title: Lack of the nitric oxide-cyclic GMP-potassium channel pathway for the antinociceptive effect of intrathecal zaprinast in a rat formalin test.
abstract: Zaprinast is a phosphodiesterase inhibitor that is active in various models of pain when administered locally. In addition, the antinociception of zaprinast is involved in the nitric oxide (NO)-cGMP pathway. However, the effect of zaprinast administered spinally has not been examined. Therefore, this study examined the effect of zaprinast on the formalin-induced nociception at the spinal level. Next, the role of the NO-cGMP-potassium channel pathway on the effect of zaprinast was further clarified. Catheters were inserted into the intrathecal space of male Sprague-Dawley (SD) rats. Pain was induced by applying 50 microl of a 5% formalin solution to the hindpaw. The change in the zaprinast-induced effect was examined after an intrathecal pretreatment with a NO synthase inhibitor (l-NMMA), a guanylyl cyclase inhibitor (ODQ) or a potassium channel blocker (glibenclamide). Zaprinast produced an antinociceptive effect during phase 1 and phase 2 in the formalin test. Intrathecal l-NMMA, ODQ and glibenclamide did not reverse the antinociception of zaprinast in either phase of the formalin test. These results suggest that zaprinast is effective against both acute pain and the facilitated pain state at the spinal level. However, the NO-sensitive cGMP-potassium channel pathway is not contributable to the antinociceptive mechanism of zaprinast in the spinal cord.
authors.affiliation: Department of Anesthesiology and Pain Medicine, Chonnam National University, Medical School, 8 Hakdong, Dongku, Gwangju 501-757, Republic of Korea. mhyoon@chonnam.ac.kr
authors.forename: Myung Ha
authors.initials: MH
authors.lastname: Yoon
authors.forename: Jeong Il
authors.initials: JI
authors.lastname: Choi
authors.forename: Hong Beom
authors.initials: HB
authors.lastname: Bae
authors.forename: Seong Wook
authors.initials: SW
authors.lastname: Jeong
authors.forename: Sung Su
authors.initials: SS
authors.lastname: Chung
authors.forename: Kyung Yeon
authors.initials: KY
authors.lastname: Yoo
authors.forename: Chang Young
authors.initials: CY
authors.lastname: Jeong
authors.forename: Seok Jae
authors.initials: SJ
authors.lastname: Kim
authors.forename: Sung Tae
authors.initials: ST
authors.lastname: Chung
authors.forename: Chang Mo
authors.initials: CM
authors.lastname: Kim
mesh_terms: D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000700:Analgesics / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D005557:Formaldehyde / Q000009:adverse effects; D005905:Glyburide / Q000378:metabolism; D007278:Injections, Spinal; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D010069:Oxadiazoles / Q000378:metabolism; D010146:Pain / Q000139:chemically induced; D010147:Pain Measurement / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D011688:Purinones / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D011810:Quinoxalines / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000378:metabolism
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D000700:Analgesics; D010069:Oxadiazoles; D010726:Phosphodiesterase Inhibitors; D015221:Potassium Channels; D011688:Purinones; D011810:Quinoxalines; D005557:Formaldehyde; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D015106:3',5'-Cyclic-GMP Phosphodiesterases; C011145:zaprinast; D006152:Cyclic GMP; D005905:Glyburide