title: Thalidomide Promotes Morphine Efficacy and Prevents Morphine-Induced Tolerance in Rats with Diabetic Neuropathy.
abstract: Opioid analgesics have less efficacy in diabetic neuropathy treatment, and tolerance often occurs after chronic usage. Given that thalidomide can potentiate the morphine efficacy in diabetic neuropathy treatment, we investigated the effects of intrathecal administrations of thalidomide on morphine tolerance during the treatment of diabetic neuropathy. We found that intrathecal administrations of thalidomide (25 mg/kg/ml) potentiated the analgesic effects of morphine on mechanical hyperalgesia and prevented the development of morphine tolerance. While this treatment regimen did not alter the protein levels of μ-opioid receptor (MOR) in the spinal cord of diabetic rats, chronic morphine treatment robustly increased MOR binding density in the synaptic plasma membranes fraction, but decreased it in the microsomal fraction. Furthermore, thalidomide was able to reverse the distribution of MOR altered by chronic morphine treatment. Finally, STZ-induced diabetes promoted PKC activation and enhanced TNFα level in the spinal cord, which were attenuated by intrathecal administrations of thalidomide. Taken together, these results suggested that thalidomide may potentiate morphine efficacy on diabetic neuropathy and prevent the development of morphine tolerance by suppressing PKC activation and TNFα level in the spinal cord.
authors: Department of Anesthesiology, The First Hospital of Shijiazhuang, No. 36 Fanxi Road, Chang'an District, Shijiazhuang, 050011, Hebei, China.
authors: Jianhui
authors: J
authors: Zhao
authors: Department of Anesthesiology, The First Hospital of Shijiazhuang, No. 36 Fanxi Road, Chang'an District, Shijiazhuang, 050011, Hebei, China.
authors: Hong
authors: H
authors: Wang
authors: Department of Anesthesiology, The First Hospital of Shijiazhuang, No. 36 Fanxi Road, Chang'an District, Shijiazhuang, 050011, Hebei, China. tysong1234@163.com.
authors: Tieying
authors: T
authors: Song
authors: Department of Anesthesiology, The First Hospital of Shijiazhuang, No. 36 Fanxi Road, Chang'an District, Shijiazhuang, 050011, Hebei, China.
authors: Yunliang
authors: Y
authors: Yang
authors: Department of Anesthesiology, The First Hospital of Shijiazhuang, No. 36 Fanxi Road, Chang'an District, Shijiazhuang, 050011, Hebei, China.
authors: Kunfeng
authors: K
authors: Gu
authors: Department of Anesthesiology, The First Hospital of Shijiazhuang, No. 36 Fanxi Road, Chang'an District, Shijiazhuang, 050011, Hebei, China.
authors: Pengyu
authors: P
authors: Ma
authors: Department of Anesthesiology, Bethune International Peace Hospital, No. 398 Zhongshan Road, Shijiazhuang, 050000, Hebei, China.
authors: Zaiwang
authors: Z
authors: Zhang
authors: Department of Intensive Care Unit, Hebei General Hospital, No. 348 Heping west Road, Shijiazhuang, 050051, Hebei, China.
authors: Limin
authors: L
authors: Shen
authors: Department of Thoracic Surgery, The First Hospital of Shijiazhuang, No. 36 Fanxi Road, Chang'an District, Shijiazhuang, 050011, Hebei, China.
authors: Jiabao
authors: J
authors: Liu
authors: Department of Gynaecology, The Sixth Hospital of Shijiazhuang, No. 9 Jianguo Road, Shijiazhuang, 050081, Hebei, China.
authors: Wenli
authors: W
authors: Wang
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D004357:Drug Synergism; D004361:Drug Tolerance; D004789:Enzyme Activation; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology; D007262:Infusions, Intravenous; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000494:pharmacology* / Q000627:therapeutic use; D010812:Physical Stimulation; D011493:Protein Kinase C / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013311:Streptozocin; D013792:Thalidomide / Q000494:pharmacology* / Q000627:therapeutic use; D014110:Touch; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide; D013311:Streptozocin; D009020:Morphine; D011493:Protein Kinase C
keywords: Diabetic neuropathy; Spinal cord; Streptozocin; Thalidomide; μ-Opioid receptor