Michael Costigan, PhD

Department	Neurology, Affiliate - Program in Neurobiology
Hospital Title	Research Associate
Academic Title	Assistant Professor
Phone	617-919-2310
Fax	617-919-2772
Email	Michael Costigan
Location	300 Longwood Avenue CLS 12255 Boston MA 02115

Research Overview

I am principally interested in the reaction of the peripheral nervous system, and second order neurons of the spinal dorsal horn to axonal damage, whether these changes result in maladaptive phenotypes (chronic pain) (Costigan et al., 2009a)or adaptive ones (regeneration) (Richardson et al., 2009).  My focus is developing and using truly unbiased genetic research tools to obtain an unprecedented view of these mechanisms. From these data we wish to glean key genes and functional cascades, in order that these mechanisms can be proven in the laboratory, always with a view to translate such knowledge into future therapies.

To do this I use whole genome expression microarrays in rodents with Dr Griffin (MGH), Dr’s Moss & Fitzgerald (London, UK), and Dr’s Coppola & Geschwind (UCLA).  I use genome wide SNP arrays in humans, in collaboration with Dr’s Belfer & Lariviere (Pittsburgh), as well as Dr Diatchenko (UNC). I work with Dr’s Neely & Penninger (Vienna, Austria) to search drosophila genetics for relevant phenotypes (Neely et al., 2010). All of these data are combined to produce strong leads which are analyzed by multiple molecular methods prior to target development in humans.

Examples of such work include,

1.The identification and subsequent characterization of GTP Cyclohydrolase 1 (GCH1) as a determinant of pain sensitivity in rodents (Tegeder et al., 2006). Current work develops cutting edge transgenic animals to further investigate the tetrahydrobiopterin pathway in sensory neurons as well as defining other human pain targets (Costigan et al., 2010).

2.The identification and characterization of the role of the innate (Griffin et al., 2007)and the adaptive immune system (Costigan et al., 2009b)in neuropathic pain. Current work develops an understanding of how T-lymphocytes and myeloid cells interact to create neuropathic pain.

3.I am actively exploring the mechanisms of regeneration within peripheral nervous system (Mills et al., 2007)and am currently working up multiple exciting new genetic leads in this area.

Key Publications

• Costigan M, Scholz J, Woolf CJ (2009a) Neuropathic pain: a maladaptive response of the nervous system to damage. Annu Rev Neurosci 32:1-32.
• Costigan M, Moss A, Latremoliere A, Johnston C, Verma-Gandhu M, Herbert TA, Barrett L, Brenner GJ, Vardeh D, Woolf CJ, Fitzgerald M (2009b) T-cell infiltration and signaling in the adult dorsal spinal cord is a major contributor to neuropathic pain-like hypersensitivity. J Neurosci 29:14415-14422.
• Costigan M et al. (2010) Multiple chronic pain states are associated with a common amino acid-changing allele in KCNS1. Brain 133:2519-2527.
• Griffin RS, Costigan M, Brenner GJ, Ma CH, Scholz J, Moss A, Allchorne AJ, Stahl GL, Woolf CJ (2007) Complement induction in spinal cord microglia results in anaphylatoxin C5a-mediated pain hypersensitivity. J Neurosci 27:8699-8708.
• Mills CD, Allchorne AJ, Griffin RS, Woolf CJ, Costigan M (2007) GDNF selectively promotes regeneration of injury-primed sensory neurons in the lesioned spinal cord. Mol Cell Neurosci 36:185-194.
• Neely GG et al. (2010) A genome-wide Drosophila screen for heat nociception identifies alpha2delta3 as an evolutionarily conserved pain gene. Cell 143:628-638.
• Richardson PM, Miao T, Wu D, Zhang Y, Yeh J, Bo X (2009) Responses of the nerve cell body to axotomy. Neurosurgery 65:A74-79.
• Tegeder I et al. (2006) GTP cyclohydrolase and tetrahydrobiopterin regulate pain sensitivity and persistence. Nat Med 12:1269-1277.