Enhanced nociceptive behavior and expansion of associated primary afferents in a rabbit model of cerebral palsy
Spastic cerebral palsy (CP) is a movement disorder marked by hypertonia and hyperreflexia; 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...
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| Published in: | Journal of neuroscience research Vol. 100; no. 10; pp. 1951 - 1966 |
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| Main Authors: | , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Hoboken
Wiley Subscription Services, Inc
01-10-2022
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| Subjects: | |
| Online Access: | Get full text |
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| Summary: | Spastic cerebral palsy (CP) is a movement disorder marked by hypertonia and hyperreflexia; 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 min at ~70%–80% gestation). We found that HI caused an expansion of peptidergic afferents (marked by expression of calcitonin gene‐related peptide) in both the superficial and deep dorsal horn at postnatal day (P)5. Non‐peptidergic nociceptive afferent arborization (labeled by isolectin B4) 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 was unchanged within spinal cord white matter regions important in nociceptive transmission at P5. We found that mechanical and thermal nociception was enhanced 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.
Most individuals with cerebral palsy (CP) experience pain, yet it is understudied. We demonstrate altered distribution of nociceptive afferents in the dorsal horn of neonatal rabbits that experienced hypoxic–ischemic injury in utero; these anatomical changes were associated with nocifensive behavior indicative of pain. Our findings suggest that CP‐causative injuries alter spinal sensory pathways (not only descending motor circuits), contributing to increased pain in CP. |
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| Bibliography: | Edited by Cristina Antonella Ghiani and Dena R. Howland. Reviewed by Jeffrey Petruska. Correction added on July 21, 2022 after first online publication. The affiliations of Alyssa M. Garrett and Megan R. Detloff has been corrected in this version. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 EJ Reedich contributed to data curation, formal analysis, investigation, methodology, supervision, validation and writing, editing and reviewing the manuscript. LT Genry contributed to data curation, formal analysis, investigation, methodology, supervision, validation, and reviewing and editing the manuscript. MA Singer contributed to data curation, formal analysis, investigation, methodology, and validation. CF Cavarsan contributed to formal analysis, investigation, methodology, and validation. E Mena Avila contributed to data curation, formal analysis, investigation, methodology, validation, and reviewing the manuscript. DM Boudreau contributed to data curation, formal analysis, investigation, methodology, validation, and reviewing the manuscript. MC Brennan contributed to data curation, formal analysis, investigation, methodology, validation, and reviewing the manuscript. AM Garrett contributed to data curation, formal analysis, investigation, methodology, validation, and reviewing the manuscript. L Dowaliby contributed to investigation, methodology and supervision of this project. MR Detloff contributed to contributed to conceptualization, data curation, funding acquisition, project administration, resources, supervision, and writing, editing and review of the manuscript. KA Quinlan contributed to conceptualization, data curation, funding acquisition, project administration, resources, supervision, and writing, editing and review of the manuscript. Author contributions |
| ISSN: | 0360-4012 1097-4547 |
| DOI: | 10.1002/jnr.25108 |