Persistent Pain after Spinal Cord Injury Is Maintained by Primary Afferent Activity

The primary afferent neurotransmitter triggering the spinal micturition reflex after complete spinal cord injury (SCI) in the rat is unknown. Substance P detected immunohistochemically in the sacral parasympathetic nucleus was significantly higher in 12 SCI rats than in 12 spinally intact rats ( P = 0.008), suggesting substance P as a plausible candidate for the primary afferent neurotransmitter. The effects of the tachykinin NK1 receptor antagonist L-733060 on the spinal micturition reflex were then determined by performing conscious cystometry in an additional 14 intact rats and 14 SCI rats with L-733060 (0.1–100 μg) administered intrathecally at L6-S1. L-733060 was without effect in intact rats, but blocked the spinal micturition reflex in 10 of 14 SCI rats and increased the intermicturition interval in 2 of 4 others at doses ranging from 10 to 100 μg. Both phasic and nonphasic voiding contractions, differentiated according to the presence of phasic external urethral sphincter (EUS) activity, were present in most SCI rats. Both types of contractions were blocked by high doses of L-733060. Interestingly, there was a relative decline in phasic voiding contractions at high doses as well as a decline in contraction amplitude in nonphasic voiding contractions. In other respects, cystometric variables were largely unaffected in either spinally intact or SCI rats. L-733060 did not affect tonic EUS activity at any dose except when the spinal micturition reflex was blocked and tonic activity was consequently lost. These experiments show that tachykinin action at spinal NK1 receptors plays a major role in the spinal micturition reflex in SCI rats.

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PI3K Mediated Activation of GSK-3β Reduces At-Level Primary Afferent Growth Responses Associated with Excitotoxic Spinal Cord Injury Dysesthesias

Molecular Pain ◽

10.1186/s12990-015-0041-2 ◽

2015 ◽

Vol 11 ◽

pp. s12990-015-0041 ◽

Cited By ~ 4

Author(s):

Sonja K Bareiss ◽

Elizabeth Dugan ◽

Kori L Brewer

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Growth Responses ◽

Primary Afferent ◽

Cord Injury ◽

Gsk 3Β

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Direct evidence of primary afferent sprouting in distant segments following spinal cord injury in the rat: colocalization of GAP-43 and CGRP

Experimental Neurology ◽

10.1016/s0014-4886(03)00364-9 ◽

2003 ◽

Cited By ~ 1

Author(s):

A Ondarza

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Direct Evidence ◽

Primary Afferent ◽

Cord Injury

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Moxibustion attenuates neurogenic detrusor overactivity in spinal cord injury rats by inhibiting M2/ATP/P2X3 pathway

10.21203/rs.3.rs-616482/v1 ◽

2021 ◽

Author(s):

Lu Wang ◽

Yuan-Bo Fu ◽

Yi Liu ◽

Na-Na Yang ◽

Si-Ming Ma ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Detrusor Overactivity ◽

Bladder Function ◽

Potential Candidate ◽

Neurogenic Detrusor Overactivity ◽

Afferent Activity ◽

Sprague Dawley ◽

Pressure Threshold ◽

Cord Injury

Abstract Background Activation of muscarinic receptors located in bladder sensory pathways is generally considered to be the primary contributor for driving the pathogenesis of neurogenic detrusor overactivity following spinal cord injury. The present study is undertaken to examine whether moxibustion improves neurogenic detrusor overactivity via modulating the abnormal muscarinic receptor pathway. Methods Female Sprague-Dawley rats were subjected to spinal cord injury with T9-10 spinal cord transection. Fourteen days later, animals were received moxibustion treatment for one week. Urodynamic parameters and pelvic afferents discharge were measured. Acetylcholine and adenosine triphosphate content in the voided cystometry fluid were determined. Expressions of M2, M3 and P2X3 receptor in the bladder mucosa were evaluated. Results Moxibustion treatment prevented the development of detrusor overactivity in SCI rats, with an increase in the intercontraction interval and micturition pressure threshold and a decrease in afferent activity during filling. The expression of M2, but not M3, was markedly suppressed by moxibustion, accompanied by a reduction in the level of ATP and P2X3. M2 receptor antagonist methoctramine hemihydrate had similar effects to moxibustion on bladder function and afferent activity, while the M2-preferential agonist oxotremorine methiodide abolished the beneficial effects of moxibustion. Conclusions Moxibustion is a potential candidate for treatment of neurogenic bladder overactivity in a rat model of spinal cord injury possibly through inhibiting the M2/ATP/P2X3 pathway.

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Plasticity in Cervical Motor Circuits following Spinal Cord Injury and Rehabilitation

Biology ◽

10.3390/biology10100976 ◽

2021 ◽

Vol 10 (10) ◽

pp. 976

Author(s):

John R. Walker ◽

Megan Ryan Detloff

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Nervous System ◽

Cervical Spinal Cord ◽

Long Term Potentiation ◽

Background Information ◽

Primary Afferent ◽

Functional Connections ◽

Cord Injury ◽

The Impact

Neuroplasticity is a robust mechanism by which the central nervous system attempts to adapt to a structural or chemical disruption of functional connections between neurons. Mechanical damage from spinal cord injury potentiates via neuroinflammation and can cause aberrant changes in neural circuitry known as maladaptive plasticity. Together, these alterations greatly diminish function and quality of life. This review discusses contemporary efforts to harness neuroplasticity through rehabilitation and neuromodulation to restore function with a focus on motor recovery following cervical spinal cord injury. Background information on the general mechanisms of plasticity and long-term potentiation of the nervous system, most well studied in the learning and memory fields, will be reviewed. Spontaneous plasticity of the nervous system, both maladaptive and during natural recovery following spinal cord injury is outlined to provide a baseline from which rehabilitation builds. Previous research has focused on the impact of descending motor commands in driving spinal plasticity. However, this review focuses on the influence of physical therapy and primary afferent input and interneuron modulation in driving plasticity within the spinal cord. Finally, future directions into previously untargeted primary afferent populations are presented.

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