The Capsaicin-Sensitive Afferent Neuron in Skeletal Muscle Is Abnormal in Heart Failure

Smith, Scott A.; Williams, Maurice A.; Mitchell, Jere H.; Mammen, Pradeep P.A.; Garry, Mary G.

doi:10.1161/01.cir.0000162473.10951.0a

Cited by 86 publications

(139 citation statements)

References 40 publications

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“…Mizumura and Kumazawa 42) also showed that nociceptive chemical stimulations to thin muscle afferents, that are assumed to be polymodal receptors in dogs, induced a significant increase in ventilation. These results support the physiological concept 51,52) that at least some pain receptors (nociceptors) contribute to peripheral afferent feedback in cardiovascular and respiratory responses to exercise in animals. The present findings in human studies also support the idea that at least some thin muscle afferents are relevant to dual modulation of pain sensation as pain receptors and respiratory reflex during exercise as ergoreceptors.…”

Section: Physiological Implicationssupporting

confidence: 88%

“…These fibers are classified as pain receptors (nociceptors) and ergoreceptors, which contribute to the reflex modulation of ventilatory and cardiovascular responses to muscular exercise. Since primary afferent nociceptive neurons have polymodal characteristics 50) , it has not been fully clarified whether or not thin muscle afferents contribute to both peripheral afferent feedback in ventilatory drive during exercise and the perception of pain 51,52) . Smith et al 52) revealed that the abolition of capsaicinsensitive fibers, which play a role in nociceptors, caused a significant abnormality in the cardiovascular response to both muscle contraction and stretching in rats.…”

Section: Physiological Implicationsmentioning

confidence: 99%

“…Since primary afferent nociceptive neurons have polymodal characteristics 50) , it has not been fully clarified whether or not thin muscle afferents contribute to both peripheral afferent feedback in ventilatory drive during exercise and the perception of pain 51,52) . Smith et al 52) revealed that the abolition of capsaicinsensitive fibers, which play a role in nociceptors, caused a significant abnormality in the cardiovascular response to both muscle contraction and stretching in rats. Queme et al 53) demonstrated that inhibition of ADP-responsive P2Y1 receptors, which are related to ischemic pain, not only prevented the increase in mean blood pressure after exercise, but also significantly reduced alterations in painrelated behavior in mice.…”

Section: Physiological Implicationsmentioning

confidence: 99%

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Mechanism and implications of hyperpnea exaggeration at the onset of exercise in mechanical hyperalgesia after eccentric exercise

Hotta

Ishida

2018

JPFSM

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The ventilatory response to moderate-intensity step load exercise has three temporal phases: an initial rapidly increasing phase I, followed by a slower exponential phase II, that leads to the steady state phase III. In muscles with mechanical hyperalgesia (delayed onset muscle soreness) and/or muscle damage a few days after eccentric exercise (ECC), an interesting phenomenon of increased ventilatory response at phases II and III during constant-load exercise and incremental exercise has been reported. However, the mechanisms behind this phenomenon have not been clarified. At least a neural mechanism is partly responsible for this phenomenon because the ventilatory response at neurally modulated phase I has been shown to be exaggerated 2 days after ECC (D2). In the present review, we focus on our previous work to identify the potential mechanism underlying the exaggerated modulation in phase I ventilatory response at D2, in which ECC-induced muscle pain is assumed to be at the peak. We also discuss the physiological and practical implications of this phenomenon.

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Section: Physiological Implicationssupporting

confidence: 88%

Section: Physiological Implicationsmentioning

confidence: 99%

Section: Physiological Implicationsmentioning

confidence: 99%

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Mechanism and implications of hyperpnea exaggeration at the onset of exercise in mechanical hyperalgesia after eccentric exercise

Hotta

Ishida

2018

JPFSM

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“…It was reported that isolated activation of muscle metaboreflex by postexercise circulatory occlusion of the exercising limb resulted in less elevation of muscle SNA (36,47) and less renal vasoconstriction (30,31) in CHF patients than in healthy subjects, whereas the muscle mechanoreflex activation due to passive stretch or involuntary contraction of skeletal muscles evoked greater elevation of muscle SNA (29) and greater renal vasoconstriction (30,34) in CHF patients. Recent studies that used a decerebrated rat model have also shown muscle metaboreflex desensitization (26,46) and muscle mechanoreflex sensitization (26,44,45) in myocardial infarction (MI) animals. These findings suggest that the sensitized muscle mechanoreflex elicits the exaggerated sympathetic activation and contributes to the excess peripheral vasoconstriction during exercise in CHF.…”

mentioning

confidence: 99%

Sympathetic responses to exercise in myocardial infarction rats: a role of central command

Koba¹,

Gao²,

Xing³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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Koba, Satoshi, Zhaohui Gao, Jihong Xing, Lawrence I Sinoway, and Jianhua Li. Sympathetic responses to exercise in myocardial infarction rats: a role of central command. Am J Physiol Heart Circ Physiol 291: H2735-H2742, 2006. First published July 14, 2006 doi:10.1152/ajpheart.00522.2006.-In congestive heart failure (CHF), exaggerated sympathetic activation is observed during exercise, which elicits excess peripheral vasoconstriction. The mechanisms causing this abnormality are not fully understood. Central command is a central neural process that induces parallel activation of motor and cardiovascular systems. This study was undertaken to determine whether central command serves as a mechanism that contributes to the exaggerated sympathetic response to exercise in CHF. In decerebrated rats, renal and lumbar sympathetic nerve responses (RSNA and LSNA, respectively) to 30 s of fictive locomotion were examined. The fictive locomotion was induced by electrical stimulation of the mesencephalic locomotor region (MLR). The study was performed in control animals (fractional shortening Ͼ 40%) and animals with myocardial infarctions (MI; fractional shortening Ͻ 30%). With low stimulation of the MLR (current intensity ϭ 20 A), the sympathetic responses were not significantly different in the control (RSNA: ϩ18 Ϯ 4%; LSNA: ϩ3 Ϯ 2%) and MI rats (RSNA: ϩ16 Ϯ 5%; LSNA: ϩ8 Ϯ 3%). With intense stimulation of the MLR (50 A), the responses were significantly greater in MI rats (RSNA: ϩ127 Ϯ 15%; LSNA: ϩ57 Ϯ 10%) than in the control rats (RSNA: ϩ62 Ϯ 5%; LSNA: ϩ21 Ϯ 6%). In this study, the data demonstrate that RSNA and LSNA responses to intense stimulation of the MLR are exaggerated in MI rats. We suggest that intense activation of central command may play a role in evoking exaggerated sympathetic activation and inducing excessive peripheral vasoconstriction during exercise in CHF.congestive heart failure; mesencephalic locomotor region; renal sympathetic nerve activity; lumbar sympathetic nerve activity EXERCISE ACTIVATES THE SYMPATHETIC nervous system, increases blood pressure, and leads to an increase in blood flow to exercising skeletal muscle. This increase in muscle blood flow is associated with reduced renal blood flow (23). Two principal neural mechanisms are proposed to increase sympathetic nerve activity (SNA) and regulate the cardiovascular system during exercise. These are termed the exercise pressor reflex and central command. The exercise pressor reflex is a neural reflex that arises from receptors sensitive to mechanical and metabolic stimuli in exercising skeletal muscles and stimulates the medulla through the muscle thin afferent fibers (18). Central command is a feed-forward neural mechanism that induces parallel activation of motor and cardiovascular systems (9, 50). The brain sites that generate motor signals also send descending projections to sympathetic neurons (19,20,22).Congestive heart failure (CHF) includes abnormal cardiovascular regulation in exercise. Specifically, sympathetic tone to muscle is elevat...

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“…Li and colleagues 70) provided rat data demonstrating that the pressor response to injection into the arterial supply of hindlimb of capsaicin, a stimulant of vanilloid receptor subtype 1 (VR1) dominantly located on unmyelinated group IV afferents, was attenuated in rats with HF compared to healthy controls. In order to uncover the mechanisms underlying the attenuated metaboreflex in HF, Smith and colleagues 81) performed sets of experiments. First, the effect of selective withdrawal of group IV afferents on EPR response was examined.…”

Section: Contribution Of Rat Studies To Understanding Of Mechanisms Umentioning

confidence: 99%

Exercise pressor reflex in health and diseases: Animal studies

Koba

2015

JPFSM

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A reflex originating in exercising skeletal muscle contributes to sympathoexcitation during exercise. This muscle-based reflex is termed the exercise pressor reflex (EPR). In this review, mechanisms underlying activation of the EPR are examined based on findings mainly obtained from cat studies. Specifically, roles played by chemical and mechanical stimuli due to contraction in increasing discharges of muscle afferent fibers are discussed. Roles metabolic byproducts play in stimulating and sensitizing muscle afferents are also examined. Central cardiovascular sites involved in activation of the EPR are investigated. In this review, moreover, mechanisms by which the EPR function becomes abnormal in heart failure and hypertension are discussed on the basis of experimental data mainly provided by rat studies. In heart failure, the muscle metaboreflex is attenuated while the mechanoreflex is enhanced. In hypertension, both the muscle metabo-and mechano-reflexes are enhanced. Peripheral factors leading to EPR dysfunction in these pathological conditions are examined.

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The Capsaicin-Sensitive Afferent Neuron in Skeletal Muscle Is Abnormal in Heart Failure

Cited by 86 publications

References 40 publications

Mechanism and implications of hyperpnea exaggeration at the onset of exercise in mechanical hyperalgesia after eccentric exercise

Mechanism and implications of hyperpnea exaggeration at the onset of exercise in mechanical hyperalgesia after eccentric exercise

Sympathetic responses to exercise in myocardial infarction rats: a role of central command

Exercise pressor reflex in health and diseases: Animal studies

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