Possible involvement of brain-derived neurotrophic factor in the antinociceptive effect of antidepressants in neuropathic pain

Neuropathic pain, a chronic pain state caused by injury to the nervous system, usually responds poorly to standard pain treatment. Antidepressants have been used to treat neuropathic pain, and animal and clinical studies have showed beneficial effects. However, the mechanisms underlying antidepressant antinociceptive effect in neuropathic pain are still unknown. Brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, can modulate synaptic plasticity and neurotransmitter release across multiple neurotransmitter systems. Recent animal and human studies have demonstrated that antidepressants can increase central as well as plasma BDNF levels. In addition: (1) BDNF is produced by a subset of primary sensory neurons that are located in the dorsal root ganglion; (2) BDNF levels change in animal models of neuropathic pain; (3) BDNF can indirectly depress sensory neuron transmission in the dorsal horn. From these findings, it is proposed that BDNF may play an important role in the antidepressant antinociceptive effect in neuropathic pain. The notion of BDNF mediating the therapeutic mechanisms of antidepressant in neuropathic pain may help to select the specific type and the optimal dose of antidepressants for the treatment of neuropathic pain. Exploration of this hypothesis could provide a new direction in the treatment of neuropathic pain, as well as other pain disorders.