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 resulting from peripheral nerve injury can often be relieved by administration of alpha-adrenergic receptor antagonists. Tonic activation of alpha-adrenergic receptors may therefore facilitate the hyperalgesia and allodynia associated with neuropathic pain. It is currently unclear whether alpha2A- or alpha2c-adrenergic receptor subtypes are involved in the pro-nociceptive actions of alpha-adrenergic receptors under neuropathic conditions. We therefore investigated the effects of peripheral nerve injury on the expression of these subtypes in rat spinal cord using immunohistochemical techniques. In addition, neuropeptide Y immunoreactivity was examined as an internal control because it has previously been shown to be up-regulated following nerve injury. We observed a decrease in alpha2A-adrenergic receptor immunoreactivity in the spinal cord ipsilateral to three models of neuropathic pain: complete sciatic nerve transection, chronic constriction injury of the sciatic nerve and L5/L6 spinal nerve ligation. The extent of this down-regulation was significantly correlated with the magnitude of injury-induced changes in mechanical sensitivity. In contrast, alpha2c-adrenergic receptor immunoreactivity was only increased in the spinal nerve ligation model; these increases did not correlate with changes in mechanical sensitivity. Neuropeptide Y immunoreactivity was up-regulated in all models examined. Increased expression of neuropeptide Y correlated with changes in mechanical sensitivity. The decrease in alpha2A-adrenergic receptor immunoreactivity and the lack of consistent changes in alpha2C-adrenergic receptor immunoreactivity suggest that neither of these receptor subtypes is likely to be responsible for the abnormal adrenergic sensitivity observed following nerve injury. On the contrary, the decrease in alpha2A-adrenergic receptor immunoreactivity following nerve injury may result in an attenuation of the influence of descending inhibitory noradrenergic input into the spinal cord resulting in increased excitatory transmitter release following peripheral stimuli.
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PMID:Effects of peripheral nerve injury on alpha-2A and alpha-2C adrenergic receptor immunoreactivity in the rat spinal cord. 1050 65

Neuropeptide Y (NPY) is believed to exert antinociceptive actions by inhibiting the release of substance P and other 'pain neurotransmitters' in the spinal cord dorsal horn. However, the physiological significance and potential therapeutic value of NPY remain obscure. It is also unclear which receptor subtype(s) are involved. To identify a possible physiological role for the NPY Y1 receptor in pain transmission, we generated NPY Y1 receptor null mutant (Y1-/-) mice by homologous recombination techniques. Here we show that Y1-/- mice develop hyperalgesia to acute thermal, cutaneous and visceral chemical pain, and exhibit mechanical hypersensitivity. Neuropathic pain is increased, and the mice show a complete absence of the pharmacological analgesic effects of NPY. In the periphery, Y1 receptor activation is sufficient and required for substance P release and the subsequent development of neurogenic inflammation and plasma leakage. We conclude that the Y1 receptor is required for central physiological and pharmacological NPY-induced analgesia and that its activation is both sufficient and required for the release of substance P and initiation of neurogenic inflammation.
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PMID:Reduced antinociception and plasma extravasation in mice lacking a neuropeptide Y receptor. 1120 47