Faculty of Biological Sciences

Prof Anne King

BSc, Aberdeen; PhD 1983, Southampton.
Chair of Translational Neuroscience
School of Biomedical Sciences

Contact:  Garstang G6.31f | +44(0) 113 34 34243 | email address for  

Research Interests

Spinal cord neurophysiology and neuropharmacology - molecular and cellular aspects of pain.

Dr. King’s and her group work on signaling and neuronal communication in the mammalian spinal cord.  The focus of this work is synaptic modulation of somatosensory processing in the sensory dorsal horn with a particular emphasis on synaptic transmission between peripheral sensory afferents and target spinal neurons that underpin nociception (pain).  From a clinical perspective, the effective treatment of chronic debilitating pain represents a huge scientific challenge.  There are many forms of persistent pain e.g. chronic back pain, cancer, neuropathic and inflammatory pain that affect large numbers of people and for which there is no effective long term pain management strategy.  Heroin-based drugs are not a universal panacea and cannot be used reliably for some forms of pain e.g. pediatric or neuropathic pain. Thus, an additional important aspect of this research, undertaken with our industrial collaborators, is to identify novel targets for development of new generation analgesics. Our work provides an understanding of the basic neurobiology and neuropharmacology of pain at the level of spinal cord and periphery, thereby building a platform for drug discovery and therapeutic advances for clinical pain management.  Techniques include electrophysiology (patch-clamp or sharp microelectrode, multi-site microelectrode arrays) on spinal cord in vitro (slices for IR imaging and targeted neuronal recording or hemisected preparations) combined with neuroanatomical immunofluorescence/confocal analysis, and/or  Molecular Biology (RT-PCR) and transgenic rodent models to study basic principals of network organization/ neuroplasticity.


Current projects

1) Rhythmicity in spinal dorsal horn sensory processing:- In contrast to other CNS areas, the phenomenon of rhythmicity in spinal dorsal horn is poorly understood.  We are characterizing synaptic (GABA-ergic) and non-synaptic (gap junction) mechanisms of synchronized dorsal horn ensemble activity in vitro and determining novel modulatory influences of analgesic drug families such as opioids and cannabinoids.  Studies underway include electrophysiological and anatomical analyses of transgenic mice with GFP-tagged PV +ve GABAergic interneurons and RT-PCR assessment of Connexin (putative gap junction) expression in dorsal horn.  Confocal/EM studies of fixed tissue and dye-filled single cells will be used to examine architecture of network circuitry. Funded by The Wellcome Trust (2005-2008).

2) The trigeminal system and oro-facial pain:- this is a joint project between Prof Boissonade (Sheffield) and Dr King that uses techniques in-vivo and in-vitro. The overall aim is to investigate use-dependent synaptic plasticity in trigeminal system as a consequence of prolonged neuronal activation such as occurs during chronic dental and facial pain. The project focuses on stimulation-transcription coupling and the signaling cascades that are activated following prolonged nociceptive afferent input, e.g. repetition of acute peripheral stimuli or peripheral nerve injury and inflammation. We are examining these mechanisms in the trigeminal nucleus using Fos, pERK, pCREB and p38 as molecular markers of neuronal activation and plasticity. Mechanistic comparisons between trigeminal and spinal systems suggest that whilst some parallels can be drawn between the two models, the trigeminal system displays some distinctive elements with regard to signaling cascades activated by chronic pain. Funded by BBSRC (2007-2009).

3) Gap junction connectivity and Connexin protein expression in sensory spinal cord: novel facilitators of neuropathic pain? This is an Industrial Partnership project between Dr. A.E. King (PI) and Drs. E. Sher (Head of Pain Research, Neuroscience R&D) and D. Ursu (Senior Researcher, Neuroscience R&D.) based at Eli Lilly, UK.  The project uses a multidisciplinary approach to characterize the expression and function of connexin (Cx) proteins, the molecular constituents of gap junctions (GJs), in transgenic rodent models, mammalian spinal cord dorsal horn of naïve rats and those with a neuropathic injury.  Recently, major progress has been made in terms of identifying the genes that encode for connexin (Cx) proteins and describing their distribution within the mammalian CNS but there is a paucity of related data for spinal dorsal horn.  Previous data from the applicant’s lab and other published data infer a role for GJs in cellular connectivity across dorsal horn nociceptive circuitry.  The broader hypothesis driving the project is that disruption of normal dorsal horn connectivity, putatively via altered Cx expression, may be linked to aberrant sensory processing and facilitation of pathological (neuropathic) pain.  A better understanding of the factors underlying pathological pain would pave the way to improved therapies for intractable neuropathic pain. (Funded by BBSRC 2008-2010)

Current Funding Sources
The Wellcome Trust and BBSRC

Current Lab Members
Dr Rebecca Chapman, Postdoctoral fellow (BBSRC funded)
Christopher Kay, Ph.D. student (BBSRC CASE funded).

Positions available – none currently

 

Faculty Research and Innovation



Studentship information

Undergraduate project topics:

  • Vacation studentships - Studentships funded by Physiological Society or The Wellcome trust (competitive applications) are available for 2nd Year undergraduates wishing to undertake some research during the summer vacation

Postgraduate studentship areas:

See also:

Admin roles

FBS Athena SWAN rep
FBS Equality and Diversity Committee
FBS Faculty Board
FBS UGTSEC
UG Programme Leader: Physiology

Modules managed

BMSC3145 - Advanced Topics in Physiology I
BMSC3235 - Advanced Topics in Physiology II

Modules taught

BMSC1103 - Basic Laboratory and Scientific Skills
BMSC1213 - Basic Laboratory and Scientific Skills 2
BMSC2229 - Exp Skills: Medical Sciences
BMSC2232 - Topics in Physiology
BMSC3145 - Advanced Topics in Physiology I
BMSC3233/34/35/36 - ATUs - BMS specific
BMSC3235 - Advanced Topics in Physiology II
BMSC3301 - Research Proj: Biomed Sciences

Committees

Member of Undergraduate School Taught Student Education Committee

Centre membership: Neuroscience Research at Leeds (NeuR@L)

Group Leader Prof Anne King  (Chair of Translational Neuroscience)

Spinal cord neurophysiology and neuropharmacology - molecular and cellular aspects of pain. 


Dr Christopher Kay  (Visiting Research Fellow)

Postgraduates

Natalie Griffiths  
Rae Larmour