Target engagement and histopathology of neuraxial resiniferatoxin in dog.
Vet Anaesth Analg
; 45(2): 212-226, 2018 Mar.
Article
en En
| MEDLINE
| ID: mdl-29361418
ABSTRACT
OBJECTIVE:
To evaluate target engagement of intracisternally (IC) delivered TRPV1 agonist, resiniferatoxin (RTX), as measured by primary afferent and dorsal horn substance P immunoreactivity (sP-IR), histopathology and thermal escape latencies in dogs. STUDYDESIGN:
Prospective experimental trial. ANIMALS Fourteen adult male Beagle dogs, weighing 10.3-13.2 kg; 11 dogs surviving to scheduled euthanasia.METHODS:
Anesthetized dogs were randomly assigned to be administered IC RTX (3.6 µg, 0.1 mL kg-1) in a hyperbaric (hRTX, n = 6), normobaric (nRTX, n = 4) vehicle or a hyperbaric vehicle (hVehicle, n = 4). Over 16 days, animals were examined for thoracic and pelvic limb paw thermal withdrawal latencies and neurologic function. Spinal cords, trigeminal ganglia and dorsal root ganglia (DRGs) were assessed for morphologic changes and sP-IR.RESULTS:
IC RTX in anesthetized dogs resulted in a < 1 hour increase in blood pressure. Acute reactions leading to euthanasia within 8 hours occurred in three dogs (two hRTX, one nRTX). All other animals recovered with normal neurologic, bowel and bladder function. Final groups were vehicle n = 4, hRTX n = 4 and nRTX n = 3. Animals in nRTX and hRTX showed increases in escape latencies in thoracic paws and, to a lesser extent, in pelvic paws, correlating to a loss of sP-IR in cervical cord with smaller reductions in thoracic and lumbar cord. In animals surviving to euthanasia, thickening of the arachnoid membrane (predominantly in the cervical region) was the most consistent change. This change, present in controls, was interpreted to be vehicle related. There was no evidence of structural changes in brain and spinal cord. CONCLUSIONS AND CLINICAL RELEVANCE IC RTX produced localized loss of spinal and DRG sP with a corresponding thermal analgesia, absent motor impairment or spinal pathology. Loss of three animals emphasizes the need to refine the use of this promising therapeutic modality in managing companion animal pain.Palabras clave
Texto completo:
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Base de datos:
MEDLINE
Asunto principal:
Diterpenos
/
Perros
/
Sistema Nervioso
/
Neurotoxinas
Límite:
Animals
Idioma:
En
Revista:
Vet Anaesth Analg
Asunto de la revista:
ANESTESIOLOGIA
/
MEDICINA VETERINARIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos