title: Exercise preconditioning reduces neonatal incision surgery-induced enhanced hyperalgesia via inhibition of P38 mitogen-activated protein kinase and IL-1β, TNF-α release.
abstract: Neonatal surgery leads to enhanced hyperalgesia to noxious stimulation in adulthood via a mechanism caused by enhanced phosphorylated (p)-p38 expression in microglia. We tested the effect of exercise on reducing enhanced hypersensitivity primed by neonatal incision surgery. Adult female Wistar rats, with or without neonatal incision surgery at postnatal day (P) 3, received right hind paw plantar incision surgery under anesthesia at P44. The rats performed wheel-running exercise from P22 to P41. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were measured and ipsilateral spinal cords were collected for protein quantification. For PWT and PWL, exercise reduced the pain index after incision surgery at P44 in rats with neonatal surgery (P<0.01). Western blots showed that exercise suppressed P-p38 expression relative to adult rats without neonatal surgery (P<0.05). Results of ELISA showed that exercise reduced IL-1β and TNF-α (P<0.05) concentration in the ipsilateral spinal cord. Exercise preconditioning is an effective approach to reducing enhanced adult hyperalgesia primed by neonatal surgery. The mechanism may be explained by exercise-induced inhibition of P-p38 activation and IL-1β, TNF-α release.
authors.affiliation: Department of Anesthesiology & Pediatric Clinical Pharmacology Laboratory, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xingrui
authors.initials: X
authors.lastname: Gong
authors.affiliation: Department of Anesthesiology & Pediatric Clinical Pharmacology Laboratory, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Anesthesiology & Pediatric Clinical Pharmacology Laboratory, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: zmzscmc@shsmu.edu.cn.
authors.forename: Mazhong
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007839:Functional Laterality; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006930:Hyperalgesia / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D020382:Interleukin-18 / Q000378:metabolism*; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology; D010149:Postoperative Pain / Q000150:complications; D010805:Physical Conditioning, Animal / Q000379:methods*; D010812:Physical Stimulation / Q000009:adverse effects; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D020382:Interleukin-18; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Exercise preconditioning; Hyperalgesia; Neonate; P38 mitogen-activated protein kinase