ABSTRACT
The Fischer 344 (F344) rat strain differs from the Lewis strain in the response to neuropathic pain. Recently, we found that F344 rats totally recover from mechanical allodynia induced by chronic constriction injury (CCI) of the sciatic nerve 28 days after surgery whereas Lewis rats are initiating their recovery at this time point. Thus, the use of this neuropathic pain model in these different rat strains constitutes a good strategy to identify possible target genes involved in the development of neuropathic pain. Since differences between Lewis and F344 rats in their response to pain stimuli in acute pain models have been related to differences in the endogenous opioid and noradrenergic systems, we aimed to determine the levels of expression of key genes of both systems in the spinal cord and dorsal root ganglia (DRG) of both strains 28 days after CCI surgery. Real time RT-PCR revealed minimal changes in gene expression in the spinal cord after CCI despite the strain considered, but marked changes in DRG were observed. A significant upregulation of prodynorphin gene expression occurred only in injured DRG of F344 rats, the most resistant strain to neuropathic pain. In addition, we found a significant downregulation of tyrosine hydroxylase and proenkephalin gene expression levels in both strains whereas delta-opioid receptor was found to be significantly downregulated only in injured DRG of Lewis rats although the same trend was observed in F344 rats. The data strongly suggest that dynorphins could be involved in strain differences concerning CCI resistance.
Subject(s)
Dynorphins/biosynthesis , Ganglia, Spinal/metabolism , Gene Expression Regulation/genetics , Neurons, Afferent/metabolism , Norepinephrine/biosynthesis , Peripheral Nervous System Diseases/metabolism , Animals , Chronic Disease , Denervation , Disease Models, Animal , Down-Regulation/genetics , Enkephalins/genetics , Ganglia, Spinal/cytology , Hyperalgesia/genetics , Hyperalgesia/metabolism , Hyperalgesia/physiopathology , Ligation , Male , Neurons, Afferent/cytology , Peripheral Nerve Injuries , Peripheral Nerves/metabolism , Peripheral Nerves/physiopathology , Peripheral Nervous System Diseases/genetics , Peripheral Nervous System Diseases/physiopathology , Protein Precursors/genetics , RNA, Messenger/metabolism , Rats , Rats, Inbred F344 , Rats, Inbred Lew , Receptors, Opioid, delta/genetics , Reverse Transcriptase Polymerase Chain Reaction , Species Specificity , Spinal Cord/cytology , Spinal Cord/metabolism , Tyrosine 3-Monooxygenase/geneticsABSTRACT
The Fischer 344 (F344) rat inbred strain differs from the inbred Lewis and the outbred Sprague-Dawley (SD) in the response to different pain stimuli, which has been partially attributed to differences in the endogenous opioid and noradrenergic systems. Since brain-derived neutrophic factor (BDNF) modulates both the endogenous opioid and noradrenergic systems, we have now studied specific changes in BDNF gene expression related to the maintenance of neuropathic pain in the three rat strains. F344 rats were found to be the only strain that completely recovered from neuropathic pain (mechanical allodynia) 28 days after chronic constriction injury (CCI) of the sciatic nerve. Real time RT-PCR studies revealed minimal changes in the expression of BDNF in the spinal cord after CCI despite the strain considered, but marked changes in dorsal root ganglia (DRG) were observed. A significant upregulation of BDNF gene expression was found only in injured DRG of F344 rats, thus correlating with higher resistance to neuropathic pain. The data suggest that BDNF could be involved in strain differences concerning CCI resistance.
