title: Increased expression of acid-sensing ion channel 3 within dorsal root ganglia in a rat model of bone cancer pain.
abstract: In an attempt to investigate the underlying mechanisms of cancer-induced bone pain, we investigated the presence of acid-sensing ion channel 3 (ASIC3) in dorsal root ganglia (DRG) neurons in an animal model of bone cancer pain. Forty-five female Sprague-Dawley rats were randomized into three groups: sham-operation group (sham), cancer-bearing animals killed after 7 days (C7), and cancer-bearing animals killed after 14 days (C14). After establishment of the bone cancer pain model, pain-related behavioral tests were performed to determine the paw withdrawal threshold of mechanical allodynia and thermal hyperalgesia, respectively. Reverse transcription-PCR, western blot, and immunofluorescence were used to determine mRNA and protein expression of ASIC3 in ipsilateral and contralateral lumbar 4-5 DRG neurons. Compared with the sham group, paw withdrawal threshold of mechanical allodynia and thermal hyperalgesia in the C14 group showed a significant decrease (P<0.01) from postoperation day 7 to the termination of the experiment. Compared with the sham group, the ipsilateral but not contralateral mRNA of ASIC3 was upregulated in the C14 group. Meanwhile, the ipsilateral protein expression of ASIC3 was increased in the C7 and C14 group compared with the sham group. Double-labeled immunofluorescence showed that ASIC3 and isolectin-B4 (IB4)-colocalized small DRG neurons in the C14 group were more than that in the sham group. Furthermore, we also found that there were more ASIC3 and neurofilament 200 (NF200)-colocalized DRG neurons in the C14 group than in the sham group. The upregulation of mRNA and protein levels of ASIC3 suggested its potential involvement in the development and maintenance of cancer-induced bone pain.
authors.affiliation: aAnesthesia and Operation Center, Chinese PLA General Hospital bInstitute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Qiu
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wei
authors.forename: Shuzhuo
authors.initials: S
authors.lastname: Zhang
authors.forename: Weixiu
authors.initials: W
authors.lastname: Yuan
authors.forename: Weidong
authors.initials: W
authors.lastname: Mi
mesh_terms: D062565:Acid Sensing Ion Channels / Q000378:metabolism*; D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D007839:Functional Laterality; D005727:Ganglia, Spinal / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism; D006358:Hot Temperature; D006930:Hyperalgesia / Q000378:metabolism; D037102:Lectins / Q000378:metabolism; D008159:Lumbar Vertebrae; D009368:Neoplasm Transplantation; D009474:Neurons / Q000378:metabolism; D010146:Pain / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014110:Touch; D053675:Versicans
chemical_list: C568269:ASIC3 protein, rat; D062565:Acid Sensing Ion Channels; D006023:Glycoproteins; D037102:Lectins; D012333:RNA, Messenger; C508324:Vcan protein, rat; D053675:Versicans