title: Role of TRPM8 in dorsal root ganglion in nerve injury-induced chronic pain.
abstract: BACKGROUND
  Chronic neuropathic pain is an intractable pain with few effective treatments. Moderate cold stimulation can relieve pain, and this may be a novel train of thought for exploring new methods of analgesia. Transient receptor potential melastatin 8 (TRPM8) ion channel has been proposed to be an important molecular sensor for cold. Here we investigate the role of TRPM8 in the mechanism of chronic neuropathic pain using a rat model of chronic constriction injury (CCI) to the sciatic nerve.
  
  
  RESULTS
  Mechanical allodynia, cold and thermal hyperalgesia of CCI rats began on the 4th day following surgery and maintained at the peak during the period from the 10th to 14th day after operation. The level of TRPM8 protein in L5 dorsal root ganglion (DRG) ipsilateral to nerve injury was significantly increased on the 4th day after CCI, and reached the peak on the 10th day, and remained elevated on the 14th day following CCI. This time course of the alteration of TRPM8 expression was consistent with that of CCI-induced hyperalgesic response of the operated hind paw. Besides, activation of cold receptor TRPM8 of CCI rats by intrathecal application of menthol resulted in the inhibition of mechanical allodynia and thermal hyperalgesia and the enhancement of cold hyperalgesia. In contrast, downregulation of TRPM8 protein in ipsilateral L5 DRG of CCI rats by intrathecal TRPM8 antisense oligonucleotide attenuated cold hyperalgesia, but it had no effect on CCI-induced mechanical allodynia and thermal hyperalgesia.
  
  
  CONCLUSIONS
  TRPM8 may play different roles in mechanical allodynia, cold and thermal hyperalgesia that develop after nerve injury, and it is a very promising research direction for the development of new therapies for chronic neuroapthic pain.
authors: Department of Anesthesiology, General Hospital of Tianjin Medical University, Anshan Road No. 154, Heping District, Tianjin, 300052, China.
authors: Lin
authors: L
authors: Su
authors: Chao
authors: C
authors: Wang
authors: Yong-Hao
authors: YH
authors: Yu
authors: Yong-Ying
authors: YY
authors: Ren
authors: Ke-Liang
authors: KL
authors: Xie
authors: Guo-Lin
authors: GL
authors: Wang
mesh_terms: D000818:Animals; D059350:Chronic Pain / Q000378:metabolism*; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism*; D006930:Hyperalgesia / Q000378:metabolism; D008297:Male; D009619:Nociceptors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000378:metabolism; D050053:TRPM Cation Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D013997:Time Factors
chemical_list: D050053:TRPM Cation Channels; C498947:Trpm8 protein, rat