Cellular sources of cyclooxygenase-1 and -2 up-regulation in the spinal dorsal horn after spinal nerve ligation

Aims: Recent studies suggested that the development of neuropathic pain associated with neural injury may be partly due to up-regulation of cyclooxygenase (COX) in the central nervous system. However, the cellular sources of COX-1 and COX-2 up-regulation following nerve injury are unclear. Methods: We investigated the spinal cellular sources of COX-1 and COX-2 in association with allodynia following L5 spinal nerve ligation (SNL). Results: Post-SNL pain-related behaviour was shown by increased sensitivity to mechanical stimulation. There was a significant increase in both COX-1 and COX-2 immunoreactivity (P<0.01) on the ipsilateral side of spinal dorsal horn. Double immunofluorescence labelling demonstrated that COX-1 immunoreactive cells colocalized chiefly with dorsal horn neuronal nuclei and microglia, whereas COX-2 was expressed in neuronal cytoplasm. Conclusion: These findings demonstrate that while spinal dorsal horn neurones are important source of COX-1 and COX-2 after nerve injury, microglia also contribute to the pathogenesis of neuropathic pain, partly by producing additional COX-1.