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Title: Mechanisms of neurokinin₁ receptor action in the dorsal horn of the spinal cord
Author: Heppenstall, Paul Alexander
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1998
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This study addressed the role of neurokin1 (NK1) receptors in nociceptive transmission and their participation in a series of events involving glycine and NMDA receptor-mediated effects on spinal neurons. Using an in vivo electrophysiology protocol utilising ionosphoresis and extracellular recording from laminae III-V dorsal horn neurones of anaesthetised rats, the mechanisms of these interactions were assessed. The functions of the inflammatory cytokine leukaemia inhibitory factor (LIF) were also considered. Injury-induced alterations in the spinal expression pattern of this factor and the consequences of these changes to neuropeptide and excitatory amino acid expression were measured using in situ hybridisation. 1. The involvement of NK1 receptors in spinal pain transmission may be dependent upon the duration and intensity of the nociceptive stimulus. 2. NK1 receptors can contribute to the processing of sustained nociceptive stimuli by modulating excitatory amino acid-mediated transmission, particularly through potentiation of NMDA receptor activity. 3. LIF is a neuroactive cytokine that is associated with peripheral nerve injury. Using in situ hybridisation, the present study has examined the distribution of LIF mRNA in the spinal cord, normally or following peripheral inflammation or nerve injury and determined the consequences of intrathecally applied LIF on spinal expression of NK1 receptor and the high affinity glutamate transporter, EAAT2. In control animals, dorsal horn expression of LIF was high in superficial laminae I-II with only light expression in the deeper laminae III-V and in the ventral horn. Both peripheral inflammation and neuropathy significantly increased levels of LIF mRNA in the dorsal horn and this was most evident in the lateral parts of laminae I and II. Interactions within the spinal cord may underlie the plasticity of the dorsal horn in sensory processing. This has been discussed with reference to the regulation of short-term co-operation between NK1 and NMDA receptors by glycine and to long-term modifications of peptide and excitatory amino acid neurotransmission by altered LIF gene expression.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available