Pharmacological Transection of Brain–Spinal Cord Communication Blocks Pain-Induced Hemorrhage and Locomotor Deficits after Spinal Cord Injury in Rats

Davis, Jacob A.; Bopp, Anne C.; Henwood, Melissa K.; Baine, Rachel E; Cox, Carol C; Grau, James W.

doi:10.1089/neu.2019.6973

Cited by 9 publications

(8 citation statements)

References 34 publications

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“…Engaging nociceptive fibers with electrical stimulation or capsaicin a day after injury induced a lasting impairment in locomotor function, comparable in overall magnitude to that observed in male rats. 6 , 11 , 44 Unlike male rats, there was no effect of nociceptive stimulation on body weight during the recovery period; independent of treatment, female rats stayed at approximately the same weight. In contrast, young adult (80–120 days of age) male rats typically gain weight, and this effect is stilted by exposure to noxious stimulation after injury.…”

Section: Discussionmentioning

confidence: 90%

“… 40 , 50 Similar results were obtained when a pharmacological transection was performed by slowly infusing the anesthetic, lidocaine, onto the spinal cord tissue at T2. 44 On the basis of these findings, we have suggested that the adverse effect of nociceptive input after injury depends, in part, on brain systems. Interestingly, these brain-dependent effects do not appear to depend upon psychological pain/affect, because an analgesic dose of morphine does not block hemorrhage or the adverse effect nociceptive stimulation has on recovery.…”

Section: Discussionmentioning

confidence: 99%

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Noxious Stimulation Induces Acute Hemorrhage and Impairs Long-Term Recovery after Spinal Cord Injury (SCI) in Female Rats: Evidence Estrous Cycle May Have a Modulatory Effect

Baine

Johnston

Strain³

et al. 2022

Neurotrauma Reports

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Spinal cord injuries (SCIs) are often the result of traumatic accidents, which also produce multiple other injuries (polytrauma). Nociceptive input from associated injuries has been shown to significantly impair recovery post-SCI. Historically, work in our laboratory has focused exclusively on male animals; however, increasing incidence of SCI in females requires research to determine whether pain (nociceptive) input poses the same risk to their recovery. Some animal studies have shown that females demonstrate greater tissue preservation and better locomotor recovery post-SCI. Given this, we examined the effect of sex on SCI recovery in two pain models—intermittent electrical stimulation (shock) to the tail or capsaicin injection to the hindpaw. Female rats received a lower thoracic contusion injury and were exposed to noxious stimulation the next day. The acute effect of noxious input on cardiovascular function, locomotor performance, and hemorrhage were assessed. Treatment with capsaicin or noxious electrical stimulation disrupted locomotor performance, increased blood pressure, and disrupted stepping. Additional experiments examined the long-term consequences of noxious input, demonstrating that both noxious electrical stimulation and capsaicin impair long-term recovery in female rats. Interestingly, injury had a greater effect on behavioral performance when progesterone and estrogen were low (metestrus). Conversely, nociceptive input led to a greater disruption in locomotor performance and produced a greater rise in blood pressure in animals injured during estrus.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Noxious Stimulation Induces Acute Hemorrhage and Impairs Long-Term Recovery after Spinal Cord Injury (SCI) in Female Rats: Evidence Estrous Cycle May Have a Modulatory Effect

Baine

Johnston

Strain³

et al. 2022

Neurotrauma Reports

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“…In prior studies, we have shown that the intrathecal lidocaine procedure used here inhibits spinally mediated learning (Crown et al, 2002a), the induction of maladaptive plasticity (Joynes et al, 2003), and brain-dependent responses to nociceptive stimulation in contused rats (Davis et al, 2020). To further verify the effectiveness of this treatment, we tested its effect on the performance of a spinally mediated reflex [tail withdrawal from a noxious thermal stimulus (tail-flick test)].…”

Section: Resultsmentioning

confidence: 99%

Evidence That the Central Nervous System Can Induce a Modification at the Neuromuscular Junction That Contributes to the Maintenance of a Behavioral Response

et al. 2020

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Neurons within the spinal cord are sensitive to environmental relations and can bring about a behavioral modification without input from the brain. For example, rats that have undergone a thoracic (T2) transection can learn to maintain a hind leg in a flexed position to minimize exposure to a noxious electrical stimulation (shock). Inactivating neurons within the spinal cord with lidocaine, or cutting communication between the spinal cord and the periphery (sciatic transection), eliminates the capacity to learn, which implies that it depends on spinal neurons. Here we show that these manipulations have no effect on the maintenance of the learned response, which implicates a peripheral process. EMG showed that learning augments the muscular response evoked by motoneuron output and that this effect survives a sciatic transection. Quantitative fluorescent imaging revealed that training brings about an increase in the area and intensity of ACh receptor labeling at the neuromuscular junction (NMJ). It is hypothesized that efferent motoneuron output, in conjunction with electrical stimulation of the tibialis anterior muscle, strengthens the connection at the NMJ in a Hebbian manner. Supporting this, paired stimulation of the efferent nerve and tibialis anterior generated an increase in flexion duration and augmented the evoked electrical response without input from the spinal cord. Evidence is presented that glutamatergic signaling contributes to plasticity at the NMJ. Labeling for vesicular glutamate transporter is evident at the motor endplate. Intramuscular application of an NMDAR antagonist blocked the acquisition/maintenance of the learned response and the strengthening of the evoked electrical response.

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“…Given these observations, we naturally hypothesized that noxious stimulation would lead to greater tissue loss and hemorrhage after a contusion injury if communication with the brain was cut. We found exactly the opposite—that disrupting communication with the brain by means of a surgical or pharmacological transection at T2 blocks nociception-induced hemorrhage in rats that had a lower thoracic contusion injury [ 423 , 424 ]. A T2 transection also blocked the activation of pro-inflammatory cytokines, and signals indicative of cell death, at the site of injury.…”

Section: Discussionmentioning

confidence: 99%

Role of Descending Serotonergic Fibers in the Development of Pathophysiology after Spinal Cord Injury (SCI): Contribution to Chronic Pain, Spasticity, and Autonomic Dysreflexia

Fauss

Hudson

Grau

2022

Biology

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As the nervous system develops, nerve fibers from the brain form descending tracts that regulate the execution of motor behavior within the spinal cord, incoming sensory signals, and capacity to change (plasticity). How these fibers affect function depends upon the transmitter released, the receptor system engaged, and the pattern of neural innervation. The current review focuses upon the neurotransmitter serotonin (5-HT) and its capacity to dampen (inhibit) neural excitation. A brief review of key anatomical details, receptor types, and pharmacology is provided. The paper then considers how damage to descending serotonergic fibers contributes to pathophysiology after spinal cord injury (SCI). The loss of serotonergic fibers removes an inhibitory brake that enables plasticity and neural excitation. In this state, noxious stimulation can induce a form of over-excitation that sensitizes pain (nociceptive) circuits, a modification that can contribute to the development of chronic pain. Over time, the loss of serotonergic fibers allows prolonged motor drive (spasticity) to develop and removes a regulatory brake on autonomic function, which enables bouts of unregulated sympathetic activity (autonomic dysreflexia). Recent research has shown that the loss of descending serotonergic activity is accompanied by a shift in how the neurotransmitter GABA affects neural activity, reducing its inhibitory effect. Treatments that target the loss of inhibition could have therapeutic benefit.

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Pharmacological Transection of Brain–Spinal Cord Communication Blocks Pain-Induced Hemorrhage and Locomotor Deficits after Spinal Cord Injury in Rats

Cited by 9 publications

References 34 publications

Noxious Stimulation Induces Acute Hemorrhage and Impairs Long-Term Recovery after Spinal Cord Injury (SCI) in Female Rats: Evidence Estrous Cycle May Have a Modulatory Effect

Noxious Stimulation Induces Acute Hemorrhage and Impairs Long-Term Recovery after Spinal Cord Injury (SCI) in Female Rats: Evidence Estrous Cycle May Have a Modulatory Effect

Evidence That the Central Nervous System Can Induce a Modification at the Neuromuscular Junction That Contributes to the Maintenance of a Behavioral Response

Role of Descending Serotonergic Fibers in the Development of Pathophysiology after Spinal Cord Injury (SCI): Contribution to Chronic Pain, Spasticity, and Autonomic Dysreflexia

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