Perineural clonidine reduces p38 mitogen-activated protein kinase activation in sensory neurons.
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.
Liu
Baogang
B
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.
Eisenach
James C
JC
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*
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