Neuroscience
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Neonatal maternal separation (NMS) has been shown to trigger alterations in neuroendocrine, neurochemical and sensory response to nociceptive stimuli along the brain-gut axis. These alterations may be the result of a cascade of events that are regulated by neurotrophic factors. Nerve growth factor (NGF), a member of the neurotrophin family, is essential for the development and maintenance of sensory neurons and for the formation of central pain circuitry. ⋯ Quantitative analysis of TrkA-ir neurons indicated a significant interactive effect of NMS and CRD on the mean number of TrkA-ir neurons in laminae V-VI of rats, in which significant difference was found between NMS+CRD and NH+CRD. Double immunofluorescence of TrkA and Fos showed that CRD has a significant effect on TrkA expression in Fos-positive neurons in laminae V-VI and lamina X of rats, while no significant difference was found between NMS+CRD and NH+CRD. These results demonstrate that NMS induced alterations in NGF protein level and TrkA expression in adult rat spinal cord and indicate that NGF is a crucial mediator for the changes in neuronal plasticity that occur in NMS-induced visceral hyperalgesia.
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Craniofacial muscle pain including muscular temporomandibular disorders accounts for a substantial portion of all pain perceived in the head and neck region. In spite of its high clinical prevalence, the mechanisms of chronic craniofacial muscle pain are not well understood. Injection of acidic saline into rodent hindlimb muscles produces pathologies which resemble muscular pathologies in chronic pain patients. ⋯ Although pH may alter CGRP release in primary afferent neurons, the number of CGRP-muscle afferent neurons did not change following i.m. injection of acidic saline. Further, there was no change in ganglionic iCGRP levels at 1, 4 or 12 days after i.m. injection of acidic saline. While these findings extend our earlier reports that CFA-induced muscle inflammation results in behavioral and neuropeptide changes they further suggest that i.m. acidification in craniofacial muscle evokes different responses than in hindlimb muscle and imply that disparate proton sensing mechanisms underlie these discrepancies.
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Recent findings demonstrate that chemokines, and more specifically CC chemokine ligand 2 (CCL2 or monocyte chemoattractant protein-1), play a major role in pain processing. In the present study, we assess nociceptive responses of mice that overexpressed CCL2 under control of glial fibrillary acidic protein promoter (CCL2 tg). In models of acute nociception CCL2 tg mice demonstrated significantly enhanced nociceptive behavior relative to wild-type controls in responses to both thermal (hot plate) and chemical (formalin test) stimulus modalities. ⋯ Parallel to these enhanced behavioral responses CCL2 serum levels were significantly greater in CCL2 overexpressing mice and remained elevated 7 days post CFA. Consequently, proinflammatory cytokine mRNA expression (IL-1beta, IL-6, and TNFalpha) levels were greater in skin, dorsal root ganglia (DRG), and spinal cord, whereas the anti-inflammatory cytokine (IL-10) level was lower in skin and DRG in CCL2 overexpressing mice than in control mice. Taken together with data from CCR2-deficient mice, these present data confirm a key role of CCL2/CCR2 axis in pain pathways and suggest that inhibiting this axis may result in novel pain therapies.
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Sensorineural hearing loss (SNHL) comprises hearing disorders with diverse pathologies of the inner ear and the auditory nerve. To date, an unambiguous phenotypical characterization of the specific pathologies in an affected individual remains impossible. Here, we evaluated the use of scalp-recorded auditory steady-state responses (ASSR) and transient auditory brainstem responses (ABR) for differentiating the disease mechanisms underlying sensorineural hearing loss in well-characterized mouse models. ⋯ Mice with defective amplification displayed a steep rise of ASSR and ABR amplitudes with increasing sound intensity, presumably reflecting a strong recruitment of synchronously activated neural elements beyond threshold. In contrast, the amplitudes of ASSR and ABR responses of mice with impaired synaptic transmission grew very little with sound intensity. In summary, ASSR allow for a rapid, objective and frequency-specific hearing assessment and together with ABR and otoacoustic emissions can contribute to the differential diagnosis of SNHL.
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Epileptiform activity induces long term aberrations in hippocampal network functions. This study was conducted in pentylenetetrazol (PTZ) -kindled rats to examine offsetting of aberrations associated with seizure proneness in hippocampus area CA1 by theta pulse stimulation (TPS: 5 Hz trains for 3 min) -induced activity pattern. In hippocampal slices from both control and kindled rats, the field excitatory postsynaptic potentials (fEPSP) and population spikes (PS) were simultaneously recorded through electrodes in the apical dendrites and stratum pyramidale, respectively. ⋯ The lasting depressive effect of TPS on the PS amplitude was converted into facilitation by adenosine A1 receptor antagonist 8-cyclopentyl-1, 3-dipropylxanthine (CPX). Potentiation of the PS amplitude by TPS in the presence of CPX was blocked by an N-methyl-d-aspartate receptor antagonist AP5. We hypothesize that the extracellular adenosine spillover, acting through adenosine A1 receptors, during TPS-induced activity pattern could trigger a homeostatic process for correcting network imbalances caused by epileptiform activity.