Intrathecal administration of
substance P at the lower thoracic spinal level has an antinociceptive effect on reaction time in the tail-flick test; this response is blocked by
naloxone i.v. but not by i.v. administration of
opiate antagonists which do not cross the blood-brain barrier. As
morphine-induced
analgesia is blocked by
adenosine antagonists, to determine whether this
substance P-induced,
opioid-mediated antinociception also includes a
purine link, the
adenosine receptor antagonist,
caffeine, was given systemically 10 min prior to
substance P administration. In control rats pretreated with saline,
substance P (6.5 nmol) produced an increase in reaction time to about 160% of preadministration values at one min after
intrathecal injection. The effect could also be observed at 6 min after this injection. Pretreatment with 16 or with 32 mg/kg of
caffeine i.p. blocked the response to
substance P, and produced a
hyperalgesia similar to that reported in studies at the lumbo-sacral spinal level. These results indicate that the adrenal
opioid-induced antinociception observed upon intrathecal administration of
substance P at the lower thoracic level occurs via an
adenosine link. This is the first demonstration of a
purine link in the expression of antinociceptive effects of an endogenously released
opioid.