Motor activity induces release of serotonin in the dorsal horn of the rat lumbar spinal cord

Gerin, Christine; Teilhac, J.-R.; Smith, Kristin; Privat, Alain

doi:10.1016/j.neulet.2008.01.081

Cited by 26 publications

(21 citation statements)

References 16 publications

(50 reference statements)

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“…The serotonergic system modulates both nociceptive and motor spinal cord circuits, 28,31,32,39,45,52,57 and motor activity increases the release of serotonin within spinal and supraspinal areas parallel to reduction of mechanical hyperalgesia. 29,33 Moreover, physical exercise decreases NKCC1 levels and restores KCC2 along with recovery of inhibitory reflex responses in spinal cord injured rats. 14 We suggest that the increased activity induced by our treadmill protocol may act similarly by upregulating serotonin activity and may stimulate PKC to restore KCC2-dependent disinhibition to pain after peripheral nerve injury.…”

Section: Possible Role Of Descending Pathwaysmentioning

confidence: 99%

Early increasing-intensity treadmill exercise reduces neuropathic pain by preventing nociceptor collateral sprouting and disruption of chloride cotransporters homeostasis after peripheral nerve injury

López-Alvarez

Mòdol²,

Navarro³

et al. 2015

Pain

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Activity treatments, such as treadmill exercise, are used to improve functional recovery after nerve injury, parallel to an increase in neurotrophin levels. However, despite their role in neuronal survival and regeneration, neurotrophins may cause neuronal hyperexcitability that triggers neuropathic pain. In this work, we demonstrate that an early increasing-intensity treadmill exercise (iTR), performed during the first week (iTR1) or during the first 2 weeks (iTR2) after section and suture repair of the rat sciatic nerve, significantly reduced the hyperalgesia developing rapidly in the saphenous nerve territory and later in the sciatic nerve territory after regeneration. Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) expression in sensory neurons and spinal cord was reduced in parallel. iTR prevented the extension of collateral sprouts of saphenous nociceptive calcitonin gene-related peptide fibers within the adjacent denervated skin and reduced NGF expression in the same skin and in the L3 dorsal root ganglia (DRG). Injury also induced Na⁺-K⁺-2Cl⁻ cotransporter 1 (NKCC1) upregulation in DRG, and K⁺-Cl⁻ cotransporter 2 (KCC2) downregulation in lumbar spinal cord dorsal horn. iTR normalized NKCC1 and boosted KCC2 expression, together with a significant reduction of microgliosis in L3-L5 dorsal horn, and a reduction of BDNF expression in microglia at 1 to 2 weeks postinjury. These data demonstrate that specific activity protocols, such as iTR, can modulate neurotrophins expression after peripheral nerve injury and prevent neuropathic pain by blocking early mechanisms of sensitization such as collateral sprouting and NKCC1/KCC2 disregulation.

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Section: Possible Role Of Descending Pathwaysmentioning

confidence: 99%

Early increasing-intensity treadmill exercise reduces neuropathic pain by preventing nociceptor collateral sprouting and disruption of chloride cotransporters homeostasis after peripheral nerve injury

López-Alvarez

Mòdol²,

Navarro³

et al. 2015

Pain

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“…99 Treadmill stepping for 60 min has also led to increases of serotonin (5-HT) in laminae III-V, possibly from activation of the nucleus raphe magnus during motor training. 100 Serotonergic neurons in certain brainstem nuclei project to the dorsal horn, 101 and decreases in serotoninpositive fibers below the level of SCI are associated with neuropathic pain; intrathecal delivery of 5HT can attenuate allodynia. 102 Engesser-Cessar and colleagues 103 showed that wheel running in SCI mice led to an improvement in locomotion as well as an increase in serotonin-positive fibers below the level of the injury.…”

Section: Figmentioning

confidence: 99%

Novel Multi-System Functional Gains via Task Specific Training in Spinal Cord Injured Male Rats

Ward

Herrity

Smith

et al. 2014

Journal of Neurotrauma

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Locomotor training (LT) after spinal cord injury (SCI) is a rehabilitative therapy used to enhance locomotor recovery. There is evidence, primarily anecdotal, also associating LT with improvements in bladder function and reduction in some types of SCI-related pain. In the present study, we determined if a step training paradigm could improve outcome measures of locomotion, bladder function, and pain/allodynia. After a T10 contusive SCI trained animals (adult male Wistar rats), trained animals began quadrupedal step training beginning 2 weeks post-SCI for 1 h/day. End of study experiments (3 months of training) revealed significant changes in limb kinematics, gait, and hindlimb flexor-extensor bursting patterns relative to non-trained controls. Importantly, micturition function, evaluated with terminal transvesical cystometry, was significantly improved in the step trained group (increased voiding efficiency, intercontraction interval, and contraction amplitude). Because both SCI and LT affect neurotrophin signaling, and neurotrophins are involved with post-SCI plasticity in micturition pathways, we measured bladder neurotrophin mRNA. Training regulated the expression of nerve growth factor (NGF) but not BDNF or NT3. Bladder NGF mRNA levels were inversely related to bladder function in the trained group. Monitoring of overground locomotion and neuropathic pain throughout the study revealed significant improvements, beginning after 3 weeks of training, which in both cases remained consistent for the study duration. These novel findings, improving non-locomotor in addition to locomotor functions, demonstrate that step training post-SCI could contribute to multiple quality of life gains, targeting patient-centered high priority deficits.

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“…Although there are many studies considering serotonin in nociceptive [22][23][24][25] and motor [26][27][28] modulations, and exercise-induced analgesia [5,6,8,10,29,30], it is important to demonstrate the possible changes to the spinal and supraspinal serotonergic nerve activity in animals submitted to peripheral nervous lesion combined with aerobic exercise training. Thus, this study investigated the effects of aerobic treadmill exercise training on serotonin immunoreactivity patterns in magnus and dorsal raphe nuclei and lumbosacral spinal cord of rats submitted to sciatic nerve transection.…”

Section: Introductionmentioning

confidence: 99%

Effect of Treadmill Exercise on Serotonin Immunoreactivity in Medullary Raphe Nuclei and Spinal Cord Following Sciatic Nerve Transection in Rats

et al. 2009

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The serotoninergic system modulates nociceptive and locomotor spinal cord circuits. Exercise improves motor function and changes dopaminergic, noradrenergic, and serotonergic central systems. However, the direct relationship between serotonin, peripheral nerve lesion and aerobic treadmill exercise has not been studied. Using immunohistochemistry and optic densitometry, this study showed that the sciatic nerve transection increased the serotoninergic immunoreactivity in neuronal cytoplasm of the magnus raphe nuclei of trained and sedentary rats. In the dorsal raphe nucleus the increase only occurred in sedentary-sham-operated rats. In the spinal cord of trained, transected rats, the ventral horn showed significant changes, while the change in dorsal horn was insignificant. Von Frey's test indicated analgesia in all exercise-trained rats. The sciatic nerve functional index indicated recovery in the trained group. Thus, both the aerobic treadmill exercise training and the nervous lesion appear to contribute to changes in serotonin immunoreactivity.

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Motor activity induces release of serotonin in the dorsal horn of the rat lumbar spinal cord

Cited by 26 publications

References 16 publications

Early increasing-intensity treadmill exercise reduces neuropathic pain by preventing nociceptor collateral sprouting and disruption of chloride cotransporters homeostasis after peripheral nerve injury

Early increasing-intensity treadmill exercise reduces neuropathic pain by preventing nociceptor collateral sprouting and disruption of chloride cotransporters homeostasis after peripheral nerve injury

Novel Multi-System Functional Gains via Task Specific Training in Spinal Cord Injured Male Rats

Effect of Treadmill Exercise on Serotonin Immunoreactivity in Medullary Raphe Nuclei and Spinal Cord Following Sciatic Nerve Transection in Rats

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