Exogenously applied muscle metabolites synergistically evoke sensations of muscle fatigue and pain in human subjects

Pollak, Kelly A.; Swenson, Jeffrey D.; VanHaitsma, Timothy A.; Hughen, Ronald W.; Jo, Dae Hyun; Light, Kathleen C.; Schweinhardt, Petra; Amann, Markus; Light, Alan R.

doi:10.1113/expphysiol.2013.075812

Cited by 191 publications

(223 citation statements)

References 69 publications

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“…It should also be noted that lactate accumulation alone is unlikely to be the causal agent. When lactate was applied to the thumb muscle at concentrations that arise during ischemic exercise, it did not cause acute pain [517]. The pain and fatigue ratings rose only when lactate was combined with protons and ATP, possibly because several different types of metabosensitive receptors need to be activated before a pain signal is transmitted.…”

Section: Muscle Ischemiamentioning

confidence: 92%

Fibromyalgia: A Critical and Comprehensive Review

Borchers

Gershwin

2015

Clinic Rev Allerg Immunol

229

217

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Fibromyalgia is a disorder that is part of a spectrum of syndromes that lack precise classification. It is often considered as part of the global overview of functional somatic syndromes that are otherwise medically unexplained or part of a somatization disorder. Patients with fibromyalgia share symptoms with other functional somatic problems, including issues of myalgias, arthralgias, fatigue and sleep disturbances. Indeed, there is often diagnostic and classification overlap for the case definitions of a variety of somatization disorders. Fibromyalgia, however, is a critically important syndrome for physicians and scientists to be aware of. Patients should be taken very seriously and provided optimal care. Although inflammatory, infectious, and autoimmune disorders have all been ascribed to be etiological events in the development of fibromyalgia, there is very little data to support such a thesis. Many of these disorders are associated with depression and anxiety and may even be part of what has been sometimes called affected spectrum disorders. There is no evidence that physical trauma, i.e., automobile accidents, is associated with the development or exacerbation of fibromyalgia. Treatment should be placed on education, patient support, physical therapy, nutrition, and exercise, including the use of drugs that are approved for the treatment of fibromyalgia. Treatment should not include opiates and patients should not become poly pharmacies in which the treatment itself can lead to significant morbidities. Patients with fibromyalgia are living and not dying of this disorder and positive outlooks and family support are key elements in the management of patients.

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Section: Muscle Ischemiamentioning

confidence: 92%

Fibromyalgia: A Critical and Comprehensive Review

Borchers

Gershwin

2015

Clinic Rev Allerg Immunol

229

217

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“…In an intriguing recent study, Pollak et al (252) infused metabolites known to be produced during exercise into the abductor pollicis brevis muscle of the hand of healthy humans. Although the sensations of skeletal muscle fatigue and pain were the main outcome variables of this study, rather than cardiovascular or autonomic responses, this approach holds great promise to further probe the metabolite(s) responsible for stimulating skeletal muscle afferents and evoking the exercise pressor reflex mediated cardiovascular response.…”

Section: Skeletal Muscle Metaboreflex During Steady-state Exercisementioning

confidence: 98%

Autonomic Adjustments to Exercise in Humans

Fisher

Young

Fadel

2015

Comprehensive Physiology

231

253

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Autonomic nervous system adjustments to the heart and blood vessels are necessary for mediating the cardiovascular responses required to meet the metabolic demands of working skeletal muscle during exercise. These demands are met by precise exercise intensity-dependent alterations in sympathetic and parasympathetic nerve activity. The purpose of this review is to examine the contributions of the sympathetic and parasympathetic nervous systems in mediating specific cardiovascular and hemodynamic responses to exercise. These changes in autonomic outflow are regulated by several neural mechanisms working in concert, including central command (a feed forward mechanism originating from higher brain centers), the exercise pressor reflex (a feed-back mechanism originating from skeletal muscle), the arterial baroreflex (a negative feed-back mechanism originating from the carotid sinus and aortic arch), and cardiopulmonary baroreceptors (a feed-back mechanism from stretch receptors located in the heart and lungs). In addition, arterial chemoreceptors and phrenic afferents from respiratory muscles (i.e., respiratory metaboreflex) are also capable of modulating the autonomic responses to exercise. Our goal is to provide a detailed review of the parasympathetic and sympathetic changes that occur with exercise distinguishing between the onset of exercise and steady-state conditions, when appropriate. In addition, studies demonstrating the contributions of each of the aforementioned neural mechanisms to the autonomic changes and ensuing cardiac and/or vascular responses will be covered.

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“…Recently, two different subtypes of chemosensitive group III/IV muscle afferents characterized by anatomical and functional differences have been discovered in animals (17, 30, 34, 40, 45) and humans (50). One subtype, the so-called metabo- or ergoreceptors, was documented to only respond to innocuous levels of intramuscular metabolites (lactate, ATP, protons) associated with ‘normal’ (i.e.…”

Section: Subtypes Of Group Iii/iv Muscle Afferents: Critical Considermentioning

confidence: 99%

“…freely perfused and predominantly aerobic) exercise (14, 31, 39) up to strenuous intensities. In contrast, the other subtype, the so-called metabonociceptors, only respond to higher (and concurrently noxious) levels of metabolites present in muscle during ischaemic contractions or following hypertonic saline infusions – but not to non-noxious metabolite concentrations associated with normal exercise (34, 40, 50). …”

Section: Subtypes Of Group Iii/iv Muscle Afferents: Critical Considermentioning

confidence: 99%

“…The recent recognition of functional and structural differences between metaboreceptors and metabo-nociceptors (17, 30, 34, 40, 45, 50) suggests that PECO or hypertonic saline infusions may no longer be considered optimal techniques for investigating the role of those group III/IV muscle afferents which are active during normal, freely perfused exercise of light to strenuous intensity (i.e. ergoreceptors) on circulation, ventilation and central fatigue.…”

Section: Subtypes Of Group Iii/iv Muscle Afferents: Critical Considermentioning

confidence: 99%

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Autonomic responses to exercise: Group III/IV muscle afferents and fatigue

Amann

Sidhu

Weavil

et al. 2015

Autonomic Neuroscience

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151

115

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Group III and IV muscle afferents originating in exercising limb muscle play a significant role in the development of fatigue during exercise in humans. Feedback from these sensory neurons to the central nervous system (CNS) reflexively increases ventilation and central (cardiac output) and peripheral (limb blood flow) hemodynamic responses during exercise and thereby assures adequate muscle blood flow and O2 delivery. This response depicts a key factor in minimizing the rate of development of peripheral fatigue and in optimizing aerobic exercise capacity. On the other hand, the central projection of group III/IV muscle afferents impairs performance and limits the exercising human via its diminishing effect on the output from spinal motoneurons which decreases voluntary muscle activation (i.e. facilitates central fatigue). Accumulating evidence from recent animal studies suggests the existence of two subtypes of group III/IV muscle afferents. While one subtype only responds to physiological and innocuous levels of endogenous intramuscular metabolites (lactate, ATP, protons) associated with ‘normal’, predominantly aerobic exercise, the other subtype only responds to higher and concurrently noxious levels of metabolites present in muscle during ischaemic contractions or following, for example, hypertonic saline infusions. This review discusses the mechanisms through which group III/IV muscle afferent feedback mediates both central and peripheral fatigue in exercising humans. We also briefly summarize accumulating evidence from recent animal and human studies documenting the existence of two subtypes of group III/IV muscle afferents and the relevance of this discovery for the interpretation of previous work and the design of future studies.

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Exogenously applied muscle metabolites synergistically evoke sensations of muscle fatigue and pain in human subjects

Cited by 191 publications

References 69 publications

Fibromyalgia: A Critical and Comprehensive Review

Fibromyalgia: A Critical and Comprehensive Review

Autonomic Adjustments to Exercise in Humans

Autonomic responses to exercise: Group III/IV muscle afferents and fatigue

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