TY - JOUR

T1 - Dorsal horn volume loss and pain pathway changes in Cavalier King Charles Spaniels with syringomyelia, signs of pain, and phantom scratching

AU - Mortensen, Danny

AU - Thoefner, Maria Soendergaard

AU - Agerholm, Joergen Steen

AU - Slumstrup, Lasse

AU - Jensen, Troels Staehelin

AU - Bjerrum, Ole Jannik

AU - Berendt, Mette

AU - Nyengaard, Jens Randel

N1 - Funding Information: Funding of the study was provided by PhD fellowship resources granted by the Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Center for Stochastic Geometry and Advanced Bioimaging is supported by Villum Foundation. Additional funding was received from Fondet for Sygdomsbekæmpelse hos vore Familiedyr and the Jens Anker Andersen Foundation. An abstract on the main results was accepted for poster presentation at the 7th International Congress on Neuropathic Pain in London, United Kingdom, in May 2019. The authors thank Prof Lisbeth Høier Olsen, Department of Veterinary and Animal Sciences, Section for Experimental Animal Models, University of Copenhagen, Denmark, for the dedicated collaboration and help during recruitment of CKCS controls for the study. The authors express their deepest gratitude to biomedical laboratory technologist Helene Marie Andersen and postdoc. Stine Hasselholt at the Core Center for Molecular Morphology, Section for Stereology and Microscopy, Aarhus University, Denmark for their dedicated technical help and invaluable academic input; to laboratory technician Heidi Elise Holm at the Department of Veterinary Clinical Sciences, University of Copenhagen for technical help; to Prof Gulgun Sengul, Ege University, School of Medicine, Izmir, Turkey, for invaluable inputs regarding the use of primary antibodies to delineate the dorsal horn's laminae I-III. The authors have no arrangements, financial or otherwise, which may serve as a conflict of interest. Research material transparency and data transparency. If any researcher is interested in the raw material and raw data, they are welcome to contact one of the corresponding authors, and arrangements will be made for data and material transfer.

PY - 2022

Y1 - 2022

N2 - Central neuropathic pain is a core clinical sign of syringomyelia in humans and Cavalier King Charles Spaniel (CKCS) dogs. This histopathological study used spinal cords from CKCS dogs with syringomyelia to investigate the following conditions: (1) whether specific structural cervical spinal cord entities involved in nociception were affected by loss of neuroparenchyma or other pathological changes in CKCS dogs with pain-related behaviour and phantom scratching, (2) whether pain-related behaviour or phantom scratching correlated with loss of a specific anatomical entity or upregulation of glia cells, and (3) whether syringomyelia-related lesions affected specific functional spinal cord units of nociception. Spinal cord segments C1-C8 from CKCS dogs with magnetic resonance imaging-confirmed syringomyelia and clinical signs of pain and phantom scratching (n = 8) were compared with those from CKCS dogs without syringomyelia (n = 4). Dogs with unilateral scratching (n = 7) had a volume loss (P = 0.043) of the dorsal horn laminae I-III in the ipsilateral side compared with the contralateral dorsal horn. A clear pattern of ipsilateral changes in the dorsal root entry zone characterised by deafferentation and reorganization of first-order axons into deeper laminae was found in cases with lateralised scratching. Significant changes in cell number density were not found for astrocytes or microglia, suggesting that the dogs represented cases of end-stage syringomyelia and thus could not reveal astrogliosis and microgliosis, which may be involved in the early phases of syrinx development and phantom scratching. The present relationship between clinical findings and dorsal horn and pain pathway pathology in CKCS dogs suggests that these dogs may be of interest as a supplement to experimental model pain research.

AB - Central neuropathic pain is a core clinical sign of syringomyelia in humans and Cavalier King Charles Spaniel (CKCS) dogs. This histopathological study used spinal cords from CKCS dogs with syringomyelia to investigate the following conditions: (1) whether specific structural cervical spinal cord entities involved in nociception were affected by loss of neuroparenchyma or other pathological changes in CKCS dogs with pain-related behaviour and phantom scratching, (2) whether pain-related behaviour or phantom scratching correlated with loss of a specific anatomical entity or upregulation of glia cells, and (3) whether syringomyelia-related lesions affected specific functional spinal cord units of nociception. Spinal cord segments C1-C8 from CKCS dogs with magnetic resonance imaging-confirmed syringomyelia and clinical signs of pain and phantom scratching (n = 8) were compared with those from CKCS dogs without syringomyelia (n = 4). Dogs with unilateral scratching (n = 7) had a volume loss (P = 0.043) of the dorsal horn laminae I-III in the ipsilateral side compared with the contralateral dorsal horn. A clear pattern of ipsilateral changes in the dorsal root entry zone characterised by deafferentation and reorganization of first-order axons into deeper laminae was found in cases with lateralised scratching. Significant changes in cell number density were not found for astrocytes or microglia, suggesting that the dogs represented cases of end-stage syringomyelia and thus could not reveal astrogliosis and microgliosis, which may be involved in the early phases of syrinx development and phantom scratching. The present relationship between clinical findings and dorsal horn and pain pathway pathology in CKCS dogs suggests that these dogs may be of interest as a supplement to experimental model pain research.

KW - Astrocytes

KW - Chiari malformation

KW - Dorsal root entry zone

KW - Microglia

KW - SMI-32

KW - Spinocervicothalamic tract

KW - Spinothalamic tract

KW - Stereology

U2 - 10.1097/j.pain.0000000000002630

DO - 10.1097/j.pain.0000000000002630

M3 - Journal article

C2 - 35353770

AN - SCOPUS:85142401317

VL - 163

SP - 2365

EP - 2379

JO - Pain

JF - Pain

SN - 0304-3959

IS - 12

ER -