Enhanced nociceptor sprouting in a rabbit model of cerebral palsy

• Published in: bioRxiv
• Main Authors: Reedich, Emily J, Genry, Landon T, Singer, Meredith A, Clarissa Fantin Cavarsan, Elvia Mena Avila, Boudreau, Daphne M, Brennan, Michael C, Garrett, Alyssa M, Dowaliby, Lisa, Detloff, Megan R, Quinlan, Katharina A
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 17.12.2021
• Subjects: Calcitonin; Calcitonin gene-related peptide; Cerebral palsy; Dorsal horn; Gestation; Hypoxia; Injuries; Ischemia; Nociceptors; Pain; Pain perception; Paralysis; Peptides
• DOI: 10.1101/2021.09.28.462176

Spastic cerebral palsy (CP) is a movement disorder marked by hypertonia and hyperreflexia, and the most prevalent comorbidity is pain. Since spinal nociceptive afferents contribute to both the sensation of painful stimuli as well as reflex circuits involved in movement, we investigated the relationship between prenatal hypoxia-ischemia (HI) injury which can cause CP, and possible changes in spinal nociceptive circuitry. To do this, we examined nociceptive afferents and mechanical and thermal sensitivity of New Zealand White rabbit kits after prenatal HI or a sham surgical procedure. As described previously, a range of motor deficits similar to spastic CP was observed in kits born naturally after HI (40 minutes at ~70-80% gestation). We found that HI caused an expansion of peptidergic afferents (marked by expression of calcitonin gene-related peptide; CGRP) in both the superficial and deep dorsal horn at postnatal day (P)5. Non-peptidergic nociceptive afferent arborization (labeled by isolectin B4; IB4) was unaltered in HI kits but overlap of the two populations (peptidergic and non-peptidergic nociceptors) was increased by HI. Density of glial fibrillary acidic protein (GFAP) was unchanged within spinal white matter regions important in nociceptive transmission at P5. We found that mechanical and thermal allodynia was present in HI kits even in the absence of motor deficits. These findings suggest that prenatal HI injury impacts spinal sensory pathways in addition to the more well-established disruptions to descending motor circuits. In conclusion, changes to spinal nociceptive circuitry could disrupt spinal reflexes and contribute to pain experienced by individuals with CP. Competing Interest Statement The authors have declared no competing interest.