Premium
The effect of ABT‐702, a novel adenosine kinase inhibitor, on the responses of spinal neurones following carrageenan inflammation and peripheral nerve injury
Author(s) -
Suzuki Rie,
Stanfa Louise C,
Kowaluk Elizabeth A,
Williams Michael,
Jarvis Michael F,
Dickenson Anthony H
Publication year - 2001
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703972
Subject(s) - adenosine , nociception , medicine , neuropathic pain , peripheral nerve injury , nociceptor , pharmacology , carrageenan , nerve injury , adenosine kinase , spinal cord , anesthesia , neuroscience , adenosine deaminase , receptor , biology , sciatic nerve , psychiatry
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. 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. 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. 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.British Journal of Pharmacology (2001) 132 , 1615–1623; doi: 10.1038/sj.bjp.0703972