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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 Pharmacol. 2001 Apr; 132(7):1615-23.BJ

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/L6 spinal 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 for the use of this compound for the treatment of neuropathic and other persistent pain states.

Authors+Show Affiliations

Department of Pharmacology, University College London, Gower Street, London, WC1E 6BT. ucklrsu@ucl.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11264257

Citation

Suzuki, R, 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." British Journal of Pharmacology, vol. 132, no. 7, 2001, pp. 1615-23.
Suzuki R, Stanfa LC, Kowaluk EA, 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 Pharmacol. 2001;132(7):1615-23.
Suzuki, R., Stanfa, L. C., Kowaluk, E. A., Williams, M., Jarvis, M. F., & Dickenson, A. H. (2001). The effect of ABT-702, a novel adenosine kinase inhibitor, on the responses of spinal neurones following carrageenan inflammation and peripheral nerve injury. British Journal of Pharmacology, 132(7), 1615-23.
Suzuki R, 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 Pharmacol. 2001;132(7):1615-23. PubMed PMID: 11264257.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of ABT-702, a novel adenosine kinase inhibitor, on the responses of spinal neurones following carrageenan inflammation and peripheral nerve injury. AU - Suzuki,R, AU - Stanfa,L C, AU - Kowaluk,E A, AU - Williams,M, AU - Jarvis,M F, AU - Dickenson,A H, PY - 2001/3/27/pubmed PY - 2001/5/18/medline PY - 2001/3/27/entrez SP - 1615 EP - 23 JF - British journal of pharmacology JO - Br J Pharmacol VL - 132 IS - 7 N2 - 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/L6 spinal 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 for the use of this compound for the treatment of neuropathic and other persistent pain states. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/11264257/The_effect_of_ABT_702_a_novel_adenosine_kinase_inhibitor_on_the_responses_of_spinal_neurones_following_carrageenan_inflammation_and_peripheral_nerve_injury_ L2 - https://doi.org/10.1038/sj.bjp.0703972 DB - PRIME DP - Unbound Medicine ER -