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Pain, anxiety and motor behavior in early the postnatal time period after prenatal hypoxia-ischemia in New Zealand white rabbits
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Pain, anxiety and motor behavior in early the postnatal time period after prenatal hypoxia-ischemia in New Zealand white rabbits

Landon T. Genry, Corinne W. Marble, Brendan C. Moline, Patrick J. McGinnis, Cassandra Kramer, Scott Matson, Emily J. Reedich, Elvia Mena Avila, Tracy Santos, Lisa Dowaliby, …
2026
url
https://doi.org/10.7910/dvn/4myrsfView
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Abstract

allodynia hyperalgesia Medicine, Health and Life Sciences neonate neuropathic pain rabbit repeated measures Neuroscience
STUDY PURPOSE: The objective of this study was to characterize behavioral and neuroanatomical pain phenotypes in neonatal rabbits after prenatal hypoxia-ischemia or sham surgery. We assessed responses to multiple sensory modalities including mechanical, hot, and cold sensation. In addition to sensory discriminative aspects of pain, we also examined pain related anxiety. DATA COLLECTED: we performed an hypoxia-ischemia (HI) surgery to occlude blood flow to fetal New Zealand White rabbits for 40 minutes, or a sham surgery at ~75% gestation, and rabbit kits were born naturally, about 1 week later. von Frey, Hargreaves, and a cold allodynia test at postnatal (P)1, P5, P11, and P18. Data were also collected in the open field and two-texture preference test at P18 only for both sham and HI kits. The nociceptive primary afferent fiber density and distribution were assessed in the dorsal horn of the cervical level 7-8 and lumbar level4-5 spinal cord as the proportional area of calcitonin gene-regulated peptide positive and/or Isolectin-B4 positive tissue. Principal component analysis was conducted on behavioral and anatomical data. CONCLUSIONS: Data suggest that HI rabbits consistently display increased mechanical sensitivity and heat-evoked thermal sensitivity along with changes to the developmental trajectory of both sensory modalities. Consistent with these findings, at P18, HI kits display altered texture preferences compared to control kits and an increase in anxiety-like behavior. These behavioral changes are accompanied by an expansion of IB4+, nonpeptidergic primary afferent fibers in the lumbar dorsal horn and a trend towards a similar increase in the cervical dorsal horn in HI kits which may explain the increase in mechanical nociception in HI kits. Importantly, the prenatal rabbit hypoxia-ischemia generates pain behaviors similar to those seen in human cerebral palsy, suggesting that it may be a good model of cerebral palsy-associated pain.

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