Gordon-Williams, R.M.;
(2009)
Neuronal and non‐neuronal mechanisms in a rat model of cancer‐
induced bone pain.
Doctoral thesis , UCL (University College London).
Abstract
Development of animal models has furthered our understanding of mechanisms underpinning cancer-induced bone pain (CIBP). Cancer-induced bone pain is a unique pain state with mechanisms akin to those of chronic inflammatory and neuropathic pain. I aim to highlight the role of both neuronal and non-neuronal mechanisms in a rat model of cancer-induced bone pain (MRMT-1). Anti-convulsant drugs are useful in the treatment of neuropathic pain and have been shown to be effective in animal models of inflammatory pain. Carbamazepine reduced neuronal excitability seen at time of peak behaviour after MRMT-1 but not sham injection, highlighting the possible role of sodium channel activity in maintaining the neuronal excitability in cancer-induced bone pain. Furthermore carbamazepine reduced pain-like ipsilateral hypersensitivity after MRMT-1 injection in awake animals further indicating the usefulness of sodium channel antagonism in cancer-induced bone pain. Peptidergic C fibre population, which co-express calcitonin-gene related peptide (CGRP) and the receptor for nerve growth factor trkA, carry sensory information from bone. It is for these reasons that modulation of CGRP signalling in the MRMT-1 model of cancer-induced bone pain has been investigated using "drug X" (donated from Pfizer UK) which interrupts CGRP signalling in nociceptive pathways. Subcutaneous administration of drug X reduced ipsilateral pain-like behaviours seen following MRMT-1 injection, suggesting that CGRP antagonism may be a useful target in the treatment of cancer-induced bone pain. Microglia have been implicated in the pathophysiology underlying neuropathic pain and have become activated in models of cancer-induced bone pain. OX42 labelled microglial in the lumbar dorsal horn ipsilateral to MRMT-1 increase between days 5 and 11 post surgery. Microglial inhibition using minocycline between days 0 and 9 but not between days 5 and 9 post-MRMT-1 injection delays pain-like behaviour in the post-operative period, indicating that early microgliosis is key in the initiation of cancer-induced bone pain.
Type: | Thesis (Doctoral) |
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Title: | Neuronal and non‐neuronal mechanisms in a rat model of cancer‐ induced bone pain |
Language: | English |
UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology |
URI: | https://discovery.ucl.ac.uk/id/eprint/16651 |
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