Brain research bulletin
-
Brain research bulletin · Jul 2013
Pronociceptive changes in the activity of rostroventromedial medulla (RVM) pain modulatory cells in the streptozotocin-diabetic rat.
Neuropathic pain is one of the most frequent complications of diabetes. The increased neuronal activity of primary afferents and spinal cord neurons in streptozotocin (STZ)-diabetic rats increases the recruitment of the nociceptive ascending pathways, which may affect the activity of pain control circuits in the brain. This study aimed to characterize the electrophysiological responses of neurons of the rostroventromedial medulla (RVM), a key brainstem area involved in descending modulation of nociceptive neurotransmission at the spinal cord, in STZ-diabetic rats. ⋯ On the contrary, the number of active antinociceptive OFF-like cells was significantly lower in the STZ-diabetic rats and their spontaneous activity was decreased when compared with CTRL. Overall, the changes in the activity of RVM pain modulatory cells in STZ-diabetic rats point to enhancement of descending pain facilitation. Based on similar results obtained at the RVM in traumatic neuropathic pain models, the changes in the electrophysiological responses of RVM in STZ-diabetic rats may account for exacerbated pain-like behaviors in diabetic neuropathy.
-
Brain research bulletin · Jun 2013
Spinal CCL2 and microglial activation are involved in paclitaxel-evoked cold hyperalgesia.
The antineoplastic paclitaxel induces a sensory neuropathy that involves the spinal release of neuroinflammatory mediators and activation of glial cells. Although the chemokine CCL2 can evoke glial activation and its participation in neuropathic pain has been demonstrated in other models, its involvement in paclitaxel-evoked neuropathy has not been previously explored. Paclitaxel-evoked cold hypernociception was assessed in mice by the unilateral cold plate test and the effects on cold hyperalgesia of the CCR2 antagonist RS 504393, the CCR1 antagonist J113863, the microglial inhibitor minocycline or an anti-CCL2 antibody were tested. ⋯ Besides, the implication of microglial activation is supported by the increase in the immunolabelling of Iba-1, but not GFAP, in the spinal cord of paclitaxel-treated mice and by the inhibition of cold hyperalgesia produced by the i.t. administration of the microglial inhibitor minocycline (1-10 nmol). Finally, the neutralization of spinal CCL2 by the i.t. administration of a selective antibody for 3 days almost totally inhibited paclitaxel-evoked microglial activation. In conclusion, our results indicate that paclitaxel-evoked cold hypernociception depends on the activation of CCR2 due to the spinal release of CCL2 and the subsequent microglial activation.
-
Brain research bulletin · May 2013
Long-term effects of selective immunolesions of cholinergic neurons of the nucleus basalis magnocellularis on the ascending cholinergic pathways in the rat: a model for Alzheimer's disease.
Alzheimer's disease is associated with a significant decrease in the cholinergic input to the neocortex. In a rat model of this depletion, we analyzed the subsequent long-term changes in cholinergic fiber density in two well-defined areas of the frontal and parietal cortices: Fr1, the primary motor cortex, and HL, the hindlimb area of the somatosensory (parietal) cortex, two cortical cholinergic fields that receive inputs from the nucleus basalis magnocellularis (nBM). A specific cholinergic lesion was induced by the intraparenchymal injection of 192 IgG-saporin into the nBM. ⋯ The cholinergic fiber densities in cortical areas Fr1 and HL remained similarly decreased (to 62% and 68% of the control values, respectively) up to 20 weeks. No significant rebound in AChE activity occurred either in the nBM or in the cortices during the period investigated. This study therefore demonstrated that, similarly to the very extensive reduction in the number of ChAT-positive neurons in the nBM, cortical areas Fr1 and HL underwent long-lasting reductions in the number of AChE-positive fibers in response to specific cholinergic lesioning of the nBM.
-
Brain research bulletin · Apr 2013
ReviewExtrasynaptic AMPA receptors in the dorsal horn: evidence and functional significance.
Extrasynaptic AMPA receptors (AMPARs) are widely expressed in the brain, spinal cord and periphery. These receptors are critically involved in activity-dependent synaptic transmission and changes in their functioning are causally linked to multiple neuropathologies in the central nervous system (CNS). ⋯ In addition, we summarize current knowledge about the role of extrasynaptic AMPARs in the development and maintenance of pain states during inflammation. This knowledge potentially suggests the development of alternative therapies to prevent and/or treat inflammatory pain.
-
Brain research bulletin · Apr 2013
The role of glutamate release mediated by extrasynaptic P2X7 receptors in animal models of neuropathic pain.
Purinergic signaling represents a major non-synaptic signaling mechanism in the normal and pathological nervous system. The expression of the purinergic ligand gated ion channel P2X7 receptor (P2rx7) has been described on nerve terminals as well as in non-neuronal cells, such as astrocytes and microglia. The activation of P2rx7s results in Ca(2+) influx and increased transmitter release in the brain. ⋯ The results suggest that activation of P2rx7 by ATP releases glutamate in the spinal cord, which might contribute to mechanical allodynia following PNL. On the other hand, this release does not contribute to glutamate efflux evoked by conventional neuronal activity, which is consistent with the idea that P2X7 receptors are either extrasynaptic or expressed on non-neuronal cells. This article is part of a Special Issue entitled 'Extrasynaptic ionotropic receptors'.