A Genome-wide Drosophila Screen for Heat Nociception Identifies alpha2delta3 as an Evolutionarily Conserved Pain Gene
Biomarkers of Pain
Worldwide, acute, and chronic pain affects 20% of the adult population and represents an enormous financial and emotional burden. Using genome-wide neuronal-specific RNAi knockdown in Drosophila, we report a global screen for an innate behavior and identify hundreds of genes implicated in heat nociception, including the alpha2delta family calcium channel subunit straightjacket (stj). Mice mutant for the stj ortholog CACNA2D3 (alpha2delta3) also exhibit impaired behavioral heat pain sensitivity. In addition, in humans, alpha2delta3 SNP variants associate with reduced sensitivity to acute noxious heat and chronic back pain. Functional imaging in alpha2delta3 mutant mice revealed impaired transmission of thermal pain-evoked signals from the thalamus to higher-order pain centers. Intriguingly, in alpha2delta3 mutant mice, thermal pain and tactile stimulation triggered strong cross-activation, or synesthesia, of brain regions involved in vision, olfaction, and hearing.
2010
Neely GG; Hess A; Costigan M; Keene AC; Goulas S; Langeslag M; Griffin RS; Belfer I; Dai F; Smith SB; Diatchenko L; Gupta V; Xia CP; Amann S; Kreitz S; Heindl-Erdmann C; Wolz S; Ly CV; Arora S; Sarangi R; Dan D; Novatchkova M; Rosenzweig M; Gibson DG; Truong D; Schramek D; Zoranovic T; Cronin SJ; Angjeli B; Brune K; Dietzl G; Maixner W; Meixner A; Thomas W; Pospisilik JA; Alenius M; Kress M; Subramaniam S; Garrity PA; Bellen HJ; Woolf CJ; Penninger JM
Cell
2010
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1016/j.cell.2010.09.047" target="_blank" rel="noreferrer">10.1016/j.cell.2010.09.047</a>
Leigh's syndrome
Female; Humans; Disease Progression; Autopsy; Severity of Illness Index; Risk Assessment; Biopsy; Magnetic Resonance Imaging; Fatal Outcome; infant; Q3 Literature Search; Needle; Basal Ganglia/pathology; Immunohistochemistry; Leigh Disease/diagnosis/physiopathology/therapy
A 15-month-old female child presented with sudden onset cough and hyperventilation along with evidence of metabolic acidosis. She had past history of recurrent vomiting, episodes of abnormal posturing, difficulty in deglutition and regression of milestones since 12 months of age. CT scan of the brain revealed hypodense lesions in bilateral basal ganglia and on MRI there were T2 hyperintensities in bilateral lentiform nuclei, caudate nuclei, thalamus, red nuclei and dentate nuclei. Biochemical examination revealed persistently elevated serum lactate levels with high lactate/pyruvate ratio. Resuscitative measures were of no avail and the child succumbed to the illness on the second day of admission. Neuropathological examination at autopsy demonstrated marked spongiosis, focal necrosis, endothelial proliferation, reactive astrogliosis and extensive demyelination involving bilateral basal ganglia, midbrain and spinal cord which were typical of Leigh's sub acute necrotizing encephalomyelopathy.
2004
Mannan AA; Sharma MC; Shrivastava P; Ralte AM; Gupta V; Behari M; Sarkar C
Indian Journal Of Pediatrics
2004
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1007/bf02828121" target="_blank" rel="noreferrer">10.1007/bf02828121</a>