Sildenafil and glyceryl trinitrate reduce tactile allodynia in streptozotocin-injected rats.
The possible antiallodynic effect of phosphodiesterase 5 inhibitor sildenafil and nitric oxide donor glyceryl trinitrate as well as the changes in phosphodiesterase 5A2 mRNA expression in dorsal root ganglion and spinal cord of allodynic diabetic rats was assessed. Diabetes was induced by streptozotocin (50mg/kg, i.p.) in male Wistar rats. Streptozotocin injection produced hyperlglycemia, polydipsia, polyphagia and polyuria as well as long-term tactile allodynia (12 weeks) and a reduction of phosphodiesterase 5A2 mRNA expression in spinal cord of diabetic rats. Systemic administration of sildenafil (1-5.6 mg/kg, i.p.) reduced tactile allodynia in a dose-dependent manner in diabetic rats. Likewise, glyceryl trinitrate patches (0.2mg/h) also reduced tactile allodynia in diabetic rats. Moreover, both drugs reversed streptozotocin-induced phosphodiesterase 5A2 mRNA expression reduction. Our results indicate that glyceryl trinitrate and sildenafil reduce tactile allodynia in diabetic rats suggesting that nitric oxide and cyclic GMP supply is an important step in their mechanism of action of these drugs in diabetic animals. Data suggest that nitric oxide donors (as glyceryl trinitrate) and drugs which increase cyclic GMP levels (as sildenafil) could have a role in the pharmacotherapy of tactile allodynia in diabetic patients.
Araiza-Saldaña
Claudia I
CI
Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur, México, D.F., Mexico.
Rocha-González
Héctor I
HI
Ambriz-Tututi
Mónica
M
Castañeda-Corral
Gabriela
G
Caram-Salas
Nadia L
NL
Hong
Enrique
E
Granados-Soto
Vinicio
V
D000279:Administration, Cutaneous; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000235:genetics / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006930:Hyperalgesia / Q000188:drug therapy*; D007527:Isoenzymes; D008297:Male; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000627:therapeutic use*; D005996:Nitroglycerin / Q000008:administration & dosage / Q000627:therapeutic use*; D010147:Pain Measurement; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D011687:Purines / Q000008:administration & dosage / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000068677:Sildenafil Citrate; D013311:Streptozocin; D013450:Sulfones / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D014110:Touch
D000700:Analgesics; D007527:Isoenzymes; D020030:Nitric Oxide Donors; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D012333:RNA, Messenger; D013450:Sulfones; D013311:Streptozocin; D000068677:Sildenafil Citrate; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D005996:Nitroglycerin