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Titolo:
The effect of ABT-702, a novel adenosine kinase inhibitor, on the responses of spinal neurones following carrageenan inflammation and peripheral nerve injury
Autore:
Suzuki, R; Stanfa, LC; Kowaluk, EA; Williams, M; Jarvis, MF; Dickenson, AH;
Indirizzi:
Univ London Univ Coll, Dept Pharmacol, London WC1E 6BT, England Univ London Univ Coll London England WC1E 6BT , London WC1E 6BT, England Abbott Labs, Neurol & Urol Dis Res, Abbott Pk, IL 60064 USA Abbott Labs Abbott Pk IL USA 60064 Urol Dis Res, Abbott Pk, IL 60064 USA
Titolo Testata:
BRITISH JOURNAL OF PHARMACOLOGY
fascicolo: 7, volume: 132, anno: 2001,
pagine: 1615 - 1623
SICI:
0007-1188(200104)132:7<1615:TEOAAN>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
R-PHENYLISOPROPYL-ADENOSINE; DORSAL HORN NEURONS; RAT MODEL; NEUROPATHIC PAIN; ANTIINFLAMMATORY PROPERTIES; INTRATHECAL ADENOSINE; RECEPTOR AGONIST; ANTINOCICEPTION; NOCICEPTION; DEAMINASE;
Keywords:
electrophysiology; spinal nerve ligation; neuropathic pain; carrageenan inflammation; adenosine kinase inhibitor; adenosine;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Suzuki, R Univ London Univ Coll, Dept Pharmacol, Gower St, London WC1E 6BT, England Univ London Univ Coll Gower St London England WC1E 6BT England
Citazione:
R. Suzuki et al., "The effect of ABT-702, a novel adenosine kinase inhibitor, on the responses of spinal neurones following carrageenan inflammation and peripheral nerve injury", BR J PHARM, 132(7), 2001, pp. 1615-1623

Abstract

1 Adenosine (ADO) receptor activation modulates sensory transmission in the dorsal horn. Little is known about the circumstances underlying release of the purine. The present study was conducted to investigate the effect of a novel and potent non-nucleoside adenosine kinase (AK) inhibitor, ABT-702,on the responses of dorsal horn neurones to selected peripheral stimuli. ABT-702 is orally effective to reduce behavioural signs of nociception in models of acute, inflammatory, and neuropathic pain.2 Electrophysiological recordings were made from wide dynamic range (WDR) neurones in halothane-anaesthetized rats. ABT-702 was given subcutaneously following either carrageenan inflammation or peripheral nerve injury (L5/L6spinal nerve ligation). Comparisons were made between carrageenan and uninjected control animals, and similarly between spinal nerve ligated (SNL) and sham operated animals.3 ABT-702 produced inhibition of the postdischarge, wind-up and C-fibre evoked responses in both carrageenan and nerve-injured animals. Furthermore, the mechanical and thermal evoked responses were similarly reduced in SNL rats. Overall, ABT-702 produced a significantly greater inhibition of these responses in SNL rats as compared to sham controls. Similarly ABT-702 tended to produce greater effects after carrageenan inflammation, however this did not reach significance.4 Protection of endogenous adenosine by ABT-702 therefore produces a marked inhibition of the noxious evoked neuronal activity in inflamed and neuropathic rats. Our results demonstrate a plasticity in the endogenous adenosine-mediated inhibitory system following SNL and provide a possible basis forthe use of this compound for the treatment of neuropathic and other persistent pain states.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/07/20 alle ore 21:01:44