Visceral hyperalgesia induced by neonatal maternal separation is associated with nerve growth factor–mediated central neuronal plasticity in rat spinal cord

Chung, Elaine K.Y.; Zhang, X.-J.; Xu, Hong‐Xi; Sung, Joseph J.Y.; Bian, Zhaoxiang

doi:10.1016/j.neuroscience.2007.07.055

Cited by 47 publications

(43 citation statements)

References 50 publications

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“…The RVM forms the primary relay site and exerts a biphasic influence on visceral nociceptive transmission [22,23] . The increased excitability in response to visceral stimuli in the spinal cord after NMS, observed in our previous studies [4,24] , reflects changes in plasticity in descending pain circuitry. Our recent work has shown differential regulation of phospho (p)-Erk and c-Fos expression in the central pain matrix [5] .…”

Section: Introductionmentioning

confidence: 64%

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

et al. 2009

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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.

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Section: Introductionmentioning

confidence: 64%

“…Single Immunohistochemistry Staining. Immunohistochemistry was performed as previously described [24] . Sections were blocked with 20% normal horse serum in PBS for 1 h followed by incubation with rabbit polyclonal antibody solutions against BDNF (1: 1,000 in 0.3% Triton X-100 containing 0.02% sodium azide in 2 !…”

Section: Colorectal Distentionmentioning

confidence: 99%

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

et al. 2009

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“…28 Neonatal MS induced long-term changes in neuroendocrine and neuropeptide secretion may also contribute to visceral hyperalgesia. Corticotrophin releasing factor 29 and nerve growth factor 30 were proved to be relevant to the neonatal MS-induced visceral hyperalgesia. In the past few years, the underlying relationship between gut microbiota and functional gastrointestinal disorders has attracted more attention.…”

Section: Discussionmentioning

confidence: 99%

Maternal Separation Induced Visceral Hypersensitivity from Childhood to Adulthood

Zhang

Sun

et al. 2017

J Neurogastroenterol Motil

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Background/AimsEarly adverse life events (EALs) are relevant to irritable bowel syndrome in adulthood. Maternal separation (MS), as one of the EALs, has proved to induce visceral hypersensitivity in adult rats. However, the effect of MS on visceral hypersensitvity from the post-weaning period to adulthood remains unknown. MethodsOne hundred and ten neonatal Sprague-Dawley rats were randomly divided into 2 groups: rats in the MS group were exposed to 3 hours daily MS on postnatal day (PND) 2-14; the normal control (NC) group remained undisturbed. Visceral sensitivity was determined by measuring the visceromotor response to colorectal distention on PND21, 35, and 56. Anxiety-like behaviors were measured by the open field test. ResultsCompared with NC rats, MS rats showed significant visceral hypersensitivity from the post-weaning period to adult. The proportion of visceral hypersensitive rats decreased with age from 87.5% to 70.0% in the female MS group and from 90.0% to 66.7% in the male MS group. The relative VMR ratio of MS and NC on PND21 was higher than PND35 and PND56. MS rats showed decreased ability of movement and exploration to the novel environment in the post-weaning period, obesity in the prepubertal period, and more anxietylike behaviors in adulthood. ConclusionsMS can significantly affect visceral sensitivity and behaviors of rats in different age stages, especially in the post-weaning period. Visceral hypersensitivity of MS rats is more pronounced in the post-weaning period and slightly restored in adults. Thus, visceral hypersensitivity in the post-weaning period might play a more meaningful pathophysiologic role in the formation of adult irritable bowel syndrome.

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“…The source of TrkA immunoreactivity in the superficial dorsal horn is represented by the terminals of unmyelinated polymodal C fibres coming from the ganglion and terminating in the upper laminae of the dorsal horn [40]. The incoming fibres did not show substantial variation in TrkA immunoreactivity, indicating that the decrease in immunoreactivity was selectively confined to the synaptic circuitry in the dorsal horn and suggesting that it was directly related to in situ downregulation of TrkA protein and not to a loss of incoming TrkA positive fibres.…”

Section: Discussionmentioning

confidence: 99%

Electroacupuncture counteracts the development of thermal hyperalgesia and the alteration of nerve growth factor and sensory neuromodulators induced by streptozotocin in adult rats

2011

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Aims/hypothesis Diabetes is considered the leading cause of neuropathies in developed countries. Dysfunction of nerve growth factor (NGF) production and/or utilisation may lead to the establishment of diabetic neuropathies. Electroacupuncture has been proved effective in the treatment of human neuropathic pain as well as in modulating NGF production/activity. We aimed at using electroacupuncture to correct the development of thermal hyperalgesia and the tissue alteration of NGF and sensory neuromodulators in a rat model of type 1 diabetes. Methods Adult rats were injected with streptozotocin to induce diabetes and subsequently treated with lowfrequency electroacupuncture for 3 weeks. Variation in thermal sensitivity was studied during the experimental course. Hindpaw skin and spinal cord protein content of NGF, NGF receptor tyrosine kinase A (TrkA), substance P (SP), transient receptor potential vanilloid 1 (TRPV1) receptor and glutamic acid decarboxylase-67 (GAD-67) were measured after electroacupuncture treatments. The skin and spinal cord cellular distribution of TrkA was analysed to explore NGF signalling. Results Early after streptozotocin treatment, thermal hyperalgesia developed that was corrected by electroacupuncture. The parallel increases in NGF and TrkA in the spinal cord were counteracted by electroacupuncture. Streptozotocin also induced variation in skin/spinal TrkA phosphorylation, increases in skin SP and spinal TRPV1 and a decrease in spinal GAD-67. These changes were counteracted by electroacupuncture. Conclusions/interpretation Our results point to the potential of electroacupuncture as a supportive therapy for the treatment of diabetic neuropathies. The efficacy of electroacupuncture might depend on its actions on spinal/peripheral NGF synthesis/utilisation and normalisation of the levels of several sensory neuromodulators.

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Visceral hyperalgesia induced by neonatal maternal separation is associated with nerve growth factor–mediated central neuronal plasticity in rat spinal cord

Cited by 47 publications

References 50 publications

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

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

Maternal Separation Induced Visceral Hypersensitivity from Childhood to Adulthood

Electroacupuncture counteracts the development of thermal hyperalgesia and the alteration of nerve growth factor and sensory neuromodulators induced by streptozotocin in adult rats

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