title: Use of pharmaceutical and transgenic interventions in  dissection of neuropathic pain mechanisms in spinal cord injury
creator: Tolou Dabbaghian, Bahardokht
subject: ddc-500
subject: 500 Natural sciences and mathematics
subject: ddc-570
subject: 570 Life sciences
description: After experimental spinal cord injury (SCI), the emergence of neuropathic pain below the injury site is linked to heightened structural plasticity of nociceptive  fibers into deeper laminae of the dorsal horn. I have examined the role of prophylactic pregabalin (PGB), a commonly prescribed drug for SCI patients following neuropathic pain development, on this aberrant plasticity and the development of neuropathic pain. Prophylactic PGB administration (46 mg/kg, i.p., 2x/day, for 7 days) effectively averted mechanical allodynia and the plasticity  of peptidergic nociceptors into laminae III-IV in the lumbar spinal cord of male and female C57BL/6J mice subjected to a T11 moderate contusion. These beneficial effects against mechanical allodynia and the plasticity of nociceptive  fibers persisted for up to two weeks post-PGB discontinuation. To learn more about the specific role of nociceptors and their voltage-gated calcium channel  (VGCC) α2-δ2 subunit (Cacna2d2) −a selective PGB target− in the development of the neuropathic pain and aberrant plasticity I employed SNSCacna2d2 mice with a partial knockout of the α2-δ2 subunit specifically in nociceptors. Remarkably, these mice did not manifest thermal hyperalgesia nor mechanical allodynia postSCI, as confirmed by Hargreaves, von Frey hair filaments, and the place  escape/avoidance paradigm. Importantly, non-noxious mechanical hindpaw stimulation induced dorsal horn activation (c-fos) with significantly lower activation in both the PGB-treated and partial knockout mice. Laminae III-V of the dorsal horn exhibited the highest neuronal activation, aligning with the observed plasticity. Utilizing 3D imaging of nociceptor-labeled transgenic mice (SNStdTomato), this study reveals a post-SCI increase in volume of nociceptors in lower laminae of the dorsal horn, specifically starting from lamina III. This expansion suggests ventral sprouting rather than lateral. This thesis work underscores the pivotal role of nociceptors in neuropathic pain development following SCI, indicating their plasticity into deeper laminae establishes new connections transmitting mechanical allodynia potentially through wide dynamic neurons.
date: 2024
type: Dissertation
type: info:eu-repo/semantics/doctoralThesis
type: NonPeerReviewed
format: application/pdf
identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/34805/1/Thesis-Bahar%20Tolou.pdf
identifier: DOI:10.11588/heidok.00034805
identifier: urn:nbn:de:bsz:16-heidok-348052
identifier:   Tolou Dabbaghian, Bahardokht  (2024) Use of pharmaceutical and transgenic interventions in dissection of neuropathic pain mechanisms in spinal cord injury.  [Dissertation]     
relation: https://archiv.ub.uni-heidelberg.de/volltextserver/34805/
rights: info:eu-repo/semantics/openAccess
rights: http://archiv.ub.uni-heidelberg.de/volltextserver/help/license_urhg.html
language: eng