title: Involvement of NO-cGMP pathway in anti-hyperalgesic effect of PDE5 inhibitor tadalafil in experimental hyperalgesia.
abstract: The association of elevated level of cyclic guanosine monophosphate (cGMP) with inhibition of hyperalgesia and involvement of nitric oxide (NO)-cGMP pathway in the modulation of pain perception was previously reported. Phosphodiesterases 5 (PDE5) inhibitors, sildenafil and tadalafil (TAD) used in erectile dysfunction, are known to act via the NO-cGMP pathway. TAD exerts its action by increasing the levels of intracellular cGMP. Hence, the present study investigated the effect of TAD 5, 10, or 20 mg/kg, per os (p.o.) or L-NAME 20 mg/kg, intraperitoneally (i.p.) and TAD (20 mg/kg, p.o.) in carrageenan- and diabetes-induced hyperalgesia in rats using hot plate test at 55 ± 2 °C. In carrageenan- and diabetes-induced hyperalgesia, TAD (10 and 20 mg/kg, p.o.) significantly increased paw withdrawal latencies (PWLs) as compared to the control group. L-NAME significantly decreased PWLs as compared to the normal group and aggravated the hyperalgesia. Moreover, significant difference in PWLs of L-NAME and TAD 20 was evident. Co-administration of L-NAME (20 mg/kg) with TAD (20 mg/kg) showed significant difference in PWLs as compared to the TAD (20 mg/kg), indicating L-NAME reversed and antagonized TAD-induced anti-hyperalgesia. This suggested an important role of NO-cGMP pathway in TAD-induced anti-hyperalgesic effect.
authors.affiliation: Department of Pharmacology, SNJB's SSJ College of Pharmacy, Neminagar, Chandwad, Dist. Nashik, India, 423101, kvotari76@rediffmail.com.
authors.forename: K V
authors.initials: KV
authors.lastname: Otari
authors.forename: C D
authors.initials: CD
authors.lastname: Upasani
mesh_terms: D000818:Animals; D002351:Carrageenan / Q000633:toxicity; D006152:Cyclic GMP / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000068581:Tadalafil / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D009569:Nitric Oxide; D000068581:Tadalafil; D002351:Carrageenan; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester