ABSTRACT
Title
Investigation on dynorphin and BDNF role in an experimental model of neuropathic pain
Authors
D. Mercatelli
Doctorate School in Pharmacological and Toxicological, Human Development and Movement Sciences
Dept. of Pharmacology - University of Bologna, Italy.
Doctorate School in Pharmacological and Toxicological, Human Development and Movement Sciences
Dept. of Pharmacology - University of Bologna, Italy.
Abstract
Neuropathic pain, caused by different triggering events or diseases, underlies a series of plasticity changes resulting in a state of neural disease [1].
In this study, possible alterations of a series of genes involved in pain transmission and neuroplasticity were investigated, in a murine experimental model of neuropathic pain.
Different groups of ICR CD-1, or BDNF (+/+) and BDNF (+/-) mice were subjected to a right sciatic nerve lesion, according to the chronic constriction injury (CCI) model [2].
The Hargreaves’ plantar test or the acetone and cold plate tests were used to assess the presence and development of behavioural signs of neuropathic pain (i.e. hyperalgesia/ allodynia, respectively), and were performed at different intervals after the sciatic nerve lesion.
mRNA levels for proenkephalin (pENK), prodynorphin (pDYN), pronociceptin (pN/OFQ), pronociceptin opioid receptor (pNOP) and pro brain derived neurotrophic factor (pBDNF) in the L4-L6 portion of the spinal cord, were determined by Real Time RT-PCR.
No significant alterations of all investigated spinal mRNA levels were observed at 14 days after CCI in ICR CD-1, whereas a significant increase of pDYN and pBDNF gene expression was detected at seven days after the lesion.
A later onset of hyperalgesia was observed in BDNF (+/-) mice (seven days after CCI) compared with BDNF (+/+) and with ICR CD-1 mice (three days). In addition, BDNF (+/-) animals exhibited significantly higher signs of allodynia than BDNF(+/+), at seven days after CCI.
Finally, the pDYN gene expression increase observed in the spinal cord of ICR CD-1 mice at seven days after CCI was not detected in lesioned BDNF (+/-) mice.
These data indicate a role for BDNF in the mechanisms underlying the development of allodynia and hyperalgesia, thus confirming its involvement in neuroplasticity leading to neuropathic pain conditions. Furthermore, pDYN gene expression results suggest a role for this opioid peptide in this neural disease and are in agreement with the hypothesis that dynorphin could act as a downstream effector of BDNF actions [3].
1) Costigan M et al. (2009) - Annu Rev Neurosci vol 32:1-32.
2) Bennet GJ and Xie YK. (1988) - Pain vol 33:87-107.
3) Logrip ML et al. (2008) - FASEB J. vol 22:2393-2404.
In this study, possible alterations of a series of genes involved in pain transmission and neuroplasticity were investigated, in a murine experimental model of neuropathic pain.
Different groups of ICR CD-1, or BDNF (+/+) and BDNF (+/-) mice were subjected to a right sciatic nerve lesion, according to the chronic constriction injury (CCI) model [2].
The Hargreaves’ plantar test or the acetone and cold plate tests were used to assess the presence and development of behavioural signs of neuropathic pain (i.e. hyperalgesia/ allodynia, respectively), and were performed at different intervals after the sciatic nerve lesion.
mRNA levels for proenkephalin (pENK), prodynorphin (pDYN), pronociceptin (pN/OFQ), pronociceptin opioid receptor (pNOP) and pro brain derived neurotrophic factor (pBDNF) in the L4-L6 portion of the spinal cord, were determined by Real Time RT-PCR.
No significant alterations of all investigated spinal mRNA levels were observed at 14 days after CCI in ICR CD-1, whereas a significant increase of pDYN and pBDNF gene expression was detected at seven days after the lesion.
A later onset of hyperalgesia was observed in BDNF (+/-) mice (seven days after CCI) compared with BDNF (+/+) and with ICR CD-1 mice (three days). In addition, BDNF (+/-) animals exhibited significantly higher signs of allodynia than BDNF(+/+), at seven days after CCI.
Finally, the pDYN gene expression increase observed in the spinal cord of ICR CD-1 mice at seven days after CCI was not detected in lesioned BDNF (+/-) mice.
These data indicate a role for BDNF in the mechanisms underlying the development of allodynia and hyperalgesia, thus confirming its involvement in neuroplasticity leading to neuropathic pain conditions. Furthermore, pDYN gene expression results suggest a role for this opioid peptide in this neural disease and are in agreement with the hypothesis that dynorphin could act as a downstream effector of BDNF actions [3].
1) Costigan M et al. (2009) - Annu Rev Neurosci vol 32:1-32.
2) Bennet GJ and Xie YK. (1988) - Pain vol 33:87-107.
3) Logrip ML et al. (2008) - FASEB J. vol 22:2393-2404.