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c-fos expression and NADPH-d reactivity in spinal neurons after fatiguing stimulation of hindlimb muscles in the rat
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
Centre for Musculoskeletal Research, National Institute for Working Life - Umeå.
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2001 (English)In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 923, no 1-2, 91-102 p.Article in journal (Refereed) Published
Abstract [en]

The distribution of Fos-immunoreactive (Fos-ir) and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d)-reactive neurons in the rat lumbar spinal cord was examined following muscle fatigue caused by intermittent high-rate (100 s(-1)) electrical stimulation of the triceps surae muscle or the ventral root L5 (VRL5) for 30 min. Following both types of stimulation, the fatigue-related c-fos gene expression was more extensive in the L2-L5 segments on the stimulated side, and the majority of Fos-ir neurons were concentrated in the dorsal horn. After direct muscle stimulation, the highest number of Fos-ir neurons were detected in two regions: layer 5, and superficial layers (1 and 2(o)), although many labeled cells were also found in layers 3, 4, 6, and 7. In response to VRL5 stimulation, the maximal density of Fos-ir neurons was detected in the middle and lateral parts of layers 1 and 2(o), the zone of termination of high-threshold muscle afferents(.) Statistically significant prevalence of Fos-ir cell number was also found in layers 5 and 7 on the stimulated side. A few Fos-ir neurons were detected in the ventral horn (layer 8 and area 10) on both sides. The lamellar distribution of NADPH-d-reactive neurons was similar over all experimental groups of animals. In the L3-L6 segments, such reactive cells were arranged in two distinct regions: dorsal horn (layers 2(i), 3, and 5) and area 10; in the L1 and L2 segments, an additional cluster of NADPH-d positive cells was found in the intermediolateral cell column (IML). Double-labeled cells were not detected. We suggest that c-fos expression in response to muscle fatigue reveals activity of functionally different types of spinal neurons which could operate together with NOS-containing cells in pre-motoneuronal networks to modulate the motoneuron output.

Place, publisher, year, edition, pages
2001. Vol. 923, no 1-2, 91-102 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:umu:diva-4150DOI: 10.1016/S0006-8993(01)03049-9PubMedID: 11743976OAI: diva2:143132
Available from: 2004-10-08 Created: 2004-10-08 Last updated: 2010-06-28Bibliographically approved
In thesis
1. Experimental studies of spinal mechanisms associated with muscle fatigue
Open this publication in new window or tab >>Experimental studies of spinal mechanisms associated with muscle fatigue
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Muscle fatigue is ubiquitous in every day life.Muscle fatigue might be considered as an altered state of motor behaviour, which impairs motor performance. By contrast, muscle fatigue could also be considered a positive phenomenon, which protects muscle tissue from damage that might be incurred to it by overuse.

The principal aim of the thesis was to explore some of the mechanisms of muscle fatigue at the spinal level in animal models.The activation of multiple motor units of a single calf muscle may influence contractile properties of its neighbouring, otherwise inactive units, providing evidence for spatial spreading of fatigue between different muscle parts. The release of metabolites, their action on inactive muscle units and the effects of local hypoxia are the most likely causes. Fatigue-induced metabolite shift in the interstitium provokes excitation and/or sensitisation of high-threshold afferent fibers, with complex effects on the spinal premotoneuronal network involved in the modulation of motoneuronal output. This was examined by studing the intrasegmental lamellar distribution of the lumbar spinal interneurons following fatiguing contractions of the triceps surae muscle. Furthermore, fatigue of calf muscles enhanced the activity of fusimotor neurons to these muscles irrespective of the regime of muscle activity (isometric vs. lengthening) in conditions that simulate locomotion. Altered fusimotor activity, through increased or maintained muscle spindle afferent responsiveness may be advantageous, providing support to the skeletomotor activity and enhanced information about muscle periphery to higher nervous centres. The particular effects of interneuronal network at motor input (presynaptic inhibition system) and output (recurrent inhibition system) stages were then addressed. Fatigue of triceps surae muscle induced a suppression of the monosynaptic reflex. The intensity of presynaptic inhibition increased, while the intensity of recurrent inhibition decreased. Post fatigue-evoked changes in monosynaptic reflexes and presynaptic inhibition indicate the possibility that high-threshold afferents inhibit group Ia terminals pre-synaptically, which would allow fatigue-induced signals from the muscle to reduce the relevance of proprioceptive feedback. Besides intrasegmental, intersegmental spreading of nociceptive signals was explored. Activation of sensory afferents from dorsal neck muscles by capsaicin induces powerful activation of interneurons located in the cervical spinal cord, as well as a widespread activation of cells in lumbar spinal cord segments.

The results confirm the pivotal role of small diameter muscle afferents in the orchestration of segmental responses to fatigue and show complex interactions that may lead to limited accuracy of motor output. They also depict processes that may be related to, and even become precursors of chronic muscle pain.

Umeå University medical dissertations, ISSN 0346-6612 ; 910
muscle fatigue, monosynaptic reflex, presynaptic inhibition, recurrent inhibition, fusimotor system, Fos-immunoreactivity, referral pain
Research subject
urn:nbn:se:umu:diva-332 (URN)91-7305-703-7 (ISBN)
Public defence
2004-11-12, Stora salen, Arbetslivsinstitutet, 13:00
Available from: 2004-10-08 Created: 2004-10-08 Last updated: 2010-06-28Bibliographically approved

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Kalezic, IvanaLjubisavljevic, MilosWindhorst, UweJohansson, Håkan
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