Potentiation of formalin-evoked adenosine release by an adenosine kinase inhibitor and an adenosine deaminase inhibitor in the rat hind paw: a microdialysis study

The present study examined the effects of local subcutaneous administration of formalin on adenosine release from the rat hind paw, and the effects of inhibitors of adenosine metabolism on such release. Microdialysis probes w ere inserted into the subcutaneous tissue of the plantar surface of rat hin d paws. Samples were collected every 10 min at a perfusion rate of 2 mul/mi n and high performance liquid chromatography was used to measure adenosine levels. At lower concentrations of formalin (0.5-2.5%), a significant incre ase in adenosine levels was observed in the first 10 min after formalin inj ection, while at the highest concentration of formalin (5%), the increase i n adenosine release was observed over 60 min. Go-administration of the aden osine kinase inhibitor 5'-amino-5'-deoxyadenosine (100 nmol) with formalin, significantly increased adenosine release evoked by 0.5-1.5% formalin, but did not produce a further enhancement of release evoked by 5% formalin. Th e adenosine deaminase inhibitor 2/-deoxycoformycin (100 nmol) significantly increased adenosine levels at 5% formalin but had no effect at lower conce ntrations of formalin. In confirmation of previous studies, subcutaneous in jection of formalin (0.5-5%) produced a characteristic biphasic concentrati on-related expression of nociceptive behaviours and an increase in paw volu me. This study directly demonstrates that formalin can evoke a concentratio n-dependent local release of adenosine from the rat hind paw. The ability o f an adenosine kinase inhibitor and an adenosine deaminase inhibitor to mod ulate this release is dependent on substrate adenosine concentrations. (C) 2000 Elsevier Science B.V. All rights reserved.