TY - JOUR
T1 - Endothelin ETB receptor antagonist reduces mechanical allodynia in rats with trigeminal neuropathic pain
AU - Chichorro, Juliana Geremias
AU - Zampronio, Aleksander Roberto
AU - Rae, Giles Alexander
PY - 2006/6
Y1 - 2006/6
N2 - Trigeminal neuropathic pain, which is associated with marked orofacial mechanical allodynia, is frequently refractory to currently available drugs. Because endothelins (ETs) can contribute to nociceptive changes in animal models of inflammatory, cancer, and diabetic neuropathic pain, the present study evaluated the influence of ETA and ETB receptor antagonists on orofacial mechanical allodynia in a rat model of trigeminal neuropathic pain. Unilateral constriction (C) of the infraorbital nerve (ION) caused pronounced and sustained bilateral mechanical allodynia, evaluated by application of von Frey hairs to the vibrissal pad. Mechanical allodynia on postoperative days 12-15 after nerve injury was abolished for up to 90 mins by subcutaneous administration of 2.5 mg/kg morphine, but was fully refractory to intravenous (iv) administration of 10 mg/kg of the dual ETA plus ETB or selective ETA receptor antagonists, bosentan and atrasentan, respectively. In sharp contrast, iv administration of 20 mg/kg of the selective ETB receptor antagonist, A-192621, caused a net 61 ± 15% reduction of mechanical threshold, lasting 2 hrs. Co-injection of atrasentan plus A-192621 did not modify ION injury-induced mechanical allodynia. Injection of 10 pmol ET-1 into the upper lip of naive rats caused ipsilateral mechanical allodynia lasting up to 5 hrs. Thus, ETB receptor-mediated mechanisms contribute to orofacial mechanical allodynia induced by CION injury, but, somehow, functional ETA receptors are required for expression of the antiallodynic effect of ETB receptor blockade.
AB - Trigeminal neuropathic pain, which is associated with marked orofacial mechanical allodynia, is frequently refractory to currently available drugs. Because endothelins (ETs) can contribute to nociceptive changes in animal models of inflammatory, cancer, and diabetic neuropathic pain, the present study evaluated the influence of ETA and ETB receptor antagonists on orofacial mechanical allodynia in a rat model of trigeminal neuropathic pain. Unilateral constriction (C) of the infraorbital nerve (ION) caused pronounced and sustained bilateral mechanical allodynia, evaluated by application of von Frey hairs to the vibrissal pad. Mechanical allodynia on postoperative days 12-15 after nerve injury was abolished for up to 90 mins by subcutaneous administration of 2.5 mg/kg morphine, but was fully refractory to intravenous (iv) administration of 10 mg/kg of the dual ETA plus ETB or selective ETA receptor antagonists, bosentan and atrasentan, respectively. In sharp contrast, iv administration of 20 mg/kg of the selective ETB receptor antagonist, A-192621, caused a net 61 ± 15% reduction of mechanical threshold, lasting 2 hrs. Co-injection of atrasentan plus A-192621 did not modify ION injury-induced mechanical allodynia. Injection of 10 pmol ET-1 into the upper lip of naive rats caused ipsilateral mechanical allodynia lasting up to 5 hrs. Thus, ETB receptor-mediated mechanisms contribute to orofacial mechanical allodynia induced by CION injury, but, somehow, functional ETA receptors are required for expression of the antiallodynic effect of ETB receptor blockade.
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M3 - Article
C2 - 16741064
AN - SCOPUS:33744903641
SN - 1535-3702
VL - 231
SP - 1136
EP - 1140
JO - Experimental Biology and Medicine
JF - Experimental Biology and Medicine
IS - 6
ER -