Neonatal Maternal Separation Increases Brain-Derived Neurotrophic Factor and Tyrosine Kinase Receptor B Expression in the Descending Pain Modulatory System

Abstract

Neonatal maternal separation (NMS) could trigger long-term changes in the central neuronal responses to nociceptive stimuli in rats. Stress-induced visceral hyperalgesia is closely associated with the dysfunction of descending pain modulatory systems. Brain-derived neurotrophic factor (BDNF) not only has an important role in long-term synaptic plasticity but also in facilitating descending pain. The present study aimed to investigate changes in the expression of BDNF and its receptor tyrosine kinase receptor B (TrkB) in the amygdala and the rostral ventromedial medulla (RVM) after NMS and colorectal distention (CRD) stimulation in rats. Male Wistar rat pups were subjected to 180 min of daily NMS or not handled for 13 consecutive days. Expression of BDNF and TrkB following NMS and CRD stimulation was determined using immunohistochemistry. The results revealed an increase in the expression of BDNF and TrkB in the amygdala after NMS. An interactive effect of NMS and CRD on the expression of TrkB, but not BDNF, was found in the RVM. Furthermore, a significant interactive effect of NMS and CRD on the colocalization coefficient of TrkB and phospho-extracellular signal-regulated kinase expression in both the amygdala and RVM were found. These data demonstrate that NMS increases BDNF and TrkB expression in the descending pain systems, which may contribute to the development of NMS-induced visceral hyperalgesia.

Differential effects of neonatal maternal separation on the expression of neurotrophic factors in rat brain. II: Regional differences in the cerebellum versus the cerebral cortex

“…Numerous studies have reported that psychological or chronic stress increases the levels of brain-derived neurotrophic factor (BDNF) expression in the hippocampus, striatum amygdala, and ventral tegmental area in rats [8][9][10] . These reports are consistent with the fact that BDNF is one of the most important endogenous mediators of stress responses in the brain 11) .…”

Maternal Deprivation Induces Depressive-like Behaviour and Alters Neurotrophin Levels in the Rat Brain

“…In fact, BDNF expression was found to be increased on PND 17, approximately 3 days after the last maternal deprivation in frontal cortex and hippocampus, and a single 3 h deprivation on PND 17 did not alter the expression of the neurotrophin in control, as well as in deprived rats [48]. Expression of BDNF and its receptor, tyrosine kinase receptor B, increased in amygdala after neonatal maternal separation [16]. In addition, early deprivation also increased BDNF levels the hippocampus and olfactory bulb [49].…”

“…In rodents, several reports indicate that early maternal deprivation affects neurotrophins into adulthood, but results obtained have been contradictory [14][15][16][17][18].…”

Genotype-dependent responsivity to inflammatory pain: A role for TRPV1 in the periaqueductal grey

“…Data from our laboratory demonstrated that pharmacological blockade of CB 1 receptors increased formalin-evoked nociceptive behaviour in WKY rats and blockade of FAAH (enzyme catabolising AEA) decreased the hyperalgesia associated with intra-plantar formalinadministration (Rea et al, 2014). In a separate study, adult Wistar rats exposed to MD (maternal deprivation), exhibited higher levels of tyrosine kinase receptor B in the RVM, which is associated with an increase in visceral hypersensitivity to colorectal distension (Chung et al, 2009). The authors demonstrated no effect on the BDNF expression levels in RVM (Chung et al, 2009), although other changes remain to be investigated.…”

“…In a separate study, adult Wistar rats exposed to MD (maternal deprivation), exhibited higher levels of tyrosine kinase receptor B in the RVM, which is associated with an increase in visceral hypersensitivity to colorectal distension (Chung et al, 2009). The authors demonstrated no effect on the BDNF expression levels in RVM (Chung et al, 2009), although other changes remain to be investigated. The evidence suggests that the RVM does play a role in hyperalgesia associated with negative affective state.…”