title: Perineural clonidine reduces p38 mitogen-activated protein kinase activation in sensory neurons.
abstract: Perineural injection of clonidine at the site of nerve injury reduces hypersensitivity while simultaneously reducing leukocyte number and cytokine expression and hyperexcitability in sensory neurons. The activation of p38 mitogen-activated protein kinase in sensory neurons contributes to the development and maintenance of inflammatory and neuropathic pain. Here, we tested whether perineural clonidine affected activation of p38 mitogen-activated protein kinase following partial sciatic nerve ligation. Perineural clonidine significantly increased withdrawal threshold and concomitantly reduced phosphorylation of p38 mitogen-activated protein kinase in sensory neurons ipsilateral to injury. Clonidine's effects were blocked by the alpha2-adrenoceptor antagonist, BRL44408. These data suggest that activation of alpha2-adrenoceptors at the site of nerve injury, probably by immune modulation, reduces intracellular signaling in primary afferents that leads to hypersensitivity.
authors.affiliation: Department of Anesthesiology, Center for the Study of Pharmacologic Plasticity in the Presence of Pain, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
authors.forename: Baogang
authors.initials: B
authors.lastname: Liu
authors.forename: James C
authors.initials: JC
authors.lastname: Eisenach
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal; D002452:Cell Count / Q000379:methods; D003000:Clonidine / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007150:Immunohistochemistry / Q000379:methods; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D009475:Neurons, Afferent / Q000187:drug effects* / Q000201:enzymology*; D010147:Pain Measurement; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D020426:Sciatic Neuropathy / Q000473:pathology; D012684:Sensory Thresholds / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D007211:Indoles; D054833:Isoindoles; D048051:p38 Mitogen-Activated Protein Kinases; D003000:Clonidine; C072125:BRL 44408