title: Disruption of δ-opioid receptor phosphorylation at threonine 161 attenuates morphine tolerance in rats with CFA-induced inflammatory hypersensitivity.
abstract: OBJECTIVE
  Our previous study identified Threonine 161 (Thr-161), located in the second intracellular loop of the δ-opioid receptor (DOR), as the only consensus phosphorylation site for cyclin-dependent kinase 5 (Cdk5). The aim of this study was to assess the function of DOR phosphorylation by Cdk5 in complete Freund's adjuvant (CFA)-induced inflammatory pain and morphine tolerance.
  
  
  METHODS
  Dorsal root ganglion (DRG) neurons of rats with CFA-induced inflammatory pain were acutely dissociated and the biotinylation method was used to explore the membrane localization of phosphorylated DOR at Thr-161 (pThr-161-DOR), and paw withdrawal latency was measured after intrathecal delivery of drugs or Tat-peptide, using a radiant heat stimulator in rats with CFA-induced inflammatory pain.
  
  
  RESULTS
  Both the total amount and the surface localization of pThr-161-DOR were significantly enhanced in the ipsilateral DRG following CFA injection. Intrathecal delivery of the engineered Tat fusion-interefering peptide corresponding to the second intracellular loop of DOR (Tat-DOR-2L) increased inflammatory hypersensitivity, and inhibited DOR- but not µ-opioid receptor-mediated spinal analgesia in CFA-treated rats. However, intrathecal delivery of Tat-DOR-2L postponed morphine antinociceptive tolerance in rats with CFA-induced inflammatory pain.
  
  
  CONCLUSIONS
  Phosphorylation of DOR at Thr-161 by Cdk5 attenuates hypersensitivity and potentiates morphine tolerance in rats with CFA-induced inflammatory pain, while disruption of the phosphorylation of DOR at Thr-161 attenuates morphine tolerance.
authors.affiliation: Neuroscience Research Institute, Peking University, Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors.forename: Hai-Jing
authors.initials: HJ
authors.lastname: Chen
authors.forename: Wei-Yan
authors.initials: WY
authors.lastname: Xie
authors.forename: Fang
authors.initials: F
authors.lastname: Hu
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence / Q000187:drug effects / Q000502:physiology; D000701:Analgesics, Opioid / Q000009:adverse effects; D000818:Animals; D004195:Disease Models, Animal; D004361:Drug Tolerance / Q000502:physiology*; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D006967:Hypersensitivity / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology*; D007249:Inflammation / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D013912:Threonine / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D017465:Receptors, Opioid, delta; D013912:Threonine; D009020:Morphine