RGD Reference Report - Spinal brain-derived neurotrophic factor (BDNF) produces hyperalgesia in normal mice while antisense directed against either BDNF or trkB, prevent inflammation-induced hyperalgesia.

General

Spinal brain-derived neurotrophic factor (BDNF) produces hyperalgesia in normal mice while antisense directed against either BDNF or trkB, prevent inflammation-induced hyperalgesia.
Authors:	Groth, R Aanonsen, L
Citation:	Groth R and Aanonsen L, Pain. 2002 Nov;100(1-2):171-81.
RGD ID:	8657101
Pubmed:	PMID:12435470 (View Abstract at PubMed)
Although known primarily for its role in neuronal development, brain-derived neurotrophic factor (BDNF) has also recently been implicated in processes mediated by the adult nervous system, such as spinal nociception. Peripheral inflammation increases expression of BDNF preferentially in dorsal root ganglion cells that contain substance P and/or calcitonin gene-related peptide, known nociceptive transmitters for which synthesis is also increased during inflammatory states. Expression of the tyrosine kinase receptor that selectively binds BDNF, trkB, is increased in the spinal dorsal horn during inflammation as well. Additionally, intrathecal (i.t.) administration of the BDNF-scavenging protein trkB-IgG attenuates inflammation-induced behavioral responses. Collectively, this evidence implicates BDNF in spinal nociceptive processes. Here we show that, in normal mice, i.t. BDNF produces an acute, dose-dependent thermal hyperalgesic response. Selective inhibition of BDNF expression by i.t. antisense oligodeoxynucleotide treatment produces antinociception in normal mice and attenuates carrageenan-induced hyperalgesia. Further, we demonstrate that i.t. antisense treatment directed against the full-length trkB receptor (trkB.FL) attenuates carrageenan-induced hyperalgesia. Consistent with a trkB.FL-mediated mechanism, the i.t. administration of another trkB ligand, neurotrophin-4/5, also produces hyperalgesia while the trkC agonist neurotrophin-3, which weakly cross-reacts with trkB, has little effect. Finally, with the accumulating evidence linking BDNF to synaptic plasticity, we investigated whether BDNF-induced hyperalgesia in normal mice involves the N-methyl-D-aspartate (NMDA) receptor. Interestingly, i.t. co-administration of the NMDA receptor antagonist D(-)-2-amino-5-phosphonovaleric acid (D-APV) with BDNF dose-dependently inhibits BDNF-induced hyperalgesia, suggesting that BDNF induces acute hyperalgesic responses and affects central sensitization in a process dependent on NMDA receptor activation.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
Hyperalgesia		ISO	Bdnf (Mus musculus)	8657101; 8657101	associated with Peripheral Nerve Injuries	RGD
Hyperalgesia		IMP		8657101	associated with Peripheral Nerve Injuries	RGD

Objects Annotated

Genes (Rattus norvegicus)

Bdnf (brain-derived neurotrophic factor)

Genes (Mus musculus)

Bdnf (brain derived neurotrophic factor)

Genes (Homo sapiens)

BDNF (brain derived neurotrophic factor)

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Spinal brain-derived neurotrophic factor (BDNF) produces hyperalgesia in normal mice while antisense directed against either BDNF or trkB, prevent inflammation-induced hyperalgesia.