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 taught

BMSC1213 - Basic Laboratory and Scientific Skills 2
BMSC2229 - Exp Skills: Medical Sciences
BMSC2232 - Topics in Physiology
BMSC3233/34/35/36/37 - ATUs - BMS specific
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 Tommaso Iannitti  (Research Fellow)

Dr Christopher Kay  (Postgraduate (BBSRC CASE funded))


Postgraduates

Natalie Griffiths  

Chapman RJ; Lall VK; Maxeiner S; Willecke K; Deuchars J; King AE Localization of neurones expressing the gap junction protein Connexin45 within the adult spinal dorsal horn: a study using Cx45-eGFP reporter mice. Brain Struct Funct 218 751-765, 2013
DOI:10.1007/s00429-012-0426-1
View abstract

Visockis V; King AE M-channels modulate network excitatory activity induced by 4-aminopyridine in immature rat substantia gelatinosa in vitro. Brain Res 1513 9-16, 2013
DOI:10.1016/j.brainres.2013.03.045
View abstract

Allen CE; Worsley MA; King AE; Boissonade FM Fos expression induced by activation of NMDA and neurokinin-1 receptors in the trigeminal subnucleus caudalis in vitro: Role of protein kinases BRAIN RES 1368 19-27, 2011
DOI:10.1016/j.brainres.2010.10.072

Nowak A; Mathieson HR; Chapman RJ; Janzso G; Yanagawa Y; Obata K; Szabo G; King AE Kv3.1b and Kv3.3 channel subunit expression in murine spinal dorsal horn GABAergic interneurones J CHEM NEUROANAT 42 30-38, 2011
DOI:10.1016/j.jchemneu.2011.02.003

Nowak A; Mathieson HR; Chapman RJ; King AE; Janzsó G; Yanagawa Y; Obata K; Szabo G Kv3.1b and Kv3.3 channel subunit expression in murine spinal dorsal horn GABAergic interneurones Journal of Chemical Neuroanatomy 42 30-38, 2011
DOI:10.1016/j.jchemneu.2011.02.003
View abstract

Chapman RJ; La Corte PFC; Asghar AUR; King AE Network-based activity induced by 4-aminopyridine in rat dorsal horn in vitro is mediated by both chemical and electrical synapses J PHYSIOL-LONDON 587 2499-2510, 2009
DOI:10.1113/jphysiol.2009.171777

Giles PA; Trezise DJ; King AE Differential activation of protein kinases in the dorsal horn in vitro of normal and inflamed rats by group I metabotropic glutamate receptor subtypes NEUROPHARMACOLOGY 53 58-70, 2007
DOI:10.1016/j.neuropharm.2007.04.003

Hilton KJ; Bateson AN; King AE Neurotrophin-induced preprotachykinin-A gene promoter modulation in organotypic rat spinal cord culture J NEUROCHEM 98 690-699, 2006
DOI:10.1111/j.1471-4159.2006.03910.x

King AE; Ackley MA; Cass CE; Young JD; Baldwin SA Nucleoside transporters: from scavengers to novel therapeutic targets TRENDS PHARMACOL SCI 27 416-425, 2006
DOI:10.1016/j.tips.2006.06.004

King AE The spinal cord in vitro: What can it tell us about nociception? Neurophysiology 38 410-420, 2006
DOI:10.1007/s11062-006-0079-x
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Asghar AU; Cilia La Corte PF; LeBeau FE; Al Dawoud M; Reilly SC; Buhl EH; Whittington MA; King AE Oscillatory activity within rat substantia gelatinosa in vitro: a role for chemical and electrical neurotransmission. J Physiol 562 183-198, 2005
DOI:10.1113/jphysiol.2004.076398
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Worsley MA; Todd AJ; King AE Serotoninergic-mediated inhibition of substance P sensitive deep dorsal horn neurons: a combined electrophysiological and morphological study in vitro Experimental Brain Research 160 360-367, 2005
DOI:10.1007/s00221-004-2018-7
View abstract

Governo RJM; Deuchars J; Baldwin SA; King AE Localization of the NBMPR-sensitive equilibrative nucleoside transporter, ENT1, in the rat dorsal root ganglion and lumbar spinal cord BRAIN RES 1059 129-138, 2005
DOI:10.1016/j.brainres.2005.08.017

Ackley MA; Baldwin SA; King AE Adenosine contributes to mu-opioid synaptic inhibition in rat substantia gelatinosa in vitro NEUROSCI LETT 376 102-106, 2005
DOI:10.1016/j.neulet.2004.11.034

Hilton KJ; Bateson AN; King AE A model of organotypic rat spinal slice culture and biolistic transfection to elucidate factors that drive the preprotachykinin-A promoter Brain Research Reviews 46 191-203, 2004
DOI:10.1016/j.brainresrev.2004.07.016
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Baldwin SA; Beal PR; Yao SYM; King AE; Cass CE; Young JD The equilibrative nucleoside transporter family, SLC29. Pflugers Archiv: European Journal of Physiology 447 735-743, 2004
DOI:10.1007/s00424-003-1103-2

Ackley MA; Governo RJ; Cass CE; Young JD; Baldwin SA; King AE Control of glutamatergic neurotransmission in the rat spinal dorsal horn by the nucleoside transporter ENT1 Journal of Physiology 548 507-517, 2003
DOI:10.1113/jphysiol.2002.038091
View abstract

Hilton KJ; Ackley MA; Bateson AN; King AE The use of organotypic slice cultures for the biolistic transfection of cells in the dorsal horn, 2002

Asghar AUR; Al Dawoud M; LeBeau FEN; Buhl EH; King AE The role of GABA(A) and glycine receptor-mediated inhibition on theta frequency oscillations in substantia gelatinosa neurones of the rat spinal cord in vitro, 2002

Asghar AUR; LeBeau FEN; Buhl EH; King AE Potassium-induced theta oscillations in rat substantia gelatinosa neurones of the spinal cord in vitro J PHYSIOL-LONDON 539 152P-153P, 2002

Asghar AUR; Bird GC; King AE Glutamate uptake inhibition modulates dorsal horn neurotransmission: a comparison between normal and arthritic rats NEUROREPORT 12 4061-4064, 2001

Bird G; Asghar AU; Ackley MA; King AE Modulation of primary afferent-mediated neurotransmission and Fos expression by glutamate uptake inhibition in rat spinal neurones in vitro Neuropharmacology 41 581-591, 2001
DOI:10.1016/S0028-3908(01)00111-3
View abstract

Badie-Mahdavi H; Worsley MA; Ackley MA; Asghar AUR; Slack JR; King AE A role for protein kinase intracellular messengers in substance P- and nociceptor afferent-mediated excitation and expression of the transcription factor Fos in rat dorsal horn neurons in vitro EUR J NEUROSCI 14 426-434, 2001

Bird GC; Asghar AUR; Ackley MA; King AE Modulation of primary afferent-mediated neurotransmission and Fos expression by glutamate uptake inhibition in rat spinal neurones in vitro NEUROPHARMACOLOGY 41 582-591, 2001

Ackley MA; Asghar AU; Worsley M; King AE Peripheral inflammation reduces the response of spinal dorsal horn neurons to an NK3 receptor agonist Neuroscience Letters 308 13-16, 2001
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Asghar AU; Hasan SS; King AE Actions of the anticonvulsant remacemide metabolic AR-R12495AA on afferent-evoked spinal synaptic transmission in vitro and on models of acute and chronic inflammation in the rat. Journal of Pharmacology and Experimental Therapeutics 294 876-883, 2000

Asghar AUR; Bird GC; King AE Glutamate transporters and modulation of primary afferent-mediated synaptic transmission in spinal dorsal horn neurones from normal and arthritic rats in vitro BRIT J PHARMACOL 131 U7-U7, 2000

Worsley MA; Badie-Mahdavi H; King AE Protein kinase a involvement in neurokinin- and nociceptive afferent- induced slow depolarisations and fos expression in rat spinal cord dorsal horn in vitro BRIT J PHARMACOL 131 U8-U8, 2000

Asghar AU; Hasan SS; King AE The anticonvulsant remacemide and its metabolite AR-R12495AA attenuate spinal synaptic transmission and carrageenan-induced inflammation in the young rat. European Journal of Pain 4 97-106, 2000

Khasabov SG; Lopez-Garcia JA; Asghar AU; King AE Modulation of afferent-evoked neurotransmission by 5-HT3 receptors in young rat dorsal horn neurones in vitro: a putative mechanism of 5-HT3 induced anti-nociception British Journal of Pharmacology 127 843-852, 1999

Khasabov SG; Lopez-Garcia JA; King AE; Asghar AU The role of 5-HT3 receptors in dorsal horn neurotransmission: mechanisms of endogenous analgesia. British Journal of Pharmacology 127 843-852, 1999

Chiter A; Blair GE; King AE The production of a transgenic rat expressing nerve growth factor using cell-type specific keratin promoters. Biochem Soc Trans 26 S144-, 1998

Khasabov SG; Lopez-Garcia JA; King AE Serotonin-induced population primary afferent depolarisation in vitro: the effects of neonatal capsaicin treatment. Brain Res 789 339-342, 1998
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King AE; Slack JR; Lopez-Garcia JA; Ackley MA Tachykinin actions on deep dorsal horn neurons in vitro: an electrophysiological and morphological study in the immature rat. European Journal of Neuroscience 9 1037-1046, 1997

Chiter A; King AE; Blair GE The role of neurotrophins in pathological pain states: a novel transgenic rat model of hyperalgesia. Biochem Soc Trans 25 209S-, 1997

Norris SK; King AE The stereo-isomers of the anticonvulsant ARL 12495AA limit sustained repetitive firing and modify action potential properties of rat hippocampal neurons in vitro. J Pharmacol Exp Ther 281 1191-1198, 1997
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Norris SK; King AE Electrophysiological effects of the anticonvulsant remacemide hydrochloride and its metabolite ARL 12495AA on rat CA1 hippocampal neurons in vitro. Neuropharmacology 36 951-959, 1997
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King AE; Ackley MA; Slack JR Profile of neuronal excitation following selective activation of the neurokinin-1 receptor in rat deep dorsal horn in vitro. Brain Res 767 55-63, 1997
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BadieMahdavi H; Withington DJ; McCrossan D; King AE Induction of c-fos in the auditory pathway following pure-tone or broadband noise stimulation., 1997

King AE; Liu XH Dual action metabotropic glutamate receptor agonists on neuronal excitability and synaptic transmission in spinal ventral horn neurons in vitro Neuropharmacology 35 1673-1680, 1996

Lopez-Garcia JA; King AE Pre- and post-synaptic actions of 5-HT in the rat lumbar dorsal horn in vitro: implications for somatosensory transmission. European Journal of Neuroscience 8 2188-2197, 1996

Lopez-Garcia JA; King AE A novel methodology for simultaneous assessment of the effects of 5-hydroxytryptamine on primary afferent polarisation and synaptic transmission in rat dorsal horn neurones in vitro. J Neurosci Methods 68 1-6, 1996
View abstract

KING AE; THOMPSON SWN BRIEF AND PROLONGED CHANGES IN SPINAL-INJURY EXCITABILITY FOLLOWING PERIPHERAL INJURY SEMIN NEUROSCI 7 233-243, 1995

Lopez-Garcia JA; King AE Membrane properties of physiologically classified rat dorsal horn neurons in vitro: correlation with cutaneous sensory afferent input. Eur J Neurosci 6 998-1007, 1994
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King AE; Lopez-Garcia JA Intracellular analysis of cutaneous afferent-induced excitation and inhibition in rat dorsal horn neurones in vitro. J Neurosci Methods 52 61-68, 1994
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King AE; Lopez-Garcia JA Excitatory amino acid receptor-mediated neurotransmission from cutaneous afferents in rat dorsal horn in vitro. J Physiol 472 443-457, 1993
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King AE; Lopez-Garcia JA; Cumberbatch M Antagonism of synaptic potentials in ventral horn neurones by 6-cyano-7-nitroquinoxaline-2,3-dione: a study in the rat spinal cord in vitro. Br J Pharmacol 107 375-381, 1992
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Thompson SW; King AE; Woolf CJ Activity-Dependent Changes in Rat Ventral Horn Neurons in vitro; Summation of Prolonged Afferent Evoked Postsynaptic Depolarizations Produce a d-2-Amino-5-Phosphonovaleric Acid Sensitive Windup. Eur J Neurosci 2 638-649, 1990
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King AE; Thompson SW; Woolf CJ Characterization of the cutaneous input to the ventral horn in vitro using the isolated spinal cord-hind limb preparation. J Neurosci Methods 35 39-46, 1990
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Woolf CJ; King AE Dynamic alterations in the cutaneous mechanoreceptive fields of dorsal horn neurons in the rat spinal cord. J Neurosci 10 2717-2726, 1990
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King AE; Thompson SW Characterization of deep dorsal horn neurones in the rat spinal cord in vitro: synaptic and excitatory amino acid induced excitations. Comp Biochem Physiol A Comp Physiol 93 171-175, 1989
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Woolf CJ; King AE Subthreshold components of the cutaneous mechanoreceptive fields of dorsal horn neurons in the rat lumbar spinal cord. J Neurophysiol 62 907-916, 1989
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King AE; Thompson SW; Urban L; Woolf CJ An intracellular analysis of amino acid induced excitations of deep dorsal horn neurones in the rat spinal cord slice. Neurosci Lett 89 286-292, 1988
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King AE; Thompson SW; Urban L; Woolf CJ The responses recorded in vitro of deep dorsal horn neurons to direct and orthodromic stimulation in the young rat spinal cord. Neuroscience 27 231-242, 1988
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Woolf CJ; Thompson SW; King AE Prolonged primary afferent induced alterations in dorsal horn neurones, an intracellular analysis in vivo and in vitro. J Physiol (Paris) 83 255-266, 1988
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Woolf CJ; King AE Physiology and morphology of multireceptive neurons with C-afferent fiber inputs in the deep dorsal horn of the rat lumbar spinal cord. J Neurophysiol 58 460-479, 1987
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KING AE; THOMPSON SWN; URBAN L; WOOLF CJ RESPONSE PROPERTIES OF NEURONS RECORDED FROM THE DEEP DORSAL HORN OF 14-16 DAY OLD RATS INVITRO J PHYSIOL-LONDON 390 P39-P39, 1987

FITZGERALD M; KING AE; THOMPSON SWN; WOOLF CJ THE POSTNATAL-DEVELOPMENT OF THE VENTRAL ROOT REFLEX IN THE RAT - A COMPARATIVE INVIVO AND INVITRO STUDY NEUROSCI LETT 78 41-45, 1987

KING AE; CHERUBINI E; NISTRI A A STUDY OF AMINO ACID-ACTIVATED CURRENTS RECORDED FROM FROG MOTONEURONS INVITRO NEUROSCI LETT 76 179-184, 1987

CORRADETTI R; KING AE; NISTRI A; ROVIRA C; SIVILOTTI L PHARMACOLOGICAL CHARACTERIZATION OF D-AMINOPHOSPHONOVALERIC ACID ANTAGONISM OF AMINO-ACID AND SYNAPTICALLY EVOKED EXCITATIONS ON FROG MOTONEURONES INVITRO - AN INTRACELLULAR STUDY BRIT J PHARMACOL 86 19-25, 1985

KING AE; NISTRI A; ROVIRA C THE EXCITATION OF FROG MOTONEURONES INVITRO BY THE GLUTAMATE ANALOG, DL-ALPHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLE-PROPIONIC ACID (AMPA), AND THE EFFECT OF AMINO-ACID ANTAGONISTS NEUROSCI LETT 55 77-82, 1985

ARENSON MS; BERTI C; KING AE; NISTRI A THE EFFECT OF D-ALPHA-AMINOADIPATE ON EXCITATORY AMINO-ACID RESPONSES RECORDED INTRACELLULARLY FROM MOTONEURONES OF THE FROG SPINAL-CORD NEUROSCI LETT 49 99-104, 1984