Plasticity of TRPV1-Expressing Sensory Neurons Mediating Autonomic Dysreflexia Following Spinal Cord Injury

Ramer, Leanne M.; Stolk, Arjen; Inskip, Jessica A.; Ramer, Matt S.; Krassioukov, Andrei V.

doi:10.3389/fphys.2012.00257

Cited by 56 publications

(38 citation statements)

References 89 publications

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“…22,23 It was shown that in the acute period post SCI, AD is typically less developed, and over time, as plastic changes within the spinal cord and aberrant inappropriate connections within the central and peripheral nervous system are established, AD becomes more prominent. 24 We also have to acknowledge a few limitations of this study. There are only 21 subjects included in this study and thus we are cognizant of the limitations of our analysis with respect to duration of effect of injury on the severity of AD.…”

Section: Discussionmentioning

confidence: 99%

Autonomic dysreflexia severity during urodynamics and cystoscopy in individuals with spinal cord injury

Liu

Fougere

et al. 2013

Spinal Cord

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Study Design: Retrospective chart review. Objective: To compare autonomic dysreflexia (AD) severity during urodynamics and cystoscopy in individuals with spinal cord injury (SCI). Setting: Outpatient urological clinic. Methods: Demographic and clinical data were collected from charts of individuals with SCI who had blood pressure (BP) monitoring during urological procedures. Cardiovascular parameters were collected at baseline and during the various stages of two examinations. Results: A total of 21 SCI individuals (mean age 49.4 years) who underwent both procedures developed episodes of AD. The majority of individuals had cervical SCI (85.7%). The median duration of injury was 183 months (ranging from 3 to 530 months). There was statistically more of an increase (P ¼ 0.039) in systolic BP during cystoscopy (67.1 ± 33.8 mm Hg) in comparison with urodynamics (51.8±21.8 mm Hg). The BP response during episodes of AD was more pronounced in individuals with more than 2 years post SCI than with less than 2 years post SCI during both urodynamics and cystoscopy (P ¼ 0.047 and P ¼ 0.010, respectively). Conclusion: Even though cystoscopy filled the bladder to lesser volumes than did urodynamics (150 ml vs 500 ml), during cystoscopy the individuals developed greater changes in systolic BP, indicating that stimulation of the urethra/prostate/internal sphincter region probably is a more potent stimulus of AD than just the filling of the bladder. The severity of AD also increased with time post SCI during both procedures. Considering the high incidence of silent episodes of AD during the urological procedures, it is recommended that monitoring of cardiovascular parameters during these procedures be routinely performed. One of the most common physician-induced causes of AD in individuals with SCI is the use of procedures that involve urinary bladder and urogenital areas. 3 Previously, numerous studies using different groups of individuals with SCI examined CV responses either during urodynamic 3-6 or cystoscopic examination. 7,8 These two procedures both involve urinary bladder distension. However, cystoscopy includes greater stimulation of the urethra and bladder neck afferents during the procedure through urethral/prostate/ internal sphincter passage and dilation, which could then provide more intense afferent stimulation to the spinal cord and trigger more pronounced episodes of AD. Considering the physiological difference

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Section: Discussionmentioning

confidence: 99%

Autonomic dysreflexia severity during urodynamics and cystoscopy in individuals with spinal cord injury

Liu

Fougere

et al. 2013

Spinal Cord

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“…6,14,16 Also, it has been documented that AD induced by colorectal distention is mediated by C-fiber afferent pathways in SCI rats. 17 The present study further revealed that TRPV1 channel-expressing C-fiber bladder afferents are responsible for SCI-associated AD during bladder distention because the enhanced bladder-to-vascular reflex induced by bladder distention in SCI rats was significantly reduced by RTXinduced C-fiber desensitization. Although various mediators could contribute to afferent hyperexcitability after SCI, neurotrophic factors such as NGF released within the urinary bladder or the spinal cord reportedly have an important role in SCI-induced neuroplasticity.…”

Section: Autonomic Dysreflexia In Spinal Cord Injured Ratsmentioning

confidence: 68%

Mechanisms inducing autonomic dysreflexia during urinary bladder distention in rats with spinal cord injury

et al. 2014

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Objectives: This study investigated the mechanisms inducing autonomic dysreflexia due to enhanced bladder-to-vascular reflexes in rats with spinal cord injury (SCI). Methods: SCI was produced by the transection of the Th4-5 spinal cord in female Sprague-Dawley rats. At 4 weeks after SCI, changes in blood pressure during graded increases in intravesical pressure (20-60 cm H 2 O) were measured in spinal-intact (SI) and SCI rats under urethane anesthesia. In five animals, effects of C-fiber desensitization induced by intravesical application of resiniferatoxin (RTX), a TRPV1 agonist, on the bladder-to-vascular reflex were also examined. Nerve growth factor (NGF) levels of mucosa and detrusor muscle layers of the bladder were measured by enzyme-linked immunosorbent assay. The expression levels of TRPV1 and TRPA1 channels were also examined in laser captured bladder afferent neurons obtained from L6 DRG, which were labeled by DiI injected into the bladder wall. Results: In SI and SCI rats, systemic arterial blood pressure was increased in a pressure-dependent manner during increases in the intravesical pressure, with significantly higher blood pressure elevation at the intravesical pressure of 20 cm H 2 O in SCI rats vs SI rats. The arterial blood pressure responses to bladder distention were significantly reduced by RTX-induced desensitization of C-fiber bladder afferent pathways. SCI rats had higher NGF protein levels in the bladder and higher TRPV1 and TRPA1 mRNA levels in bladder afferent neurons compared with SI rats. Conclusions: The bladder-to-vascular reflex induced by TRPV1-expressing C-fiber afferents during bladder distention is enhanced after SCI in association with increased expression of NGF in the bladder and TRP channels in bladder afferent neurons. The most common source of stimulation that initiates AD is the genitourinary tract including bladder distention, followed by colorectal distention. 1 It has been shown that vascular responses (that is, hypertension) induced by bladder distention are mediated by the activation of TRPV1 (capsaicin receptor)-expressing C-fiber bladder afferent pathways in spinal-intact (SI) rats. 3 In addition, the expression of TRP channels such as TRPV1 and TRPA1 are involved in the sensitization of C-fiber afferent pathways. 4 Previous studies have also indicated that increased levels of nerve growth factor (NGF) in the bladder is one of the key mediators to induce hyperexcitability of C-fiber bladder afferent pathways after SCI, resulting in detrusor overactivity (DO), [5][6][7][8] and that intrathecal application of NGF antibodies, which reduces NGF levels in bladder afferent pathways, is effective for DO as well as AD in SCI rats. [9][10][11] A recent study demonstrated that the intravesical treatment with botulinum toxin also reduces AD induced

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“…18 Recent data from animal studies suggest that TRPV1 (transient receptor potential vanilloid 1)-mediated stimuli from the colorectum are involved in conveying the stimuli that trigger episodes of AD. 19 Axons of the sensory neurons from the thoracolumbar and lumbosacral dorsal root ganglia expressing TRPA1 (transient receptor potential ankyrin 1) are present in the pelvic nerves that reach the distal colon. 20 It is believed that TRPV1 neurons are involved in the regulation of colonic motor function, but usually not in nociception.…”

Section: Discussionmentioning

confidence: 99%

Autonomic dysreflexia during bowel evacuation procedures and bladder filling in subjects with spinal cord injury

et al. 2014

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Study design: Randomized, controlled clinical trial. Objectives: Bladder and bowel management may cause serious autonomic dysreflexia (AD) in subjects with high spinal cord injury (SCI). We aimed at investigating autonomic responses to digital rectal evacuation (DE), transanal irrigation (TAI) with 500 ml and filling cystometry (FC) in SCI. Setting: Aarhus University Hospital, Denmark. Methods: Eight subjects with SCI (AIS A) at or above T6 (high SCI) and a previous history of AD were compared with three subjects with SCI (AIS A) between T10 and L2 (low SCI). In randomized order, DE, TAI and FC were performed. AD was defined as an acute rise in systolic blood pressure (sBP) of X30 mm Hg above baseline. Blood levels of norepinephrine and epinephrine were determined before and shortly after the procedures. Results: During all three procedures, AD occurred in all patients with high SCI but not in those with low SCI. In high SCI subjects, DE increased median sBP from 127 (range: 86-154) to 188 (range: 140-206) mm Hg (Po0.02), TAI from 126 (range: 91-146) to 163 (range: 130-188) mm Hg (Po0.02) and FC from 125 (range: 106-149) to 200 (range: 179-220) mm Hg (Po0.01). The sBP increase was lower during TAI than during DE (Po0.05) or FC (Po0.02). In high SCI subjects, the blood levels of norepinephrine, but not those of epinephrine, increased significantly during all three stimuli (all Po0.05). Conclusion: Bowel and bladder management caused AD in high SCI. The response is less severe during TAI than during FC or DE.

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Plasticity of TRPV1-Expressing Sensory Neurons Mediating Autonomic Dysreflexia Following Spinal Cord Injury

Cited by 56 publications

References 89 publications

Autonomic dysreflexia severity during urodynamics and cystoscopy in individuals with spinal cord injury

Autonomic dysreflexia severity during urodynamics and cystoscopy in individuals with spinal cord injury

Mechanisms inducing autonomic dysreflexia during urinary bladder distention in rats with spinal cord injury

Autonomic dysreflexia during bowel evacuation procedures and bladder filling in subjects with spinal cord injury

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