Michelle Hook, PhD

Education and Training

• University of New England, PhD, 1998

Research Interests

• Effects of opioids on the prognosis for recovery after SCI. Morphine is one of the most frequently prescribed analgesics for the treatment of pain immediately after a spinal cord injury (SCI). We have shown, however, that irrespective of the route of administration morphine administered in the acute phase of a spinal cord injury significantly undermines recovery of locomotor function, decreases general health and produces symptoms of paradoxical pain in a rat model. The adverse effects of morphine on locomotor recovery may be mediated, at least in part, by increased neuronal death with drug administration. We have also shown that morphine is not the only opioid to produce adverse effects after SCI. Oxycodone and fentanyl, that are often used in pain management, also undermine recovery. We have begun to elucidate the molecular mechanisms underlying these adverse effects. Our data suggest that kappa-opioid receptors mediate the morphine-induced attenuation of recovery, and that glial cells may be involved in opioids adverse effect. We are extending these studies to test the effects of blocking the kappa opioid receptor when administering fentanyl and oxycodone. Oure goal is to identify an adjuvant that can be administered with opioids to provide safe and effective pain management after a spinal cord injury.
• Identifying the molecular mechanisms contributing to depression and cognitive impairment after spinal cord injury (SCI). The incidence of depression is significantly increased in spinally injured patients, relative to the general population. My lab has shown that depression-like behaviors are also increased in rats with SCI. We developed and validated a method for characterizing depression-like behavior in SCI rats, and have shown in preliminary studies that depression-like behavior is associated with non-subjective measures of physiological function (increased heart-rate, decreased heart-rate variability, decreased hippocampal neurogenesis) as well as elevated pro-inflammatory cytokine levels and decreased serotonin in the cortex. Importantly, as seen in humans, not all rats develop depression-like behavior following injury. Approximately one-third of the rats display depression behaviors, while two-thirds do not. Interestingly, the rats that develop depression-like behavior also show impairments on tests of spatial learning. We are now exploring the role of the gut in the development of depression-like behavior, as well as focusing on strategies that increase neurogenesis in the hippocampus, as a potential strategy for reversing cognitive deficits and depression. These innovative studies lay the foundation for a new area of research in neurotrauma models, and address a consequence of spinal injury that significantly impacts quality of life and likely impacts successful rehabilitation after injury. Understanding the molecular mechanisms underlying decreased psychological well-being will be important not only for SCI, but for a range of inflammatory based conditions including traumatic brain injury, stroke and multiple sclerosis.
• Factors contributing to bone loss after SCI. After spinal cord injury, 80% of individuals are diagnosed with osteopenia or osteoporosis. The dramatic loss of bone after SCI increases the potential for fractures 100-fold, with post-fracture complications occurring in 54% of cases. Numerous factors have been implicated in SCI-induced bone loss, but to date no effective therapies have been developed to either decrease the acute loss of bone or to facilitate bone formation in chronic phases of injury. My lab has started to investigate the SCI-induced changes that might contribute to the dramatic loss of bone after injury. Specifically we are focused on changes in the bone marrow niche induced by uncontrolled and increased sympathetic innervation below the level of injury. We hypothesize that increased sympathetic drive leads to changes in the activity of osteoblasts and osteoclasts, bone forming and resorbing cells respectively, as well and hematopoietic stem and precursor cells, that drive increased bone loss after injury.