Involvement of primary sensory afferents, postganglionic sympathetic nerves and mast cells in the formalin-evoked peripheral release of adenosine

Injection of formalin into the rat hind paw produces a dose-dependent local peripheral release of adenosine. Low doses of formalin (0.5-2.5%) evoke re lease during the first 10 min following injection, while a high dose of for malin (5%) evokes release lasting for 60 min. The current study was designe d to determine the possible origin of release produced by two doses of form alin (1.5% and 5%). Microdialysis probes were implanted into the subcutaneo us tissue under the glabrous skin of the hind paw of anaesthetized rats, an d adenosine was determined by high performance Liquid chromatography. Pretr eatment with capsaicin, a neurotoxin selective for unmyelinated small diame ter primary afferent nerves, markedly reduced the adenosine released by 1.5 % formalin and the early phase of release by 5% formalin. Acute injection o f 1% capsaicin to the hind paw of untreated rats also induced adenosine rel ease. Pretreatment with 6-hydroxydopamine, a neurotoxin selective for sympa thetic postganglionic nerve terminals, had no effect on release evoked by 1 .5% formalin, but significantly reduced adenosine release during the late p hase of release induced by 5% formalin. Pretreatment with compound 48/80, w hich degranulates mast cells, had no effect on adenosine release evoked by either concentration of formalin. We conclude that the origin of the adenos ine released peripherally by formalin depends on the formalin concentration . At the lower concentration (1.5%), release is predominately from unmyelin ated sensory afferent nerve terminals, while at the higher concentration (5 %), unmyelinated afferent nerve terminals are involved in the early phase, while sympathetic postganglionic nerve terminals are involved in the later phase. Mast cells do not contribute to release of adenosine evoked by eithe r concentration of formalin. (C) 2001 Elsevier Science BN. Ail rights reser ved.