Title:Interplay of BDNF and GDNF in the Mature Spinal Somatosensory System and Its Potential Therapeutic Relevance
Volume: 19
Issue: 8
Author(s): Francesco Ferrini, Chiara Salio, Elena M. Boggio and Adalberto Merighi*
Affiliation:
- Department of Veterinary Sciences, University of Turin, Grugliasco,Italy
Keywords:
BDNF, GDNF, nociception, spinal dorsal horn, chronic pain, neuropathic pain.
Abstract: The growth factors BDNF and GDNF are gaining more and more attention as modulators
of synaptic transmission in the mature central nervous system (CNS). The two molecules undergo
a regulated secretion in neurons and may be anterogradely transported to terminals where
they can positively or negatively modulate fast synaptic transmission. There is today a wide consensus
on the role of BDNF as a pro-nociceptive modulator, as the neurotrophin has an important part
in the initiation and maintenance of inflammatory, chronic, and/or neuropathic pain at the peripheral
and central level. At the spinal level, BDNF intervenes in the regulation of chloride equilibrium
potential, decreases the excitatory synaptic drive to inhibitory neurons, with complex changes in
GABAergic/glycinergic synaptic transmission, and increases excitatory transmission in the superficial
dorsal horn. Differently from BDNF, the role of GDNF still remains to be unraveled in full.
This review resumes the current literature on the interplay between BDNF and GDNF in the regulation
of nociceptive neurotransmission in the superficial dorsal horn of the spinal cord. We will first
discuss the circuitries involved in such a regulation, as well as the reciprocal interactions between
the two factors in nociceptive pathways. The development of small molecules specifically targeting
BDNF, GDNF and/or downstream effectors is opening new perspectives for investigating these
neurotrophic factors as modulators of nociceptive transmission and chronic pain. Therefore, we
will finally consider the molecules of (potential) pharmacological relevance for tackling normal
and pathological pain.
