Activation of p-38alpha MAPK contributes to neuronal hyperexcitability in caudal regions remote from spinal cord injury.
In the present study, we examined whether activation of p-38alpha MAPK modulates mechanical allodynia and neuronal hyperexcitability, and if propentofylline (PPF, a glial modulator) modulates specifically localized activated p-38alpha MAPK expression in caudal regions remote from a low thoracic hemisection injury in rats. T13 spinal hemisection produces bilateral mechanical allodynia in hindpaws with evoked (in response to mechanical stimuli) neuronal hyperexcitability in lumbar spinal wide dynamic range (WDR) neurons compared to sham controls. The mechanical allodynia and the evoked activity of WDR neurons is attenuated by intrathecal and topical administration of SB203580, an inhibitor of p-38 MAPK activation, dose dependently (p<0.05); however, the spontaneous activity showed no significant differences compared to sham controls. After T13 spinal hemisection, significantly increased phosphorylated (activated form) p-38alpha MAPK expression was present in both superficial and deep dorsal horn neurons as well as in microglia, but not in astrocytes, in the lumbar spinal cord compared to sham controls (p<0.05). Intrathecal application of PPF significantly attenuated the expression of phosphorylated p-38alpha MAPK in superficial dorsal horn neurons (10 mM) and in microglia (1 and 10 mM) in the lumbar spinal cord compared to the hemisection group (p<0.05). In conclusion, our present data demonstrate that activated neuronal and microglial, but not astrocytic, p-38alpha MAPK contributes to the maintenance of neuronal hyperexcitability in caudal regions following spinal cord injury.
Gwak
Young S
YS
Department of Neuroscience, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1043, USA. ysgwak@utmb.edu
Unabia
Geda C
GC
Hulsebosch
Claire E
CE
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology*; D005911:Gliosis / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D006930:Hyperalgesia / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D009475:Neurons, Afferent / Q000201:enzymology / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000201:enzymology / Q000473:pathology; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D016896:Treatment Outcome; D014970:Xanthines / Q000494:pharmacology / Q000627:therapeutic use; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D018696:Neuroprotective Agents; D014970:Xanthines; C032114:propentofylline; D048051:p38 Mitogen-Activated Protein Kinases
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