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 significantly 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, suggesting no development of tolerance. BDNF infusion also increased latency in the hot-plate test. Naloxone administration reversed the BDNF-induced increase in the tail-flick latency. The antinociceptive effect of BDNF infusion was accompanied by an augmentation in serotonergic activity within the brain and spinal cord. These data demonstrate both an effect of BDNF and NT-3 on serotonergic neurons and an analgesic property of these neurotrophins which appears to involve both serotonin and opioid mechanisms.