Blockade of bradykinin receptors or angiotensin II type 2 receptor prevents paclitaxel-associated acute pain syndrome in mice.
Eur J Pain
; 25(1): 189-198, 2021 01.
Article
en En
| MEDLINE
| ID: mdl-32965065
ABSTRACT
BACKGROUND:
Paclitaxel (PCX) is the first-line choice for the treatment of several types of cancer, including breast, ovarian, and lung cancers. However, patients who receive even a single dose with PCX commonly develop mechanical and cold allodynia, a symptom known as PCX-associated acute pain syndrome (P-APS). Here, we assessed possible involvement of kinin-kallikrein and renin-angiotensin systems in P-APS in mice.METHODS:
Male mice C57Bl/6 wild type (WT) and knockouts for bradykinin receptors, B1 (B1-/- ) and B2 (B2-/- ), were used. Mechanical and cold allodynia were evaluated by using von Frey filaments and acetone test, respectively. P-APS was induced by administration of PCX 4 mg/kg, i.v.. ACE inhibitors (captopril and enalapril), antagonists for angiotensin II type 1 (losartan) and type 2 ([AT2R]; PD123319 and EMA 401) receptors were administrated prior the treatment with PCX. RT-PCR was used to analyse the expression of mRNA for B1, B2 and AT2R receptors.RESULTS:
Administration of PCX in B1-/- and B2-/- mice induced lower mechanical and cold allodynia compared to the WT. However, the pre-treatment with ACE inhibitors reduced the development of mechanical and cold allodynia in P-APS. Surprisingly, we found that mice pre-treatment with the PD123319 or EMA401, but not losartan, prevented the development of mechanical and cold allodynia induced by PCX.CONCLUSION:
Our results demonstrated the involvement of bradykinin receptors B1 and B2 as well as AT2R in the induction of P-APS in mice, and suggest the use of AT2R antagonists as a potential therapy for the prevention of P-APS in humans.SIGNIFICANCE:
Kinin-kallikrein and renin-angiotensin systems, through B1, B2 and AT2 receptors, potentiates paclitaxel-associated acute pain syndrome (P-APS) in mice. Antagonists for AT2R are potential alternatives to prevent P-APS.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Receptores de Bradiquinina
/
Bloqueadores del Receptor Tipo 2 de Angiotensina II
/
Dolor Agudo
/
Antagonistas de los Receptores de Bradiquinina
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Año:
2021
Tipo del documento:
Article