Inhibition of protein kinase C restores morphine efficacy following excitotoxic spinal cord injury: Implications for the treatment of post-spinal cord injury pain syndromes

The development of neuropathic pain following spinal cord injury occurs in up to 90% of patients within five years post-injury. The most common analgesic for the treatment of pain, morphine, exhibits significantly reduced efficacy in the treatment of neuropathic pain. The reduced efficacy of morphine in models of morphine tolerance has been related to changes in mu opioid receptor phosphorylation and protein kinase C levels. Therefore, the purpose of this work was to determine the relationship of changes in mu opioid receptor phosphorylation and protein kinase C levels to the development of overgrooming, which is believed to be a correlate of at-level neuropathic pain following excitotoxic spinal cord injury. The results demonstrate that decreased morphine efficacy following excitotoxic spinal cord injury can be related to increased phosphorylation of mu opioid receptor. Additionally, increased protein kinase C expression preceded increased mu opioid receptor phosphorylation. The administration of calphostin C, a PKC inhibitor, restored morphine efficacy in overgrooming animals following acute intracisternal injection and chronic intracisternal administration reduced the development of thermal hyperalgesia and maintained morphine efficacy.