BDNF as a pain modulator

https://doi.org/10.1016/j.pneurobio.2008.04.004Get rights and content

Abstract

At least some neurotrophins may be powerful modulators of synapses, thereby influencing short- and long-term synaptic efficiency. BDNF acts at central synapses in pain pathways both at spinal and supraspinal levels. Neuronal synthesis, subcellular storage/co-storage and release of BDNF at these synapses have been characterized on anatomical and physiological grounds, in parallel with trkB (the high affinity BDNF receptor) distribution. Histological and functional evidence has been provided, mainly from studies on acute slices and intact animals, that BDNF modulates fast excitatory (glutamatergic) and inhibitory (GABAergic/glycinergic) signals, as well as slow peptidergic neurotrasmission in spinal cord. Recent studies have unraveled some of the neuronal circuitries and mechanisms involved, highlighting the key role of synaptic glomeruli in lamina II as the main sites for such a modulation.

Section snippets

General concepts

Neurotrophins (NTs) are a well characterized family of growth factors playing important roles in regulating neuronal survival, growth and differentiation (Davies, 1994, Snider, 1994). Besides this, at least some NTs may be powerful modulators of synapses, thereby influencing short- and long-term synaptic efficiency (Berninger and Poo, 1996, Lewin and Barde, 1996, Snider, 1994, Thoenen, 1995).

Among the members of the NT family, the brain-derived neurotrophic factor (BDNF) is a 12.4-kDa basic

Anatomical evidence for BDNF as a pain modulator

The availability of specific antibodies and tracing techniques has made it possible to unravel the cellular localization and distribution of BDNF and its high affinity receptor in central and peripheral neurons. Histological data which are relevant to the role of BDNF as a pain modulator are reported in this section.

Functional evidence for BDNF as a pain modulator

The seminal paper by Kafitz et al. (1999) was one of the first to show that BDNF excited neurons in the hippocampus, cortex and cerebellum as rapidly as the neurotransmitter glutamate, even at a more than thousand-fold lower concentration. This opened the way to a series of investigations aiming to dissect out the role of the NT as a fast synaptic transmitter. Functional data on the role of BDNF at synapses involved in pain neurotransmission are reported below.

BDNF actions on pain behavior

Behavioral data on the effects of BDNF in mediating nociceptive responses are summarized in Table 2. The involvement of the endogenous NT in acute pain is still controversial: although some studies reported a change in nociceptive behavior by neutralizing BDNF in dorsal horn, the high frequency stimulation pattern required for NT release would argue against an important role in basal nociception. Intrathecal administration of BDNF seemed to evoke, in some cases, a pro-nociceptive response,

Future perspectives and concluding remarks

The picture emerging from currently available data on the modulatory role of BDNF in pain pathways is still largely incomplete and fragmentary.

This is true at not only the supraspinal level, but also in spinal cord and particularly lamina II, which represents the most widely investigated area so far.

Although many of the cellular mechanisms by which the NT exerts it function at synapses have been clarified, still it remains to understand the circuitry that is ultimately responsible for the

Acknowledgements

The experimental work described in this paper has been funded by grants from the University of Turin, Compagnia di San Paolo Torino and Italian MiUR. We are greatly indebted to Gianfranco Zanutto for graphic artwork.

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