Endothelin-1 (ET-1) predominates in the
endothelin family effectively in vascular tone control, mitogenesis, and neuromodulation. Its receptors are widespread in the central nervous system (CNS) associated with endogenous
pain control, suggesting an important role of ET-1 in central
pain processing. This study aimed to evaluate the effect of central ET-1 on the development of
neuropathic pain behaviour by repeated intrathecal administration of
endothelin type A receptor (ETAR) antagonist (BQ-123) in a sciatic nerve
ligation (SNL) animal model.
BQ-123 was administered intrathecally to rats at dosages 15 μg, 20 μg, 25 μg, and 30 μg, daily for 3 days.
Mechanical allodynia was assessed daily 30 minutes before/after injection, 1 hour after injection of
BQ-123 from post-SNL day 4 to day 6, and once on day 7 (without
BQ-123 administration) before rats were sacrificed. Increasing trends of mechanical threshold were observed, and they reached significance at all dosages on post-SNL day 7 (P < 0.05 at dosage 15 μg and P < 0.001 at dosages 20 μg, 25 μg, and 30 μg) in comparison to control group.
BQ-123 at dosage 30 μg showed the most stable and significant mechanical threshold rise. Repeated central administration of
BQ-123 alleviated
mechanical allodynia after SNL. Our results provide insight into the therapeutic strategies, including timing, against
neuropathic pain development with ETAR antagonist.