BackgroundThe present study aimed to investigate whether head and neck cooling (at 18 °C next to the skin) and fatiguing submaximal exercise at a thermoneutral ambient temperature can induce peripheral and central responses in healthy men and those with multiple sclerosis (MS). MethodsA local head–neck cooling (at 18 °C next to the skin) intervention in men with a relapsing-remitting form of MS (n = 18; age 30.9 ± 8.1 years) and healthy men (n = 22; age 26.7 ± 5.9 years) was assessed. Men in both groups performed 100 intermittent isometric knee extensions with 5 s contractions and 20 s of rest. The primary variables were measured before exercise, after 50 and 100 repetitions, and 1 h after recovery. The central activation ratio, maximal voluntary contraction, electrically induced force, electromyography, contractile properties, blood markers, muscle temperature, and perception of effort were measured. ResultsCompared with noncooled conditions, head and neck cooling increased the central capacity to activate exercising muscles but resulted in greater exercise-induced peripheral fatigue in men with MS (p < 0.05). Local cooling did not affect motor accuracy or the amplitude of electromyography signals; however, these factors were related to the intensity of the motor task (p > 0.05). The changes in central and peripheral fatigability induced by local cooling during submaximal exercise were more pronounced in men with MS than in healthy men (p < 0.05). ConclusionHead and neck cooling enhances central activation of muscles during exercise, leading to improved exercise performance compared with noncooled conditions in men with MS.