title: Muscle fatigue increases the probability of developing hyperalgesia in mice.
abstract: Chronic muscle pain is a major clinical problem that is often associated with fatigue. Conversely, chronic fatigue conditions are commonly associated with muscle pain. We tested the hypothesis that muscle fatigue enhances hyperalgesia associated with injection of acidic saline into muscle. We evaluated mechanical sensitivity of the paw (von Frey) in mice after 2 intramuscular injections of saline (20 microL; pH 4, pH 5, pH 6, pH 7.2) in a fatigue and a control group. To induce fatigue, mice were run for 2 h/day for 2 days prior to the first injection and 2 h/day for 2 days prior to the second injection. Muscle lactate, pCO(2), pO(2), creatinine kinase, phosphate, and histology were examined after the fatigue task and compared to a control group. Grip force was significantly decreased after 2 h of running indicating fatigue. The fatigue task did not induce muscle damage as there was no difference in muscle lactate, pCO(2), pO(2), creatinine kinase, phosphate, or histology. The fatigue task altered the dose-response relationship to intramuscular acidic saline injections. Mechanical hyperalgesia was observed in both fatigue and control groups after intramuscular injection of pH 4.0, but only the fatigue group after injection of pH 5. Neither the fatigue nor the control group developed hyperalgesia in response to intramuscular injection of pH 6 or pH 7.2. In conclusion, fatigue modified the susceptibility of mice to acid injection of pH 5.0 to result in mechanical hyperalgesia after 2 injections of pH 5.0. The fatigue task did not produce measurable changes in the muscle tissue suggesting a central mechanism mediating the enhancement of hyperalgesia.
  
  
  CONCLUSIONS
  These data therefore show that muscle fatigue can enhance the likelihood that one develops pain to a mild insult. Clinically, this could relate to the development of pain from such conditions as repetitive strain injury, and may relate to the interrelationship between chronic pain and fatigue.
authors.affiliation: Physical Therapy and Rehabilitation Science Graduate Program, Department of Pathology, Pain Research Program, University of Iowa, Iowa City, Iowa 52242, USA.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Tammy L
authors.initials: TL
authors.lastname: Lisi
authors.forename: Steven A
authors.initials: SA
authors.lastname: Moore
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Sluka
mesh_terms: D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D012090:Cumulative Trauma Disorders / Q000150:complications / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015673:Fatigue Syndrome, Chronic / Q000150:complications / Q000503:physiopathology; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology*; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology; D007511:Ischemia / Q000378:metabolism / Q000503:physiopathology; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018763:Muscle Fatigue; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000378:metabolism / Q000503:physiopathology*; D010100:Oxygen / Q000378:metabolism; D010147:Pain Measurement; D010725:Phosphocreatine / Q000378:metabolism; D010812:Physical Stimulation; D012965:Sodium Chloride / Q000009:adverse effects
chemical_list: D010725:Phosphocreatine; D002245:Carbon Dioxide; D019344:Lactic Acid; D012965:Sodium Chloride; D010100:Oxygen