Fundamental & clinical pharmacology
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Fundam Clin Pharmacol · Apr 2007
ReviewChronic neuropathic pain: mechanisms, drug targets and measurement.
Neuropathic pain is common in many diseases or injuries of the peripheral or central nervous system, and has a substantial impact on quality of life and mood. Lesions of the nervous system may lead to potentially irreversible changes and imbalance between excitatory and inhibitory systems. ⋯ Valid and reliable tools to assess various symptoms and signs in neuropathic pain and knowledge of drug mechanisms are prerequisites for pursuing this approach. The present review summarizes mechanisms of neuropathic pain, targets of currently used drugs, and measures used in neuropathic pain trials.
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Fundam Clin Pharmacol · Feb 2007
Effect of resveratrol, a polyphenolic phytoalexin, on thermal hyperalgesia in a mouse model of diabetic neuropathic pain.
Diabetic neuropathic pain, an important microvascular complication in diabetes mellitus, has been recognized as one of the most difficult types of pain to treat. The underlying mechanisms of painful symptoms may be closely associated with hyperglycaemia but a lack of the understanding of its proper aetiology, inadequate relief, development of tolerance and potential toxicity of classical antinociceptives warrant the investigation of the newer agents to relieve this pain. The aim of the present study was to explore the antinociceptive effect of resveratrol on diabetic neuropathic pain and to examine its effect on serum tumour necrosis factor-alpha (TNF-alpha) and whole brain nitric oxide (NO) release. ⋯ Daily treatment with resveratrol (5, 10 and 20 mg/kg body weight; p.o.) for 4 weeks starting from the 4th week of STZ injection significantly attenuated thermal hyperalgesia. Resveratrol also decreased the serum TNF-alpha levels and whole brain NO release in a dose-dependent manner. These results point towards the potential of resveratrol in attenuating diabetic neuropathic pain.
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Fundam Clin Pharmacol · Oct 2006
Involvement of endogenous opioid peptides and nitric oxide in the blunted chronotropic and inotropic responses to beta-adrenergic stimulation in cirrhotic rats.
It is well known that chronotropic and inotropic responses to beta-adrenergic stimulation are impaired in cirrhosis, but the exact reason is not clear. Considering the inhibitory effect of endogenous opioid peptides and nitric oxide (NO) on beta-adrenergic pathway, we examined their roles in hyporesponsiveness of isolated atria and papillary muscles to isoproterenol stimulation in cirrhotic rats. Cirrhosis was induced by chronic bile duct ligation. ⋯ Concurrent administration of naltrexone and L-NAME also restored to normal the basal abnormalities and the blunted responses to isoproterenol in cirrhotic rats, and did not show any antagonistic effect. Based on these findings, both the endogenous opioid peptides and NO may be involved in the attenuated chronotropic and inotropic responses to beta-adrenergic stimulation in cirrhosis. It seems that the iNOS activity results in NO-induced hyporesponsiveness to beta-adrenergic stimulation in cirrhosis.
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The present study monitored medication prescribing patterns to patients treated for upper respiratory tract infections (URTIs) in the pediatric outpatient department (OPD) at Central Referral Hospital (CRH), Gangtok, Sikkim. A total of 562 URTI prescriptions of children, aged 0-12 years attending pediatric OPD at CRH, Sikkim were collected by a random once-weekly survey between May 2002 and April 2003. Males numbered 284 (50.5%), and females 278 (49.5%). ⋯ Medication selection was rational in few cases. Various anomalies were observed in various aspects of drug use in children for URTI's. The main aim of the initiative is the need for more rational medicine use in URTIs in children for improvement of clinical effectiveness, cost effectiveness and reduction of potential useless risk of side effects.
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Fundam Clin Pharmacol · Aug 2006
Comparative StudyThe antinociceptive activity of Muntingia calabura aqueous extract and the involvement of L-arginine/nitric oxide/cyclic guanosine monophosphate pathway in its observed activity in mice.
The present study was carried out to investigate on the possible involvement of L-arginine/nitric oxide/cyclic guanosine monophosphate (L-arginine/NO/cGMP) pathway in the aqueous extract of Muntingia calabura (AEMC) leaves antinociception in mice assessed by abdominal constriction test. The AEMC, obtained by soaking the dried leaves in distilled water (DH(2)O) (1 : 2; w/v) for 24 h, was prepared in concentrations of 10%, 50% and 100% that were approximately equivalent to doses of 27, 135 and 270 mg/kg, and administered subcutaneously (s.c.) 5 min after pre-treatment (s.c.) of mice with DH(2)O, L-arginine (20 mg/kg), N(G)-monomethyl-L-arginine acetate (L-NMMA; 20 mg/kg), N(G)-nitro-L-arginine methyl esters (L-NAME; 20 mg/kg), methylene blue (MB) (20 mg/kg), respectively. The AEMC was found to exhibit a concentration-dependent antinociception after pre-challenge with DH(2)O. ⋯ Except for the higher concentration of AEMC used, co-treatment with L-NAME was found to insignificantly and significantly (P < 0.05) reverse the L-arginine effect when given alone or with low concentration AEMC, respectively. In addition, co-treatment with MB significantly (P < 0.05) reversed the L-arginine effect when given alone or with 10% concentration AEMC but failed to affect the activity of the rest of concentrations used. As a conclusion, this study has demonstrated the involvement of L-arginine/NO/cGMP pathway in AEMC antinociception.