Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0423716 (Neuropathic pain)
 1,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropathic pain is a common clinical problem with complex aetiology, mechanisms and symptoms. Alterations in spinal gamma-aminobutyric acid (GABA) receptors may contribute to persistent pain states. The aim of the present study is to investigate potential changes of spinal GABA(A)-receptor function following peripheral nerve injury. Effects of spinal administration of the GABA(A)-receptor agonist muscimol (0.1-30 microg/50 microl) on electrically-evoked responses of spinal neurones in control, spinal nerve ligated and sham operated halothane-anaesthetised rats were studied. Spinal muscimol significantly (10 microg/50 microl) reduced evoked Abeta-, Adelta- and C-fibre responses of spinal neurones in control rats (58+/-22% of control, P<0.05; 3+/-2% of control, P<0.001; and 8+/-7% of control, P<0.001; respectively). Muscimol produced significantly greater inhibition of Adelta- and C-fibre evoked neuronal responses compared to Abeta-fibre evoked neuronal responses in control rats (P<0.001). C-fibre mediated post-discharge responses and the non-potentiated C-fibre evoked responses were significantly inhibited by muscimol in control rats. Inhibitory effects of muscimol (10 microg/50 microl) were blocked by pre-application of spinal bicuculline (10 microg/50 microl). Following either sham surgery, or spinal nerve ligation, spinal muscimol inhibited Abeta-, Adelta- and C-fibre evoked responses of spinal neurones to a similar extent, however significant inhibitory effects on the post-discharge response were not observed in nerve injured rats. Our data demonstrate that GABA(A)-receptor control of Abeta- and Adelta-fibre evoked responses are not altered in nerve injured or sham operated rats, compared to control. However, following nerve injury we report a reduction in GABA(A)-receptor control of C-fibre responses, in particular in relation to post-discharge responses.
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PMID:Effects of spinal administration of muscimol on C- and A-fibre evoked neuronal responses of spinal dorsal horn neurones in control and nerve injured rats. 1254 72

Neuropathic pain (NPP) due to sensory nerve injury is, in part, the result of peripheral sensitization leading to a long-lasting increase in synaptic plasticity in the spinal dorsal horn. Thus, activation of GABA-mediated inhibitory inputs from sensory neurons could be beneficial in the alleviation of NPP symptoms. Dorsal root ganglia (DRG) conduct painful stimulation from the periphery to the spinal cord. Long-lasting down-regulation in GABA tone or sensitivity in DRG neurons has been reported in animals with neuropathy. To determine the function of GABA in DRG in the development of NPP, we examined how the acute pharmacological GABA(A)-receptor modulation of L5 DRG in vivo affects the development of NPP in rats with crush injury to the sciatic nerve. Direct application of muscimol and gaboxadol, GABA(A) agonists, to L5 DRG immediately after injury induced dose-dependent alleviation, whereas bicuculline and picrotoxin, GABA(A) antagonists, worsened NPP postaxonal injury. The pain-alleviating effects of muscimol and gaboxadol were blocked by bicuculline. Muscimol, applied at the time of injury, caused complete and long-lasting abolishment of NPP development. However, when muscimol was applied after NPP had already developed, its pain-alleviating effect, although significant, was short-lived. Using a fluorescent tracer, sodium fluorescein, we confirmed that local DRG application results in minimal spread into the corresponding dorsal horn of the ipsilateral spinal cord. GABA(A) receptors in DRG are important in the development of NPP after peripheral nerve injury, making timely exogenous GABAergic manipulation at the DRG level a potentially useful therapeutic modality.
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PMID:GABAA receptor modulation in dorsal root ganglia in vivo affects chronic pain after nerve injury. 1855 16