ANTINOCICEPTIVE EFFECT OF BRAIN-DERIVED NEUROTROPHIC FACTOR AND NEUROTROPHIN-3

Infusions of brain-derived neurotrophic factor (BDNF) or neurotrophin- 3 (NT-3), but not nerve-growth factor, into the rat midbrain significa ntly elevated the tail-flick response latency. Analgesia was observed as soon as 24 h after the onset of infusion, reached maximum levels by day 5 and remained constant for at least an additional 6 days, sugges ting no development of tolerance. BDNF infusion also increased latency in the hot-plate test. Naloxone administration reversed the BDNF-indu ced increase in the tail-flick latency. The antinociceptive effect of BDNF infusion was accompanied by an augmentation in serotonergic activ ity within the brain and spinal cord. These data demonstrate both an e ffect of BDNF and NT-3 on serotonergic neurons and an analgesic proper ty of these neurotrophins which appears to involve both serotonin and opioid mechanisms.