Investigations into inflammation and nerve regeneration in a human model system of neuropathic pain

Thesis

Neuropathic pain is a serious and debilitating disease affecting a large proportion of the population. The disease is caused by direct damage to the nervous system and is often chronic in nature. Neuropathic pain is typically poorly treated, with patients often experiencing inadequate relief from symptoms. Part of this issue stems from ineffective treatment options while a lack of understanding of the disease pathology also presents as a major issue.

Recent findings have emerged which implicate the immune system in the initiation and generation of neuropathic pain. These studies have highlighted the role of inflammatory mediators including cytokines and immune cells as being heavily involved in the development of neuropathic pain. The majority of this work has been conducted in pre-clinical animal models where severe nerve injury paradigms are used. These experiments have proven useful in identifying the role of inflammation in neuropathic pain but do not necessarily reflect the nerve injury present in humans. Furthermore, preclinical findings do not always translate to patients in the clinic, which has resulted in a deficit in novel, effective neuropathic pain therapies. The mechanisms of nerve regeneration that occur after nerve injury are also incompletely understood. Similar to neuropathic pain, much work has been done using animal model systems of nerve regeneration, however human nerve regeneration presents with unique challenges and is often incomplete. Further studies are therefore required in humans to elucidate the precise role and action of inflammation in patients with neuropathic pain and to determine the mechanisms that are driving nerve regeneration after injury.

Carpal tunnel syndrome is an entrapment neuropathy commonly occurring in patients which presents as a unique model system with which to study neuropathic pain. Due to the unparalleled opportunity to collect tissues from these patients, both inflammation and nerve regeneration can be explored in the context of neuropathic pain. This thesis will firstly endeavour to describe and characterise inflammatory associations with neuropathic pain in patients with carpal tunnel syndrome using both genetic and molecular approaches. Using these same approaches, I will also investigate nerve regeneration after injury to uncover mediators stimulating nerve growth and determine associations with inflammation in this process.

Authors: Sandy-Hindmarch, O

• DOI: 10.5287/ora-azw5x7zky
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: Nerve Injury; Neuropathic Pain; Pain; Inflammation; Nerve Regeneration
• Subjects: Pain; Inflammation; Neurosciences