scholarly journals 5-HT1D receptors inhibit the monosynaptic stretch reflex by modulating C-fiber activity

2019 ◽  
Vol 121 (5) ◽  
pp. 1591-1608 ◽  
Author(s):  
Ana M. Lucas-Osma ◽  
Yaqing Li ◽  
Katie Murray ◽  
Shihao Lin ◽  
Sophie Black ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stretch Reflex ◽  
Spinal Transection ◽  
Dorsal Rhizotomy ◽  
C Fibers ◽  
Cord Injury ◽  
C Fiber ◽  
Receptor Plasticity ◽  
Highly Correlated

The monosynaptic stretch reflex (MSR) plays an important role in feedback control of movement and posture but can also lead to unstable oscillations associated with tremor and clonus, especially when increased with spinal cord injury (SCI). To control the MSR and clonus after SCI, we examined how serotonin regulates the MSR in the sacrocaudal spinal cord of rats with and without a chronic spinal transection. In chronic spinal rats, numerous 5-HT receptor agonists, including zolmitriptan, methylergonovine, and 5-HT, inhibited the MSR with a potency highly correlated to their binding affinity to 5-HT1D receptors and not other 5-HT receptors. Selective 5-HT1D receptor antagonists blocked this agonist-induced inhibition, although antagonists alone had no action, indicating a lack of endogenous or constitutive receptor activity. In normal uninjured rats, the MSR was likewise inhibited by 5-HT, but at much higher doses, indicating a supersensitivity after SCI. This supersensitivity resulted from the loss of the serotonin transporter SERT with spinal transection, because normal and injured rats were equally sensitive to 5-HT after SERT was blocked or to agonists not transported by SERT (zolmitriptan). Immunolabeling revealed that the 5-HT1D receptor was confined to superficial lamina of the dorsal horn, colocalized with CGRP-positive C-fibers, and eliminated by dorsal rhizotomy. 5-HT1D receptor labeling was not found on large proprioceptive afferents or α-motoneurons of the MSR. Thus serotonergic inhibition of the MSR acts indirectly by modulating C-fiber activity, opening up new possibilities for modulating reflex function and clonus via pain-related pathways. NEW & NOTEWORTHY Brain stem-derived serotonin potently inhibits afferent transmission in the monosynaptic stretch reflex. We show that serotonin produces this inhibition exclusively via 5-HT1D receptors, and yet these receptors are paradoxically mostly confined to C-fibers. This suggests that serotonin acts by gating of C-fiber activity, which in turn modulates afferent transmission to motoneurons. We also show that the classic supersensitivity to 5-HT after spinal cord injury results from a loss of SERT, and not 5-HT1D receptor plasticity.

Drastic Decrease in Isoflurane Minimum Alveolar Concentration and Limb Movement Forces after Thoracic Spinal Cooling and Chronic Spinal Transection in Rats

2005 ◽  
Vol 102 (3) ◽  
pp. 624-632 ◽  
Author(s):  
Steven L. Jinks ◽  
Carmen L. Dominguez ◽  
Joseph F. Antognini
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Minimum Alveolar Concentration ◽  
Tail Flick ◽  
Noxious Stimulation ◽  
Partial Recovery ◽  
Spinal Transection ◽  
Thoracic Spinal ◽  
Cord Injury ◽  
Stimulation Of

Background Individuals with spinal cord injury may undergo multiple surgical procedures; however, it is not clear how spinal cord injury affects anesthetic requirements and movement force under anesthesia during both acute and chronic stages of the injury. Methods The authors determined the isoflurane minimum alveolar concentration (MAC) necessary to block movement in response to supramaximal noxious stimulation, as well as tail-flick and hind paw withdrawal latencies, before and up to 28 days after thoracic spinal transection. Tail-flick and hind paw withdrawal latencies were measured in the awake state to test for the presence of spinal shock or hyperreflexia. The authors measured limb forces elicited by noxious mechanical stimulation of a paw or the tail at 28 days after transection. Limb force experiments were also conducted in other animals that received a reversible spinal conduction block by cooling the spinal cord at the level of the eighth thoracic vertebra. Results A large decrease in MAC (to </= 40% of pretransection values) occurred after spinal transection, with partial recovery (to approximately 60% of control) at 14-28 days after transection. Awake tail-flick and hind paw withdrawal latencies were facilitated or unchanged, whereas reflex latencies under isoflurane were depressed or absent. However, at 80-90% of MAC, noxious stimulation of the hind paw elicited ipsilateral limb withdrawals in all animals. Hind limb forces were reduced (by >/= 90%) in both chronic and acute cold-block spinal animals. Conclusions The immobilizing potency of isoflurane increases substantially after spinal transection, despite the absence of a baseline motor depression, or "spinal shock." Therefore, isoflurane MAC is determined by a spinal depressant action, possibly counteracted by a supraspinal facilitatory action. The partial recovery in MAC at later time points suggests that neuronal plasticity after spinal cord injury influences anesthetic requirements.

The tonic stretch reflex and spastic hypertonia after spinal cord injury

2006 ◽  
Vol 174 (2) ◽  
pp. 386-396 ◽  
Author(s):  
Adam J. Woolacott ◽  
John A. Burne
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stretch Reflex ◽  
Cord Injury

Role of dorsal rhizotomy in spinal cord injury–induced spasticity

2014 ◽  
Vol 14 (3) ◽  
pp. 266-270 ◽  
Author(s):  
Renee M. Reynolds ◽  
Ryan P. Morton ◽  
Marion L. Walker ◽  
Teresa L. Massagli ◽  
Samuel R. Browd
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Pediatric Patients ◽  
Selective Dorsal Rhizotomy ◽  
Dorsal Rhizotomy ◽  
The Third ◽  
Oral Medications ◽  
Cord Injury

Selective dorsal rhizotomy may have a role in the management of spinal cord injury (SCI)–induced spasticity. Spasticity and spasms are common sequelae of SCI in children. Depending on the clinical scenario, treatments may include physical and occupational therapy, oral medications, chemodenervation, and neurosurgical interventions. Selective dorsal rhizotomy (SDR) is used in the management of spasticity in selected children with cerebral palsy, but, to the authors' knowledge, its use has not been reported in children with SCI. The authors describe the cases of 3 pediatric patients with SCI and associated spasticity treated with SDR. Two of the 3 patients have had significant long-term improvement in their preoperative spasticity. Although the third patient also experienced initial relief, his spasticity quickly returned to its preoperative severity, necessitating additional therapies. Selective dorsal rhizotomy may have a place in the treatment of selected children with spasticity due to SCI.

scholarly journals Altered activation patterns by triceps surae stretch reflex pathways in acute and chronic spinal cord injury

2011 ◽  
Vol 106 (4) ◽  
pp. 1669-1678 ◽  
Author(s):  
Alain Frigon ◽  
Michael D. Johnson ◽  
C. J. Heckman
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stretch Reflex ◽  
Triceps Surae ◽  
Stretch Reflexes ◽  
Activation Patterns ◽  
Intact State ◽  
Hindlimb Muscles ◽  
Reflex Pathways ◽  
Cord Injury

Spinal reflexes are modified by spinal cord injury (SCI) due the loss of excitatory inputs from supraspinal structures and changes within the spinal cord. The stretch reflex is one of the simplest pathways of the central nervous system and was used presently to evaluate how inputs from primary and secondary muscle spindles interact with spinal circuits before and after spinal transection (i.e., spinalization) in 12 adult decerebrate cats. Seven cats were spinalized and allowed to recover for 1 mo (i.e., chronic spinal state), whereas 5 cats were evaluated before (i.e., intact state) and after acute spinalization (i.e., acute spinal state). Stretch reflexes were evoked by stretching the left triceps surae (TS) muscles. The force evoked by TS muscles was recorded along with the activity of several hindlimb muscles. Stretch reflexes were abolished in the acute spinal state due to an inability to activate TS muscles, such as soleus (Sol) and lateral gastrocnemius (LG). In chronic spinal cats, reflex force had partly recovered but Sol and LG activity remained considerably depressed, despite the fact that injecting clonidine could recruit these muscles during locomotor-like activity. In contrast, other muscles not recruited in the intact state, most notably semitendinosus and sartorius, were strongly activated by stretching TS muscles in chronic spinal cats. Therefore, stretch reflex pathways from TS muscles to multiple hindlimb muscles undergo functional reorganization following spinalization, both acute and chronic. Altered activation patterns by stretch reflex pathways could explain some sensorimotor deficits observed during locomotion and postural corrections after SCI.

Effect of spinal cord injury and its lesion level on stretch reflex modulation by cold stimulation in humans

2011 ◽  
Vol 122 (1) ◽  
pp. 163-170 ◽  
Author(s):  
H. Ogata ◽  
D.G. Sayenko ◽  
E. Yamamoto ◽  
T. Kitamura ◽  
S. Yamamoto ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stretch Reflex ◽  
Reflex Modulation ◽  
Cold Stimulation ◽  
Cord Injury ◽  
Lesion Level

scholarly journals The recovery of standing and locomotion after spinal cord injury does not require task-specific training

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Jonathan Harnie ◽  
Adam Doelman ◽  
Emmanuelle de Vette ◽  
Johannie Audet ◽  
Etienne Desrochers ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Specific Activity ◽  
Weight Bearing ◽  
Triceps Surae ◽  
Full Weight Bearing ◽  
Specific Training ◽  
Spinal Transection ◽  
Cord Injury ◽  
Complete Spinal Cord Injury

After complete spinal cord injury, mammals, including mice, rats and cats, recover hindlimb locomotion with treadmill training. The premise is that sensory cues consistent with locomotion reorganize spinal sensorimotor circuits. Here, we show that hindlimb standing and locomotion recover after spinal transection in cats without task-specific training. Spinal-transected cats recovered full weight bearing standing and locomotion after five weeks of rhythmic manual stimulation of triceps surae muscles (non-specific training) and without any intervention. Moreover, cats modulated locomotor speed and performed split-belt locomotion six weeks after spinal transection, functions that were not trained or tested in the weeks prior. This indicates that spinal networks controlling standing and locomotion and their interactions with sensory feedback from the limbs remain largely intact after complete spinal cord injury. We conclude that standing and locomotor recovery is due to the return of neuronal excitability within spinal sensorimotor circuits that do not require task-specific activity-dependent plasticity.

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