Atwood, Brady K.El Jordi, OmarMcKinzie, David L.Oblak, Adrian L.Block, Michelle L.Sheets, Patrick L.2023-04-072023-04-072023-03https://hdl.handle.net/1805/32283http://dx.doi.org/10.7912/C2/3124Indiana University-Purdue University Indianapolis (IUPUI)Inflammation, specifically brain inflammation, can be both neuroprotective as well as detrimental in multiple neuropathic diseases. We investigated the inflammatory profile in two different receptor systems, opioids, and estrogens. Microglia, brain immune cells, can influence the neuron’s microenvironment and regulate neuronal activity via multiple signaling mediators. We investigated the role of microglia in opioid withdrawal in an oxycodone dependence paradigm. We found that microglial reduction had no effect on opioid withdrawal symptoms, glial activation markers, body temperature dysregulation, or select inflammatory cytokines. Interestingly, we found them involved in the acquisition of analgesic tolerance potentially mediated by the chemokine KC/GRO. This suggests that microglia modulate neuron adaptations to repetitive opioid dosing through chemokines or alternatively through direct interaction (cell-to-cell), indirect interaction through cytokines, or neurotransmitters that were not measured. In a different experiment, we investigated the effect of Raloxifene, a selective estrogen receptor modulator, in a model of lower back pain/spinal damage precipitated by intervertebral disc degeneration. Raloxifene’s therapeutic effect at the molecular level, verified by collaborators and evident by regeneration of healthy intervertebral disc tissue and reduction of pain signaling molecules (Substance P), did not translate to behavior. Our behavioral measures evaluating motor and psychological deficit, and ataxia were not altered by treatment. Interestingly, we found that hedonic behavior improved by the end of the treatment suggesting that Raloxifene may have a therapeutic effect on adverse sensory signals such as back pain resulting in reward-seeking behavior.en-USDissertation