The European journal of neuroscience
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Comparative Study
Downregulation of P2X3 receptor-dependent sensory functions in A/J inbred mouse strain.
There is large variability in the various pain responses including those to tissue injury among inbred mouse strains. However, the determinant factors for the strain-specific differences remain unknown. The P2X3 sensory-specific ATP-gated channel has been implicated as a damage-sensing molecule that evokes a pain sensation by receiving endogenous ATP from injured tissue. ⋯ In A/J DRG neurons the P2X3 protein level was significantly lower compared with C57BL/6 J DRG neurons. The change in P2X3 protein was selective because P2X2 protein was expressed equally in both strains. The present study suggests that the downregulation of sensory P2X3 could be one of the molecular predispositions to low sensitivity to tissue injury pain in the A/J inbred mouse strain.
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Fractalkine is a neuronally expressed chemokine that acts through its G-protein-coupled receptor CX3CR1, localized on microglial and immune cells. Fractalkine might be involved in neuroinflammatory processes secondary to neuronal damage, which normally occur in a time frame of days after ischaemia. We evaluated by in situ hybridization and immunohistochemistry the expression of fractalkine and CX3CR1 in the rat brain, after a transient occlusion of the middle cerebral artery. ⋯ Fractalkine synthesis was also induced in endothelial cells of the infarcted area, at 48 h and 7 days after ischaemia. CX3CR1 expression was detected in the activated microglial cells of the ischaemic tissue 24 and 48 h after ischaemia, and became strongly up-regulated in macrophages/phagocytic microglia inside the infarcted tissue 7 days after ischaemia. These data suggest that fractalkine may participate in the activation and chemoattraction of microglia into the infarcted tissue, and contribute to the control of leucocyte trafficking from blood vessels into the injured area.
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Considerable debate persists concerning peripheral vs. central mechanisms underlying the second phase of the nociceptive response in the formalin test in the rat. To gain insight into the neurophysiological basis of this pain, we investigated the effects of block of afferent nerve conduction during the second phase of formalin-evoked excitation of single nociceptive neurons recorded extracellularly from rat spinal dorsal horn segments (L(3-4)) in pentobarbital-anaesthetized, male Sprague-Dawley rats. Rats were spinally transected (T(9)) to examine exclusively peripheral and spinal nociceptive processing. ⋯ It is concluded that: (i) spinal mechanisms alone are not sufficient for induction and maintenance of second phase increased discharge of spinal nociceptive dorsal horn neurons; (ii) descending influences via supraspinal inputs are not causal in the development and maintenance of second phase increased discharge and (iii) tonic input from afferent neurons during the second phase plays a primary and essential role in generating and sustaining the second phase of elevated discharge of dorsal horn neurons and, thus, presumably the second phase of nociceptive scores in the formalin test. The data in this study reveal how much of an altered synaptically elicited response in the spinal dorsal horn can be attributed to postsynaptic plastic changes vs. how much can be simply due to increased synaptic input. The present results are important not only in the context of the formalin test but also in the context of other models related to inflammatory pain and neuropathic pain.