Loss of neurons from laminas I-III of the spinal dorsal horn is not required for development of tactile allodynia in the spared nerve injury model of neuropathic pain.
It has been proposed that death of inhibitory interneurons in the dorsal horn contributes to the neuropathic pain that follows partial nerve injury. In this study, we have used two approaches to test whether there is neuronal death in the dorsal horn in the spared nerve injury (SNI) model. We performed a stereological analysis of the packing density of neurons in laminas I-III 4 weeks after operation and found no reduction on the ipsilateral side compared with that seen on the contralateral side or in sham-operated or naive rats. In addition, we used two markers of apoptosis, terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) staining and immunocytochemical detection of cleaved (activated) caspase-3. Neither of these methods demonstrated apoptotic neurons in the dorsal spinal cord 1 week after operation. Although TUNEL-positive cells were present throughout the gray and white matter at this stage, they were virtually all labeled with antibody against ionized calcium-binding adapter molecule 1, a marker for microglia. All animals that underwent SNI showed clear signs of tactile allodynia affecting the ipsilateral hindpaw. These results suggest that a significant loss of neurons from the dorsal horn is not necessary for the development of tactile allodynia in the SNI model.
Polgár
Erika
E
Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, United Kingdom.
Hughes
David I
DI
Arham
Ahmad Z
AZ
Todd
Andrew J
AJ
D000344:Afferent Pathways / Q000503:physiopathology; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D002452:Cell Count; D006614:Hindlimb / Q000294:innervation; D006930:Hyperalgesia / Q000503:physiopathology*; D020287:In Situ Nick-End Labeling; D008297:Male; D017628:Microglia / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000032:analysis; D010543:Peroneal Nerve / Q000293:injuries*; D020427:Peroneal Neuropathies / Q000503:physiopathology*; D020671:Posterior Horn Cells / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012183:Retrograde Degeneration; D016037:Single-Blind Method; D013116:Spinal Cord / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D013979:Tibial Nerve / Q000293:injuries*; D020429:Tibial Neuropathy / Q000503:physiopathology*; D014110:Touch
D009419:Nerve Tissue Proteins; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases