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, originating in damaged nerve and not peripheral nociceptors, is often resistant to treatment by opiates given by the oral, parenteral or spinal routes. This failure to obtain satisfactory pain relief is generally ascribed to psychological factors or to individual peculiarities in drug metabolism or kinetics. Currently, psychotropic and antidepressant drugs are among the first choices in treating painful conditions due to partial nerve lesions. We present a 56-year-old man who suffered intractable pain confined to his left knee following emergency L2-3 vertebral decompression, after collapse due to metastatic disease. 12 mg of morphine and 10 of diazepam given together intravenously did not lessen pain. Acute, solitary spinal nerve root injury was hypothesized. 2 mg of haloperidol injected IV gave complete relief of pain without hypotension or deep sedation. There is no definite explanation for the resistance of neuropathic pain to opiates.
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PMID:[Neuropathic pain unrelieved by morphine, alleviated by haloperidol]. 235 28

Neuropathic pain that occurs after peripheral nerve injury depends on the hyperexcitability of neurons in the dorsal horn of the spinal cord. Spinal microglia stimulated by ATP contribute to tactile allodynia, a highly debilitating symptom of pain induced by nerve injury. Signalling between microglia and neurons is therefore an essential link in neuropathic pain transmission, but how this signalling occurs is unknown. Here we show that ATP-stimulated microglia cause a depolarizing shift in the anion reversal potential (E(anion)) in spinal lamina I neurons. This shift inverts the polarity of currents activated by GABA (gamma-amino butyric acid), as has been shown to occur after peripheral nerve injury. Applying brain-derived neurotrophic factor (BDNF) mimics the alteration in E(anion). Blocking signalling between BDNF and the receptor TrkB reverses the allodynia and the E(anion) shift that follows both nerve injury and administration of ATP-stimulated microglia. ATP stimulation evokes the release of BDNF from microglia. Preventing BDNF release from microglia by pretreating them with interfering RNA directed against BDNF before ATP stimulation also inhibits the effects of these cells on the withdrawal threshold and E(anion). Our results show that ATP-stimulated microglia signal to lamina I neurons, causing a collapse of their transmembrane anion gradient, and that BDNF is a crucial signalling molecule between microglia and neurons. Blocking this microglia-neuron signalling pathway may represent a therapeutic strategy for treating neuropathic pain.
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PMID:BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. 1635