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| Everlasting Effects of Primary Life Pain on Osteoarthritis Pain in a Premature |
Saba Nawaz, Muhammad Jahanzaib Malik, Zubair Ahmed
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Abstract:
One in ten newborns are born premature, receiving an average of 14 painful procedures daily in the hospital. The developing nervous system readily alters in response to noxious stimuli due to a particular propensity for neuroplasticity and immature descending inhibitory mechanisms. Early-life, injury-induced alterations can lead to increased severity of subsequent painful events, but its effects on later osteoarthritis (OA) are unknown. Here, we investigate the impact of early repetitive needle prick (RNP) pain on subsequent adult OA pain. Neonatal Sprague-Dawley received a series of RNPs or tactile (TS) stimuli from postnatal day 1 to 7. At 17-weeks, OA (RNP-OA; TS-OA) and control (RNP-C; TS-C) groups were created. Stifle OA was induced via intra-articular monoiodoacetate injection. Limb use, reflexive, and behavioral assays were performed at intervals. During the 6-week period following OA-induction, RNP-OA had reduced ipsilateral limb use compared to others characterized by: decreased static weight-bearing, increased time to maximum paw- floor contact, and reduced print length during locomotion. RNP-OA showed less activity (p=0.047) and decreased time spent in the center of an open field (p=0.023). Histological scoring of stifles showed that OA caused more damage than controls (p<0.005), with the highest scores in female RNP-OA (p<0.030). Spinal microglia in RNP-OA were more activated later in life, as measured by intensity, quantity, and morphological features (p<0.049). We conclude that early RNP injury appears to heighten pain due to monoiodoacetate induced-OA, over OA alone, in adults, as defined by clinically relevant limb use, histology, and microglia activation, with similar trends in reflexive and complex behaviors.
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