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Spinal activation of the NPY Y1 receptor reduces mechanical and cold allodynia in rats with chronic constriction injury.
Peptides. 2017 06; 92:38-45.P

Abstract

Neuropeptide tyrosine (NPY) and its associated receptors Y1R and Y2R have been previously implicated in the spinal modulation of neuropathic pain induced by total or partial sectioning of the sciatic nerve. However, their role in chronic constrictive injuries of the sciatic nerve has not yet been described. In the present study, we analyzed the consequences of pharmacological activation of spinal Y1R, by using the specific Y1R agonist Leu31Pro34-NPY, in rats with chronic constriction injury (CCI). CCI and sham-injury rats were implanted with a permanent intrathecal catheter (at day 7 after injury), and their response to the administration of different doses (2.5, 5, 7, 10 or 20μg) of Leu31Pro34-NPY (at a volume of 10μl) through the implanted catheter, recorded 14days after injury. Mechanical allodynia was tested by means of the up-and-down method, using von Frey filaments. Cold allodynia was tested by application of an acetone drop to the affected hindpaw. Intrathecal Leu31Pro34-NPY induced an increase of mechanical thresholds in rats with CCI, starting at doses of 5μg and becoming stronger with higher doses. Intrathecal Leu31Pro34 also resulted in reductions in the frequency of withdrawal to cold stimuli, although the effect was somewhat more moderate and mostly observed for doses of 7μg and higher. We thus show that spinal activation of the Y1R is able to reduce neuropathic pain due to a chronic constrictive injury and, together with other studies, support the use of a spinal Y1R agonist as a therapeutic agent against chronic pain induced by peripheral neuropathy.

Authors+Show Affiliations

Instituto de Investigaciones en Medicina Traslacional (IIMT), Consejo Nacional de Investigaciones Cientiíficas y Técnicas (CONICET) - Austral University, Avenida Juan D. Perón 1500, B1629AHJ, Pilar, Buenos Aires, Argentina.Instituto de Investigaciones en Medicina Traslacional (IIMT), Consejo Nacional de Investigaciones Cientiíficas y Técnicas (CONICET) - Austral University, Avenida Juan D. Perón 1500, B1629AHJ, Pilar, Buenos Aires, Argentina.Instituto de Investigaciones en Medicina Traslacional (IIMT), Consejo Nacional de Investigaciones Cientiíficas y Técnicas (CONICET) - Austral University, Avenida Juan D. Perón 1500, B1629AHJ, Pilar, Buenos Aires, Argentina.Instituto de Investigaciones en Medicina Traslacional (IIMT), Consejo Nacional de Investigaciones Cientiíficas y Técnicas (CONICET) - Austral University, Avenida Juan D. Perón 1500, B1629AHJ, Pilar, Buenos Aires, Argentina.Instituto de Investigaciones en Medicina Traslacional (IIMT), Consejo Nacional de Investigaciones Cientiíficas y Técnicas (CONICET) - Austral University, Avenida Juan D. Perón 1500, B1629AHJ, Pilar, Buenos Aires, Argentina. Electronic address: pbrumovs@austral.edu.ar.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28465077

Citation

Malet, Mariana, et al. "Spinal Activation of the NPY Y1 Receptor Reduces Mechanical and Cold Allodynia in Rats With Chronic Constriction Injury." Peptides, vol. 92, 2017, pp. 38-45.
Malet M, Leiguarda C, Gastón G, et al. Spinal activation of the NPY Y1 receptor reduces mechanical and cold allodynia in rats with chronic constriction injury. Peptides. 2017;92:38-45.
Malet, M., Leiguarda, C., Gastón, G., McCarthy, C., & Brumovsky, P. (2017). Spinal activation of the NPY Y1 receptor reduces mechanical and cold allodynia in rats with chronic constriction injury. Peptides, 92, 38-45. https://doi.org/10.1016/j.peptides.2017.04.005
Malet M, et al. Spinal Activation of the NPY Y1 Receptor Reduces Mechanical and Cold Allodynia in Rats With Chronic Constriction Injury. Peptides. 2017;92:38-45. PubMed PMID: 28465077.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Spinal activation of the NPY Y1 receptor reduces mechanical and cold allodynia in rats with chronic constriction injury. AU - Malet,Mariana, AU - Leiguarda,Candelaria, AU - Gastón,Guillermo, AU - McCarthy,Carly, AU - Brumovsky,Pablo, Y1 - 2017/04/29/ PY - 2017/01/18/received PY - 2017/03/29/revised PY - 2017/04/19/accepted PY - 2017/5/4/pubmed PY - 2018/2/22/medline PY - 2017/5/4/entrez KW - Allodynia KW - Inhibition KW - Neuropathic pain KW - Neuropeptides KW - Sciatic nerve KW - Spinal cord SP - 38 EP - 45 JF - Peptides JO - Peptides VL - 92 N2 - Neuropeptide tyrosine (NPY) and its associated receptors Y1R and Y2R have been previously implicated in the spinal modulation of neuropathic pain induced by total or partial sectioning of the sciatic nerve. However, their role in chronic constrictive injuries of the sciatic nerve has not yet been described. In the present study, we analyzed the consequences of pharmacological activation of spinal Y1R, by using the specific Y1R agonist Leu31Pro34-NPY, in rats with chronic constriction injury (CCI). CCI and sham-injury rats were implanted with a permanent intrathecal catheter (at day 7 after injury), and their response to the administration of different doses (2.5, 5, 7, 10 or 20μg) of Leu31Pro34-NPY (at a volume of 10μl) through the implanted catheter, recorded 14days after injury. Mechanical allodynia was tested by means of the up-and-down method, using von Frey filaments. Cold allodynia was tested by application of an acetone drop to the affected hindpaw. Intrathecal Leu31Pro34-NPY induced an increase of mechanical thresholds in rats with CCI, starting at doses of 5μg and becoming stronger with higher doses. Intrathecal Leu31Pro34 also resulted in reductions in the frequency of withdrawal to cold stimuli, although the effect was somewhat more moderate and mostly observed for doses of 7μg and higher. We thus show that spinal activation of the Y1R is able to reduce neuropathic pain due to a chronic constrictive injury and, together with other studies, support the use of a spinal Y1R agonist as a therapeutic agent against chronic pain induced by peripheral neuropathy. SN - 1873-5169 UR - https://www.unboundmedicine.com/medline/citation/28465077/Spinal_activation_of_the_NPY_Y1_receptor_reduces_mechanical_and_cold_allodynia_in_rats_with_chronic_constriction_injury_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0196-9781(17)30175-4 DB - PRIME DP - Unbound Medicine ER -