Chronic fatigue syndrome is a disabling disorder indicated by unintended chronic fatigue, exertion intolerance, and sleep and cognitive abnormalities. Patients with CFS normally complain of long-lasting fatigue and pain which often does not go by resting, rather worsens by physical exertion. Earlier evidences have implicated that metaboreceptors of muscles play an essential role in chronic fatigue and the pain. Therefore, it was hypothesized that blocking impulse input from the deep tissues with intramuscular lidocaine injections would increase not only the pain but also fatigue in CFS patients.

A double-blind, placebo-controlled study was performed which included 58 CFS patients. The participants were given 20 mL of 1% lidocaine (200 mg) or normal saline once into both trapezius and gluteal muscles. The study aimed to determine the association between clinical fatigue and pain, depression, and anxiety. Mechanical and heat hyperalgesia was also assessed. Serum levels of lidocaine were obtained after administering the injections.

The findings of the study estimated the more significant decrease in Fatigue ratings among CFS patients after lidocaine comparative to saline injections (p=0.03). On the other hand, it was found that muscle injections lowered the pain, depression, and anxiety (p<0.001). However, these changes were not statistically varied between lidocaine and saline (p>0.05). It was observed that there was an increase in the mechanical pain thresholds among CFS patients (p=0.04) with use of lidocaine injections. But it did not affect their heat hyperalgesia. Importantly, mood changes or lidocaine serum levels did not significantly predict fatigue reductions.

Overall, it can be concluded that lidocaine injections bring about a reduction in clinical fatigue in CFS patients significantly more than placebo. This suggests an essential role of peripheral tissues in chronic fatigue. Moreover, a further investigation to evaluate the clinical benefits through these interventions are warranted.