title: Interleukin-1β overproduction is a common cause for neuropathic pain, memory deficit, and depression following peripheral nerve injury in rodents.
abstract: BACKGROUND
  Chronic pain is often accompanied by short-term memory deficit and depression. Currently, it is believed that short-term memory deficit and depression are consequences of chronic pain. Here, we test the hypothesis that the symptoms might be caused by overproduction of interleukin-1beta (IL-1β) in the injured nerve independent of neuropathic pain following spared nerve injury in rats and mice.
  
  
  RESULTS
  Mechanical allodynia, a behavioral sign of neuropathic pain, was not correlated with short-term memory deficit and depressive behavior in spared nerve injury rats. Spared nerve injury upregulated IL-1β in the injured sciatic nerve, plasma, and the regions in central nervous system closely associated with pain, memory and emotion, including spinal dorsal horn, hippocampus, prefrontal cortex, nucleus accumbens, and amygdala. Importantly, the spared nerve injury-induced memory deficits, depressive, and pain behaviors were substantially prevented by peri-sciatic administration of IL-1β neutralizing antibody in rats or deletion of IL-1 receptor type 1 in mice. Furthermore, the behavioral abnormalities induced by spared nerve injury were mimicked in naïve rats by repetitive intravenous injection of re combinant rat IL-1β (rrIL-1β) at a pathological concentration as determined from spared nerve injury rats. In addition, microglia were activated by both spared nerve injury and intravenous injection of rrIL-1β and the effect of spared nerve injury was substantially reversed by peri-sciatic administration of anti-IL-1β.
  
  
  CONCLUSIONS
  Neuropathic pain was not necessary for the development of cognitive and emotional disorders, while the overproduction of IL-1β in the injured sciatic nerve following peripheral nerve injury may be a common mechanism underlying the generation of neuropathic pain, memory deficit, and depression.
authors.affiliation: Department of Physiology and Pain Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China Guangdong Province Key Laboratory of Brain Function and Disease, Guangzhou, China.
authors.forename: Wen-Shan
authors.initials: WS
authors.lastname: Gui
authors.affiliation: Department of Physiology and Pain Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China Guangdong Province Key Laboratory of Brain Function and Disease, Guangzhou, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Physiology and Pain Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China Guangdong Province Key Laboratory of Brain Function and Disease, Guangzhou, China.
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Mai
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ, USA.
authors.forename: Madhuvika
authors.initials: M
authors.lastname: Murugan
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ, USA.
authors.forename: Long-Jun
authors.initials: LJ
authors.lastname: Wu
authors.affiliation: Department of Physiology and Pain Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China Guangdong Province Key Laboratory of Brain Function and Disease, Guangzhou, China.
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Xin
authors.affiliation: Department of Physiology and Pain Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China Guangdong Province Key Laboratory of Brain Function and Disease, Guangzhou, China Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ, USA.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Zhou
authors.affiliation: Department of Physiology and Pain Research Center, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China Guangdong Province Key Laboratory of Brain Function and Disease, Guangzhou, China liuxg@mail.sysu.edu.cn zhou.lijun@yahoo.com.
authors.forename: Xian-Guo
authors.initials: XG
authors.lastname: Liu
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D001522:Behavior, Animal; D003863:Depression / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D017353:Gene Deletion; D006930:Hyperalgesia / Q000378:metabolism / Q000473:pathology; D007275:Injections, Intravenous; D053583:Interleukin-1beta / Q000097:blood / Q000378:metabolism*; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009437:Neuralgia / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D059348:Peripheral Nerve Injuries / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000172:deficiency / Q000378:metabolism; D012584:Sciatic Nerve / Q000187:drug effects / Q000293:injuries* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D066148:Spinal Cord Dorsal Horn / Q000187:drug effects / Q000473:pathology; D013997:Time Factors
chemical_list: D057134:Antibodies, Neutralizing; D053583:Interleukin-1beta; D017472:Receptors, Interleukin-1
keywords: Neuropathic pain; depression; interleukin-1β; microglia; peripheral nerve injury; short-term memory deficit