Spontaneous and Stimulus-Evoked Respiratory Rate Elevation Corresponds to Development of Allodynia in Spinal Cord–Injured Rats

Noble, Donald J.; Martin, Karmarcha K; Parvin, Shangrila; Garraway, Sandra M.

doi:10.1089/neu.2018.5936

Cited by 7 publications

(17 citation statements)

References 76 publications

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“…They then received daily 30-min conditioning sessions over the course of 3 days (~31–33 dpo). On each day, animals were administered brush stimulation in their preferred chambers (once/minute for 15 min) delivered over a distance of ~3 cm across the trunk in the caudal-to-rostral direction at a speed of ~1 cm/s, while they were partially restrained in acrylic cylinders (allowing some movement but not 180 degree changes in orientation; Rodent Restrainer, IITC Life Science, Woodland Hills, CA; Noble et al, 2019 ). In the control, non-preferred chambers, mice received pseudo “stimulation” whereby the brush was swept across the abdominal area but made no direct contact, while animals were under similar partial physical restraint (again once/minute for 15 min).…”

Section: Methodsmentioning

confidence: 99%

Pharmacogenetic inhibition of TrkB signaling in adult mice attenuates mechanical hypersensitivity and improves locomotor function after spinal cord injury

Martin

Noble

Parvin

et al. 2022

Front. Cell. Neurosci.

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Brain-derived neurotrophic factor (BDNF) signals through tropomyosin receptor kinase B (TrkB), to exert various types of plasticity. The exact involvement of BDNF and TrkB in neuropathic pain states after spinal cord injury (SCI) remains unresolved. This study utilized transgenic TrkBF616 mice to examine the effect of pharmacogenetic inhibition of TrkB signaling, induced by treatment with 1NM-PP1 (1NMP) in drinking water for 5 days, on formalin-induced inflammatory pain, pain hypersensitivity, and locomotor dysfunction after thoracic spinal contusion. We also examined TrkB, ERK1/2, and pERK1/2 expression in the lumbar spinal cord and trunk skin. The results showed that formalin-induced pain responses were robustly attenuated in 1NMP-treated mice. Weekly assessment of tactile sensitivity with the von Frey test showed that treatment with 1NMP immediately after SCI blocked the development of mechanical hypersensitivity up to 4 weeks post-SCI. Contrastingly, when treatment started 2 weeks after SCI, 1NMP reversibly and partially attenuated hind-paw hypersensitivity. Locomotor scores were significantly improved in the early-treated 1NMP mice compared to late-treated or vehicle-treated SCI mice. 1NMP treatment attenuated SCI-induced increases in TrkB and pERK1/2 levels in the lumbar cord but failed to exert similar effects in the trunk skin. These results suggest that early onset TrkB signaling after SCI contributes to maladaptive plasticity that leads to spinal pain hypersensitivity and impaired locomotor function.

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Section: Methodsmentioning

confidence: 99%

Pharmacogenetic inhibition of TrkB signaling in adult mice attenuates mechanical hypersensitivity and improves locomotor function after spinal cord injury

Martin

Noble

Parvin

et al. 2022

Front. Cell. Neurosci.

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“…Mice were sacrificed one day after T4 and T10 SCI ( n = 2 each) for histological assessment of the lesioned spinal cord. Luxol fast blue and hematoxylin and eosin staining methodologies which examine myelin and general structure of the injured spinal cord were undertaken as we previously described [ 32 ]. We also performed fluorescent histology to assess GFAP expression in the lesioned spinal cord dorsal horn 1 day after T4 and T10, using routinely used methodologies, e.g., [ 8 ].…”

Section: Methodsmentioning

confidence: 99%

Spinal Cord Injury Increases Pro-inflammatory Cytokine Expression in Kidney at Acute and Sub-chronic Stages

et al. 2021

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Abstract— Accumulating evidence supports that spinal cord injury (SCI) produces robust inflammatory plasticity. We previously showed that the pro-inflammatory cytokine tumor necrosis factor (TNF)α is increased in the spinal cord after SCI. SCI also induces a systemic inflammatory response that can impact peripheral organ functions. The kidney plays an important role in maintaining cardiovascular health. However, SCI-induced inflammatory response in the kidney and the subsequent effect on renal function have not been well characterized. This study investigated the impact of high and low thoracic (T) SCI on C-fos, TNFα, interleukin (IL)-1β, and IL-6 expression in the kidney at acute and sub-chronic timepoints. Adult C57BL/6 mice received a moderate contusion SCI or sham procedures at T4 or T10. Uninjured mice served as naïve controls. mRNA levels of the proinflammatory cytokines IL-1β, IL-6, TNFα, and C-fos, and TNFα and C-fos protein expression were assessed in the kidney and spinal cord 1 day and 14 days post-injury. The mRNA levels of all targets were robustly increased in the kidney and spinal cord, 1 day after both injuries. Whereas IL-6 and TNFα remained elevated in the spinal cord at 14 days after SCI, C-fos, IL-6, and TNFα levels were sustained in the kidney only after T10 SCI. TNFα protein was significantly upregulated in the kidney 1 day after both T4 and T10 SCI. Overall, these results clearly demonstrate that SCI induces robust systemic inflammation that extends to the kidney. Hence, the presence of renal inflammation can substantially impact renal pathophysiology and function after SCI.

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“…While cervical SCI clearly impair respiration due to direct injury to respiratory neural circuits that impact sleep [52][53][54] , there is little consideration on whether SCI -induced neural dysfunction in other areas may interact with an impact respiration. Nonetheless, recent work has shown that, when recorded in restraint cylinders, respiratory rate increases after thoracic contusion or hemisection injury that may precede to correspond with the emergence of allodynia 40,41 . In comparison, and recordings of respiratory rate in naturally behaving mice, we observed no change in average respiration rate but with increases respiratory rate variability (RRV).…”

Section: Respiration Changes After Scimentioning

confidence: 99%

“…Similarly, while there are several studies describing respiratory-related sleep dysfunction caused by cervical SCI 34,37,38 , including sleep apnea 39 , preclinical work aimed at understanding whether alterations in respiration associated with SCI -induced neuropathic pain are limited. Using lower thoracic SCI models that do not overtly impair respiratory neural circuits, studies in a restraint cylinder showed respiratory rate increases after thoracic contusion or hemisection injury that associate with the emergence of allodynia 40,41 . This important observation needs to be reproduced during natural behavior, which have relied on whole-body plethysmography 42 that has limited its applications in SCI animal models 43 .…”

Section: Introductionmentioning

confidence: 99%

Relating spinal injury-induced neuropathic pain and spontaneous afferent activity to sleep and respiratory dysfunction

Idlett-Ali

Kloefkorn

Goolsby³

et al. 2021

Preprint

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Spinal cord injury (SCI) can induce dysfunction in a multitude of neural circuits including those that lead to impaired sleep, respiratory dysfunction and neuropathic pain. We used a lower thoracic rodent contusion SCI model - known to develop mechanosensory stimulus hypersensitivity, and spontaneous activity in primary afferents that associates neuropathic pain - and paired this with new approaches that enabled chronic capture of three state sleep and respiration to characterize dysfunction and assess possible interrelations. Noncontact electric field sensors were embedded into home cages for noninvasive capture in naturally behaving mice of the temporal evolution of sleep and respiration changes for 6 weeks after SCI. Hindlimb mechanosensitivity was assessed weekly, and terminal experiments measured primary afferent spontaneous activity in situ from intact lumbar dorsal root ganglia (DRG). We observed that SCI led to increased spontaneous primary afferent activity (both firing rate and the number of spontaneously active DRGs) that correlated with reduced hindpaw mechanical sensitivity, increased respiratory rate variability, and increased sleep fragmentation. This is the first study to measure and link sleep dysfunction and variability in respiratory rate in a SCI model of neuropathic pain, and thereby provide broader insight into the magnitude of overall stress burden initiated by neural circuit dysfunction after SCI.

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Spontaneous and Stimulus-Evoked Respiratory Rate Elevation Corresponds to Development of Allodynia in Spinal Cord–Injured Rats

Cited by 7 publications

References 76 publications

Pharmacogenetic inhibition of TrkB signaling in adult mice attenuates mechanical hypersensitivity and improves locomotor function after spinal cord injury

Pharmacogenetic inhibition of TrkB signaling in adult mice attenuates mechanical hypersensitivity and improves locomotor function after spinal cord injury

Spinal Cord Injury Increases Pro-inflammatory Cytokine Expression in Kidney at Acute and Sub-chronic Stages

Relating spinal injury-induced neuropathic pain and spontaneous afferent activity to sleep and respiratory dysfunction

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