Neuroscience letters
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Neuroscience letters · May 1998
Effect of spinal cord stimulation on tactile hypersensitivity in mononeuropathic rats is potentiated by simultaneous GABA(B) and adenosine receptor activation.
In rats with abnormally low withdrawal thresholds ('allodynia') in one hindpaw induced by a photochemical sciatic lesion, an intrathecal catheter was inserted to the lumber enlargement and an epidural electrode was implanted at T11. I.t. administration of GABA(B) or adenosine A1 receptor agonists (baclofen, R(-)-N6-(2-phenylisopropyl)adenosine (R-PIA)) suppressed allodynia in a dose-dependent fashion. ⋯ In SCS responding rats, combination of a selective GABA(B) and an adenosine A1 receptor antagonist (CGP 55845, CPT) in low, ineffective doses abolished the SCS-induced threshold normalization. These results indicate that GABAergic and adenosine-dependent mechanisms are involved in the SCS effect and further suggest a strategy for enhancing the therapeutic efficacy of SCS.
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Neuroscience letters · May 1998
Motor denervation induces altered muscle fibre type densities and atrophy in a rat model of neuropathic pain.
Loose ligation of a sciatic nerve in rats (chronic constriction injury; CCI) provokes sensory, autonomic, and motor disturbances like those observed in humans with partial peripheral nerve injury. So far, it is unknown whether these motor disturbances result from (mechanical) allodynia or from damage to the motor neuron. These considerations prompted us to assess, in CCI rats, the density of motor axons in both the ligated sciatic nerve and the ipsilateral femoral nerve. ⋯ In line with these findings, we observed altered fibre type densities in muscle tissue innervated by the ligated sciatic nerve as well as the non-ligated femoral nerve indicative of motor denervation rather than hypokinesia. The findings of this study suggest that the motor disorder induced by partial nerve injury involves degeneration of motor nerve fibres not only within the primarily affected nerve but also within adjacent large peripheral nerves. This spread outside the territory of the primarily affected nerve suggests degeneration of motor neurons at the level of the central nervous system.
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Neuroscience letters · Mar 1998
Amount of sympathetic sprouting in the dorsal root ganglia is not correlated to the level of sympathetic dependence of neuropathic pain in a rat model.
Incomplete peripheral nerve injury often leads to neuropathic pains, some of which are relieved by sympathectomy, and results in sympathetic postganglionic nerve fiber sprouting in the dorsal root ganglion (DRG). This study was performed to see whether the sprouting in the DRG plays a key role in the sympathetic dependence of neuropathic pain. ⋯ Immuno-histochemical staining with tyrosine hydroxylase antibody of the S1-S3 DRGs was not correlated with the sensitivity to phentolamine. These results suggest that the degree of sympathetic dependence of neuropathic pain is not a function of the extent of the sympathetic postganglionic nerve fiber sprouting in the DRG.
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Neuroscience letters · Feb 1998
Mitogenic signaling from P1 and P2 purinergic receptors to mitogen-activated protein kinase in human fetal astrocyte cultures.
To investigate potential trophic actions of extracellular ATP in human astrocytes, we have examined mitogenic signaling by purinergic receptors in cultures prepared from first trimester rostral central nervous system tissue. We found that ATP and ATPgammaS, a hydrolysis-resistant analog, stimulated DNA synthesis, thereby indicating that P2 purinergic receptors can stimulate mitogenic signaling in these cells. In addition, ATP activated a mitogen-activated protein kinase (MAPK) termed ERK (extracellular signal-regulated protein kinase), a key component of signal transduction pathways involved in cellular proliferation and differentiation. ⋯ A selective inhibitor of protein kinase C, Ro 31-8220, blocked the ability of ATP and adenosine analogs to stimulate MAPK, thereby indicating that protein kinase C is upstream of MAPK in both P2- and P1-receptor signaling pathways. An inhibitor of the MAPK activator MEK, PD 098059, effectively blocked ATP- and 2-chloroadenosine-induced DNA synthesis, thereby indicating that the ERK/MAPK cascade mediates mitogenic signaling by P2 and P1 purinergic receptors in human fetal astrocytes. These findings suggest a role for P1 and P2 purinergic receptors in the proliferation of human fetal astrocytes.
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Neuroscience letters · Jan 1998
Tactile allodynia, but not thermal hyperalgesia, of the hindlimbs is blocked by spinal transection in rats with nerve injury.
Spinal nerve ligation produces signs of neuropathic pain in rats. Different neuronal pathways may underlie the abnormal sensory responses to thermal and tactile stimuli. Here, the possibility that local circuitry in the spinal cord and/or spinal-supraspinal loops might be involved in tactile allodynia and thermal hyperalgesia of the hindpaws was investigated by transecting the spinal cord of sham-operated or L5/L6 nerve ligated rats. ⋯ Tail-withdrawal responses to tactile probing were very robust after spinal transection in both groups, demonstrating loss of descending inhibition. These observations suggest that thermal hyperalgesia of the paw seen after nerve injury involves both spinal and supraspinal circuits, while tactile allodynia depends on a supraspinal loop. This difference may reflect afferent inputs associated with different fiber types.