS2-mediated analgesia; and (3) NTS2 is necessary for the development of tolerance to NT69L-mediated analgesia.
KW - Analgesia
KW - NT69L
KW - NT72
KW - NT79
KW - Tolerance
KW - Writhing
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U2 - 10.1016/j.bbr.2012.03.044
DO - 10.1016/j.bbr.2012.03.044
M3 - Article
C2 - 22504145
AN - SCOPUS:84859929441
SN - 0166-4328
VL - 232
SP - 93
EP - 97
JO - Behavioural Brain Research
JF - Behavioural Brain Research
IS - 1
ER -