The European journal of neuroscience
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Comparative Study
Fractalkine (CX3CL1) and fractalkine receptor (CX3CR1) distribution in spinal cord and dorsal root ganglia under basal and neuropathic pain conditions.
Fractalkine is a unique chemokine reported to be constitutively expressed by neurons. Its only receptor, CX3CR1, is expressed by microglia. Little is known about the expression of fractalkine and CX3CR1 in spinal cord. ⋯ By contrast, CX3CR1 was expressed by microglia in the basal state, and the microglial cellular concentration was up-regulated in a regionally specific manner in response to neuropathy. CX3CR1-expressing cells were identified as microglia by their cellular morphology and positive OX-42 and CD4 immunostaining. The cellular distribution of fractalkine and CX3CR1 in the spinal circuit associated with nociceptive transmission supports a potential role in the mechanisms that contribute to the exaggerated pain state in these models of neuropathy.
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Comparative Study
Deletion of the CCK2 receptor gene reduces mechanical sensitivity and abolishes the development of hyperalgesia in mononeuropathic mice.
Previous studies suggest that cholecystokinin (CCK) is implicated in the modulation of pain sensitivity and the development of neuropathic pain. We used CCK(2) receptor deficient (CCK(2) (-/-)) mice and assessed their mechanical sensitivity using Von Frey filaments, as well as the development and time course of mechanical hyperalgesia in a model of neuropathic pain. We found that CCK(2) (-/-) mice displayed mechanical hyposensitivity, which was reversed to the level of wild-type animals after administration of naloxone (0.1-10 mg/kg). ⋯ In addition, induction of neuropathy resulted in further increase of opioid delta receptor in CCK(2) (-/-) mice. Gene expression results indicate up-regulation of opioid system in CCK(2) (-/-) mice, which apparently result in decreased neuropathy score. Our study suggests that not only pain sensitivity, but also mechanical sensitivity and the development of neuropathic pain are regulated by antagonistic interactions between CCK and opioid systems.
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Comparative Study
Dual effects of gabapentin and pregabalin on glutamate release at rat entorhinal synapses in vitro.
We have recently shown that the anticonvulsant drugs phenytoin, lamotrigine and sodium valproate all reduce the release of glutamate at synapses in the entorhinal cortex in vitro. In the present investigation we determined whether this property was shared by gabapentin and pregabalin, using whole-cell patch-clamp recordings of excitatory postsynaptic currents (EPSCs) in layer V neurons in slices of rat entorhinal cortex. Both drugs reduced the amplitude and increased the paired-pulse ratio of EPSCs evoked by electrical stimulation of afferent inputs, suggesting a presynaptic effect to reduce glutamate release. ⋯ The reduction in frequency induced by gabapentin or pregabalin was blocked by application of the l-amino acid transporter substrate l-isoleucine. The results show that gabapentin and pregabalin, like other anticonvulsants, reduce glutamate release at cortical synapses. It is possible that this reduction is a combination of two effects: a reduction of activity-dependent release possibly via interaction with P/Q-type voltage-gated Ca channels, and a second action, as yet unidentified, occurring downstream of Ca influx into the presynaptic terminals.