Pain Sensitivity and Inflammatory Gene Expression in Young and Aged Rat Spinal Cord in Response to Surgery and Morphine
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Publisher:The Ohio State University
Series/Report no.:The Ohio State University. Department of Biomedical Engineering Honors Theses; 2020
After surgery, older adults are particularly vulnerable to experiencing increased and poorly controlled pain (Halaszynski, 2013). Despite its common use after surgery, there is evidence that chronic morphine treatment contributes to increased pain sensitivity, or hyperalgesia (Joly et al., 2005). In young adult animals, morphine has been shown to incite an inflammatory response, evidenced by the upregulation of pro-inflammatory molecules, such as TLR4, NLRP3, NFkB, IL1B, and TNFa, in the spinal cord (Grace et al., 2016; Grace et al., 2019). Here, we examine the effect of age and morphine treatment on post-operative hyperalgesia and begin to examine a possible underlying mechanism. Aged (24 mo) and young adult (3 mo) male F344xBN F1 rats underwent either a laparotomy (exploratory abdominal surgery) or a sham surgery. After, they were either treated with saline or 2 mg/kg/ml morphine twice a day for 7 days. A Von Frey test for pain sensitivity was conducted at 2 and 8 weeks post-surgery. qPCR was run to measure mRNA gene expression of proinflammatory mediators IL1, IL6, HMGB1, TNFa, and NLRP3 in dorsal horn samples taken at L4/L5 vertebrae. In a second experiment, aged rats were treated with the inflammatory cytokine IL1 receptor antagonist (IL-1RA) immediately prior to surgery and morphine treatment; 2 weeks later rats completed a Von Frey test. At two weeks post-surgery, aged rats who underwent laparotomy and morphine treatment exhibited significantly lower pain thresholds than sham controls, saline-treated controls, or young controls. IL-1RA pre-treatment significantly improved pain sensitivity compared to saline-pretreated rats. However, pain threshold was still significantly lower than rats that had never received morphine in the first place. Preliminary gene expression data suggest a main effect of age elevating inflammatory markers, although no interaction effects with morphine were evident. The ameliorating effects of IL-1RA pre-treatment suggests that IL-1β may play a role in the observed surgery+morphine-induced enhanced pain in aged rats. Investigating post-operative inflammation in other spinal cord segments and examining genes expression of pain mediation downstream of acute inflammation may help elucidate the mechanisms underlying morphine-induced hyperalgesia in aged rats. More generally, a better understanding of how the aging body reacts to morphine and to an external insult needs to be reached in order to mitigate unnecessary pain through appropriate pre- and post-operative care.
Academic Major: Biomedical Engineering
National Institute on Aging RF1AG028271
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