Chronic Muscle Pain Associated Depression-Like Behavior and Gene Regulation

• Main Authors: Chien-Ju Chen, 陳芊如
• Other Authors: 陳志成
• Format: Others
• Language: en_US
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/50287930448858158298

碩士 === 國立臺灣大學 === 動物學研究所 === 97 === Chronic wide-spread pain of skeletal muscle (CWP) has long been a major health problem around the world. 10-15% of the general population reports affected while approximately 90% of the patients are female. In addition to chronic, widespread musculoskeletal allodynia/hyperalgesia, sleep and emotion disorders are also commonly found in patients with CWP syndrome. To study CWP and related chronic muscle pain, Sluka et al. had developed an animal model where repeated injections of acidic saline into one gastrocnemius muscle produced a long-lasting bilateral hyperalgesia without tissue damage. Strikingly, the phenotype is abolished in mice lacking Acid sensing ion channel 3 (Asic3). However, whether this model has associated emotional disorder and the underlying neuronal mechanisms of pain transduction, especially the role of ASIC3, has not been tested. In the present study, we found female Asic3 wild type (Asic3+/+) but not knockout (Asic3-/-) mice showed increased depression-like behavior 7 days after induction of hyperalgesia while male mice appeared to be normal. Decease of locomoton activity was found in male Asic3-/- mice and Asic3+/+ mice receiving intramuscular acid injection. ERK activity was increased in spinal cord dorsal horn after the second acidic saline injection in both Asic3+/+ and Asic3-/- mice. Also, there was prolonged up-regulation of Cav3.2, mgluR1, mgulR5 transcripts in lumbar spinal cord after second acid injection in Asic3+/+ mice. In contrast, the mRNA level of spinal NR2A was increased in Asic3-/- mice. We further examined whether the chronic muscle hyperalgesia involved brain facilitation pathways that affect both pain transduction and emotional disorder. However, the results of immunohistochemistry revealed no significant change in ERK activity in brain regions related to descending pain pathway or depression behavior. In sum, the present study revealed that 1) ASIC3-mediated chronic muscle pain would selectively trigger depression-like behaviors in female mice; 2) ASIC3-dependent central sensitization is involved in the up-regulation of Cav3.2, mgluR1, mgluR5, and NR2A in spinal cord. More works need to be carried out to determine the involvement of super spinal region in the acid-induced hyperalgesia/depression. Key words: muscle, hyperalgesia, ASIC3, depression, pERK, spinal cord