The superoxide scavenger tempol attenuates DNA oxidative injury and spontaneous pain-like behavior in chronic post-cast pain model rats

• Published in: Biochemical and biophysical research communications 2020-12, Vol.533 (4), p.745-750
• Main Authors: Ohmichi, Yusuke, Ohmichi, Mika, Naito, Munekazu
• Format: Article
• Language: English
• Subjects: 8-Hydroxy-2'-Deoxyguanosine - metabolism; Animals; Antioxidants - administration & dosage; Chronic Pain - drug therapy; Chronic Pain - metabolism; Chronic post-cast pain; Complex regional pain syndrome type I; Cyclic N-Oxides - administration & dosage; DNA - drug effects; Gastrocnemius muscle; Hindlimb - drug effects; Hindlimb - metabolism; Male; Muscle Fibers, Fast-Twitch - metabolism; Muscle, Skeletal - metabolism; Oxidative stress; Oxidative Stress - drug effects; Rats; Rats, Sprague-Dawley; Soleus muscle; Spin Labels; Superoxides
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2020.09.044

The mechanism of severe pain occurring because of physical disuse, such as complex regional pain syndrome Type I, has not been elucidated so far. Therefore, to investigate this mechanism, we have developed a model called a chronic post-cast pain (CPCP) model. Oxidative stress-related factors generated in a fixed limb may be triggers for nociceptive signals due to physical disuse. On the basis of the results of our previous studies, we speculated that oxidative stress-related factors in immobilized hind limbs may also be triggers of nociceptive signals due to physical disuse. In this study, we aimed to clarify whether an oxidative stress-related factor is involved in the induction of nociceptive signals. The time course of oxidative damage in the soleus (slow-twitch fiber) and gastrocnemius (fast-twitch fiber) muscles was evaluated by immunostaining of 8-hydroxy-2′-deoxyguanosine (a marker of oxidative damage in DNA). We also investigated the effects of tempol, a scavenger of superoxide, on oxidative damage in DNA, spontaneous pain-related behaviors (licking and/or biting and flinching), and the activation of spinal dorsal horn neurons (c-Fos). Systemic administration of tempol before cast removal attenuated oxidative damage to DNA in immobilized skeletal muscles, suppressed spontaneous pain-related behavior, and suppressed the activation of spinal dorsal horn neurons. We suggest that superoxide generated in immobilized skeletal muscles after cast removal is one of the peripheral factors that trigger nociceptive signals. •8-OHdG immunoreactivity increases in skeletal muscles after physical disuse.•8-OHdG immunoreactivity is attenuated by tempol, a superoxide scavenger.•Tempol suppresses the 8-OHdG immunoreactivity after physical disuse.•Tempol also suppresses spontaneous pain-like behaviors and spinal neural activity.•We suggest that superoxide immobilized muscles trigger nociceptive signals.