Stress-induced analgesia prevents the development of the tonic, late phase of pain produced by subcutaneous formalin.

Subcutaneous injection of formalin produces a biphasic pain response: a transient early phase followed by a tonic late phase. It has recently been suggested that development of the late phase depends upon the presence of the early one. In support of this suggestion, we now demonstrate that blocking the early phase by stress-induced analgesia prevents development of the late phase, whereas the same stressor given after the first phase does not. Both phases are manifested when stress-induced analgesia is blocked by the N-methyl-D-aspartate (NMDA) or opiate antagonists, MK-801 and naloxone.