Use of differential normal pulse voltammetry for the measurement of locus coeruleus catecholaminergic metabolism in an acute anaesthetized rodent model of allodynia: effect of mexiletine.
Neuropathic pain can be triggered by non-painful stimuli (e.g., light touch), a sensory abnormality termed allodynia. The acute blockade of spinal glycine receptors with intrathecal strychnine induces a reversible allodynia-like state in the rat. We describe the application of in vivo differential normal pulse voltammetry with carbon fibre micro-electrodes for monitoring the catechol oxidation current (CAOC) of the locus coeruleus (LC) in the strychnine model of allodynia. In addition, we tested the effect of mexiletine, a drug useful in the management of clinical neuropathic pain in this model. Our results show that somatosensory processing in the spinal cord of urethane-anaesthetized rats is radically altered during glycine receptor blockade such that the normally innocuous stimulus of hair deflection causes the marked activation of the LC as determined using in vivo differential normal pulse voltammetry. Mexiletine suppressed the LC and cardiovascular responses of strychnine induced allodynia. Results of this study indicate that LC CAOC, an index of LC neuronal activity: (a) is a sensitive biochemical index of strychnine-allodynia; (b) is temporally correlated with the cardiovascular and motor responses evoked by hair deflection during glycine receptor blockade; and (c) can be used to quantitate allodynia in the strychnine model.
Duggan
S
S
Department of Anaesthesia, Queen's University, Kingston, ON, Canada.
Milne
B
B
Loomis
C
C
D000758:Anesthesia; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002395:Catecholamines / Q000378:metabolism*; D004567:Electrodes, Implanted; D004594:Electrophysiology; D018684:Glycine Agents / Q000494:pharmacology; D008012:Lidocaine / Q000494:pharmacology; D008125:Locus Coeruleus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008801:Mexiletine / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013331:Strychnine / Q000494:pharmacology
D000779:Anesthetics, Local; D000889:Anti-Arrhythmia Agents; D002395:Catecholamines; D018684:Glycine Agents; D008801:Mexiletine; D008012:Lidocaine; D013331:Strychnine