It is well known that
adenine-based
purines exert multiple effects on
pain transmission. However, less attention has been given to the potential effects of
guanine-based
purines (GBPs) on
pain transmission. The aim of this study was to investigate the effects of intracerebroventricular (i.c.v.)
guanosine and GMP on mice
pain models. Mice received an i.c.v. injection of vehicle (saline or 10 muM NaOH),
guanosine (5 to 400 nmol), or GMP (240 to 960 nmol). Additional groups were also pre-treated with i.c.v. injection of the A(1)/A(2A) antagonist
caffeine (15 nmol), the non-selective
opioid antagonist naloxone (12.5 nmol), or the
5'-nucleotidase inhibitor
AOPCP (1 nmol). Measurements of CSF
purine levels and cortical
glutamate uptake were performed
after treatments.
Guanosine and GMP produced dose-dependent antinociceptive effects. Neither
caffeine nor
naloxone affected
guanosine antinociception. Pre-treatment with
AOPCP completely prevented GMP antinociception, indicating that conversion of GMP to
guanosine is required for its antinociceptive effects. Intracerebroventricular administration of
guanosine and GMP induced, respectively, a 180- and 1800-fold increase on CSF
guanosine levels.
Guanosine was able to prevent the decrease on cortical
glutamate uptake induced by intraplantar
capsaicin. This study provides new evidence on the mechanism of action of GBPs, with
guanosine and GMP presenting antinociceptive effects in mice. This effect seems to be independent of
adenosine and
opioid receptors; it is, however, at least partially associated with modulation of the glutamatergic system by
guanosine.