Neuroscience letters
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Neuroscience letters · Oct 2008
Oligonucleotide IMT504 reduces neuropathic pain after peripheral nerve injury.
We have recently shown that the administration of bone marrow stromal cells (MSCs) prevents the development of mechanical and thermal allodynia in animals subjected to a sciatic nerve injury. Furthermore, exogenously administered MSCs have been shown to participate in the repair and regeneration of damaged tissues in a variety of animal models. However, some limitations of this therapeutic approach, basically related to the ex vivo cell manipulation procedure, have arisen. ⋯ Animals receiving either IMT504 or MSCs immediately after injury did not develop mechanical allodynia and presented a significantly lower number of nociceptive responses to cold stimulation as compared to controls. Moreover, injury-induced allodynia was significantly reduced after IMT504 delayed treatment. Our results show that the administration of IMT504 reduces neuropathic pain-associated behaviors, suggesting that IMT504 could represent a possible therapeutic approach for the treatment of neuropathic pain.
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Neuroscience letters · Oct 2008
Upregulation of the GABA-transporter GAT-1 in the spinal cord contributes to pain behaviour in experimental neuropathy.
Sciatic nerve ligation in rats (chronic constriction injury (CCI)) induces signs and symptoms that mimic human conditions of neuropathy. The central mechanisms that have been implicated in the pathogenesis of neuropathic pain include increased neuronal excitability, possibly a consequence of decreased availability of spinal GABA. GABA availability is regulated by the presence of the GABA-transporters (GATs). ⋯ These data provide evidence for possible functional involvement of GAT-1 in the development of experimental neuropathic pain. The latter can be derived from observed analgesic effects of early treatment with NO-711, a selective GAT-1 inhibitor. The obtained insights support the clinical employment of GAT-1 inhibitors to treat neuropathic pain.
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Neuroscience letters · Oct 2008
Presynaptic large-conductance calcium-activated potassium channels control synaptic transmission in the superficial dorsal horn of the mouse.
Large-conductance calcium-activated potassium channels (BK channels) have been suggested to play a substantial role in synaptic transmission in the spinal cord dorsal horn. In the present experiments, we attempted to clarify the physiological significance of BK channels in the modulation of synaptic transmission in the superficial dorsal horn where nociceptive information is processed. Spontaneously occurring excitatory postsynaptic currents (sEPSCs) were recorded from the neurons located in the superficial dorsal horn of a mouse spinal cord slice, and the effects of iberiotoxin, a BK channel blocker, on sEPSCs were analyzed. ⋯ These findings suggest that the BK channels that are located in presynaptic terminals control synaptic transmission in the superficial dorsal horn, and that functional downregulation of BK channels accompanies the neuropathic pain induced by peripheral nerve injury. This downregulation was confirmed by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis of the BK channel alpha subunit. Taken together, our present results indicate that BK channels play crucial roles in the synaptic transmission of nociceptive information in the superficial dorsal horn.
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Sinomenine, one of the alkaloids extracted from roots or stems of Sinomenium acutum, is documented to show antinociceptive action but the action mechanism is still unclear. The present study was aimed to investigate the effect of sinomenine on opioid mu-receptor (OMR). In Chinese Hamster Ovary (CHO) cell transfected with OMR, the binding of [(3)H]naloxone was displaced by sinomenine in a concentration-dependent manner. ⋯ In a tail-flick test, sinomenine produced dose-dependent antinociception in mice, which was dose-dependently inhibited by pretreatment of naloxonazine, a selective OMR antagonist. Long-term pretreatment with sinomenine may delay the analgesic tolerance of morphine. The obtained results suggest that sinomenine has an ability to activate OMR, implicating the potential of sinomenine to be applied in clinic.
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Neuroscience letters · Oct 2008
Evidence for the involvement of the spinoparabrachial pathway, but not the spinothalamic tract or post-synaptic dorsal column, in acute bone nociception.
We have previously reported that acute noxious mechanical stimulation of bone activates neurons throughout the dorsal horn of the lumbar spinal cord, and argued that the spinal mechanisms that mediate bone nociception are different to those that mediate cutaneous and visceral nociception. In the present study, we provide evidence that the ascending spinal pathways that mediate acute bone nociception also differ to those that mediate acute cutaneous and visceral nociception. Injections of a retrograde tracer (Fluorogold) were made into the thalamus, gracile nucleus or lateral parabrachial nucleus to identify spinothalamic, post-synaptic dorsal column or spinoparabrachial projection neurons respectively (n=4 in each group). ⋯ E. M.) of the spinoparabrachial projection neurons contained Fos-like immunoreactive nuclei following bone drilling and this was significantly greater than the percentage (3.4+/-0.5%) in animals of a sham surgery group (n=4) that were not exposed to bone drilling (Mann-Whitney; p<0.05). These data provide evidence for the involvement of the spinoparabrachial pathway, but not the spinothalamic or post-synaptic dorsal column pathways, in the relay of information regarding acute noxious mechanical stimuli applied to bone, and suggest that spinal pathways that mediate acute bone nociception may be different to those that mediate acute nociception of cutaneous and visceral origin.