Extracellular signal-regulated kinase activation in the chronic constriction injury model of neuropathic pain in anaesthetized rats.
BACKGROUND
The role of extracellular signal-regulated kinases (ERKs) in nociception has been explored in the last years. While in spinal cord their activation is frequently correlated with pain or acute noxious stimuli, supraspinally, this association is not so evident and remains unclear. This study aims to evaluate ERK1/2 activation in the spinal cord and brainstem nuclei upon neuropathy and/or an additional mechanical stimulus.


METHODS
Acute noxious mechanical stimulation was applied in the left hindpaw of anaesthetized SHAM-operated and chronic constriction injured (CCI, neuropathic pain model) rats. Other SHAM or CCI rats did not receive any stimulus. Immunohistochemistry against the phosphorylated isoforms of ERK1/2 (pERK1/2) was performed in lumbar spinal cord and brainstem sections to assess ERK1/2 activation.


RESULTS
In the spinal cord, stimulation promoted an increase in pERK1/2 expression in the superficial dorsal horn of SHAM rats. No significant effects were caused by CCI alone. At supraspinal level, changes in ERK1/2 activation induced by CCI were observed in A5, locus coeruleus (LC), raphe obscurus (ROb), raphe magnus, dorsal raphe (DRN), lateral reticular and paragigantocellularis nucleus. CCI increased pERK1/2 expression in all these nuclei, with exception of LC, where a significant decrease was verified. Mechanical noxious stimulation of CCI rats decreased pERK1/2 expression in ROb and DRN, but no further changes were detected in either SHAM- or CCI-stimulated animals.


CONCLUSIONS
ERK1/2 are differentially activated in the spinal cord and in selected brainstem nuclei implicated in nociception, in response to an acute noxious stimulus and/or to a neuropathic pain condition.
Departamento de Biologia Experimental, Centro de Investigação Médica-Faculdade de Medicina (CIM-FMUP), Universidade do Porto, Porto, Portugal.
G S
GS
Borges
E
E
Berrocoso
A
A
Ortega-Alvaro
J A
JA
Mico
F L
FL
Neto
D059787:Acute Pain / Q000378:metabolism*; D000758:Anesthesia; D000818:Animals; D001933:Brain Stem / Q000201:enzymology; D059350:Chronic Pain / Q000378:metabolism*; D004195:Disease Models, Animal; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009437:Neuralgia / Q000378:metabolism*; D009619:Nociceptors / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000378:metabolism; D013116:Spinal Cord / Q000201:enzymology
C535149:Mapk1 protein, rat; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3