Anti-Allodynic Effect of Intracerebroventricularly Administered Antioxidant and Free Radical Scavenger in a Mouse Model of Orofacial Pain

Aims: To evaluate possible effects of the intracerebroventricular (icv) injection of either O-Tricyclo [5.2.1.02,6] dec-9-yl dithiocarbonate potassium salt (D609), a potent antioxidant and inhibitor of phosphatidylcholine specific phospholipase C (PtdCho-PLC) and acid sphingomyelinase (ASMase), or the spin trap/free radical scavenger N-tert-Butyl-a-phenylnitrone (PBN), on mechanical allodynia induced by facial carrageenan injection in mice. Methods: Balb/c mice received icv injection of D609/PBN plus facial carrageenan injection, and the number of face wash strokes to von Frey hair mechanical stimulation of the maxillary skin was quantified. PtdCho-PLC and ASMase activities were also assayed in the brainstem, thalamus, and somatosensory cortex. Results: Mice that received the icv injection of 10 nmol D609 plus facial carrageenan injection showed significantly fewer face wash strokes evoked by von Frey hair stimulation (indicating reduced mechanical allodynia) at 1 and 3 days post-injection, compared to mice that received icv injection of isotonic saline plus facial carrageenan injection. Mice that received icv injection of 1.13 µmol PBN plus facial carrageenan injection likewise showed significantly fewer face wash strokes after facial carrageenan injection, compared to isotonic saline-injected plus carrageenan-injected controls. D609 injection also resulted in significantly reduced ASMase activity in the brainstem, thalamus, and somatosensory cortex 3 days after injection, compared to controls. Conclusion: The icv injections of D609 and PBN were effective in reducing mechanical allodynia after facial carrageenan injection-induced pain. Together, the results point to a possible role of central nervous system sphingolipids and/or free radicals in orofacial pain. Palabras clave: acid sphingomyelinase, free radicals, mechanical allodynia, orofacial pain, phosphatidylcholine specific phospholipase C, reactive oxygen species, ROS