Pharmacological mechanisms of locus coeruleus activation -recruitment of descending inhibition for treatment of neuropathic pain-

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Pregabalin and gabapentin are often used as first-line drugs in the treatment of neuropathic pain. Previous studies suggest that these drugs activate descending inhibitory systems. In the present project, using rats, we observed that systemic administration of pregabalin increased noradrenaline level in the dorsal horn of the lumbar spinal cord through activation of locus coeruleus. The increased noradrenaline inhibit not only neuropathic pain but also acute pain via spinal alpha-2 adrenoceptors. The mechanisms by which pregabalin activates locus coeruleus are still under active investigation.