Changes in calcineurin message, enzyme activity and protein content in the spinal dorsal horn are associated with chronic constriction injury of the rat sciatic nerve

Abstract

Plasticity in the spinal dorsal horn is thought to underlie the development of neuropathic pain. Calcineurin (protein phosphatase 3) plays an important role in plasticity in the brain. Here we examined whether chronic constriction injury (CCI) of the sciatic nerve modifies calcineurin expression in the spinal dorsal horn. Male rats were assigned to control (uninjured), sham-operated or CCI groups. CCI animals exhibited both a shift in weight bearing and a reduction in paw withdrawal latencies as signs of pain behavior. At 3 days (3D) the pain behavior was associated with a significant increase in calcineurin gene expression, enzyme activity and content of its Aα isoform in the ipsilateral spinal dorsal horn. In contrast, while the pain behavior persisted at 7 days (7D) calcineurin gene expression returned to control levels and activity and protein content decreased. A single intrathecal injection of MK-801 15 min before the ligation attenuated both signs of pain behavior in 3D but not 7D CCI animals. The same pre-treatment also prevented the CCI-associated increases in calcineurin in these animals. These data suggested an involvement of calcineurin in CCI-elicited neuropathic pain. The time-dependent divergent changes in calcineurin expression may underlie the different phases of neuropathic pain development.