Individuals With Prior Chronic Pain and Long-Term Opioid Treatment May Experience Persistence of That Pain Even After Subsequent Complete Cervical Spinal Cord Injury: Suggestions From a Prospective Case-Controlled Study
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SUBMITTER: Hecht J
PROVIDER: S-EPMC11240028 | biostudies-literature | 2024 Apr
REPOSITORIES: biostudies-literature
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Project description:Approximately one-third of people with a spinal cord injury (SCI) will experience persistent neuropathic pain following injury. This pain negatively affects quality of life and is difficult to treat. Opioids are among the most effective drug treatments, and are commonly prescribed, but experimental evidence suggests that opioid treatment in the acute phase of injury can attenuate recovery of locomotor function. In fact, spinal cord injury and opioid administration share several common features (e.g. central sensitization, excitotoxicity, aberrant glial activation) that have been linked to impaired recovery of function, as well as the development of pain. Despite these effects, the interactions between opioid use and spinal cord injury have not been fully explored. A review of the literature, described here, suggests that caution is warranted when administering opioids after SCI. Opioid administration may synergistically contribute to the pathology of SCI to increase the development of pain, decrease locomotor recovery, and leave individuals at risk for infection. Considering these negative implications, it is important that guidelines are established for the use of opioids following spinal cord and other central nervous system injuries.
| S-EPMC3742731 | biostudies-literature
Project description:Release of endogenous dynorphin opioids within the spinal cord after partial sciatic nerve ligation (pSNL) is known to contribute to the neuropathic pain processes. Using a phosphoselective antibody [kappa opioid receptor (KOR-P)] able to detect the serine 369 phosphorylated form of the KOR, we determined possible sites of dynorphin action within the spinal cord after pSNL. KOR-P immunoreactivity (IR) was markedly increased in the L4-L5 spinal dorsal horn of wild-type C57BL/6 mice (7-21 d) after lesion, but not in mice pretreated with the KOR antagonist nor-binaltorphimine (norBNI). In addition, knock-out mice lacking prodynorphin, KOR, or G-protein receptor kinase 3 (GRK3) did not show significant increases in KOR-P IR after pSNL. KOR-P IR was colocalized in both GABAergic neurons and GFAP-positive astrocytes in both ipsilateral and contralateral spinal dorsal horn. Consistent with sustained opioid release, KOR knock-out mice developed significantly increased tactile allodynia and thermal hyperalgesia in both the early (first week) and late (third week) interval after lesion. Similarly, mice pretreated with norBNI showed enhanced hyperalgesia and allodynia during the 3 weeks after pSNL. Because sustained activation of opioid receptors might induce tolerance, we measured the antinociceptive effect of the kappa agonist U50,488 using radiant heat applied to the ipsilateral hindpaw, and we found that agonist potency was significantly decreased 7 d after pSNL. In contrast, neither prodynorphin nor GRK3 knock-out mice showed U50,488 tolerance after pSNL. These findings suggest that pSNL induced a sustained release of endogenous prodynorphin-derived opioid peptides that activated an anti-nociceptive KOR system in mouse spinal cord. Thus, endogenous dynorphin had both pronociceptive and antinociceptive actions after nerve injury and induced GRK3-mediated opioid tolerance.
| S-EPMC2376823 | biostudies-literature
Project description:The management of visceral pain is a major clinical problem in patients affected by gastrointestinal disorders. The poor knowledge about pain chronicization mechanisms prompted us to study the functional and morphological alterations of the gut and nervous system in the animal model of persistent visceral pain caused by 2,4-dinitrobenzenesulfonic acid (DNBS). This agent, injected intrarectally, induced a colonic inflammation peaking on day 3 and remitting progressively from day 7. In concomitance with bowel inflammation, the animals developed visceral hypersensitivity, which persisted after colitis remission for up to three months. On day 14, the administration of pain-relieving drugs (injected intraperitoneally and intrathecally) revealed a mixed nociceptive, inflammatory and neuropathic pain originating from both the peripheral and central nervous system. At this time point, the colonic histological analysis highlighted a partial restitution of the tunica mucosa, transmural collagen deposition, infiltration of mast cells and eosinophils, and upregulation of substance P (SP)-positive nerve fibers, which were surrounded by eosinophils and MHC-II-positive macrophages. A significant activation of microglia and astrocytes was observed in the dorsal and ventral horns of spinal cord. These results suggest that the persistence of visceral pain induced by colitis results from maladaptive plasticity of the enteric, peripheral and central nervous systems.
| S-EPMC7464824 | biostudies-literature
Project description:Because the presence of pain impedes motor recovery in individuals with spinal cord injury (SCI), it is necessary to understand their supraspinal substrates in translational animal models. Using functional magnetic resonance imaging (fMRI) in a rat model of hemicontusion cervical SCI, supraspinal changes were mapped and correlated with sensorimotor behavioral outcomes. Female adult rats underwent sham or SCI using a 2.5 mm impactor and 150 kdyn force. SCI permanently impaired motor activity in only the ipsilesional forelimb along with thermal hyperalgesia at 5 and 6 weeks. Spinal MRI at 8 weeks after SCI showed ipsilateral T1 and T2 lesions with no discernable lesions across shams. fMRI mapping during electrical forepaw stimulation indicated SCI-induced sensorimotor reorganization with an expansion of the contralesional forelimb representation. Resting state fMRI-based functional connectivity density (FCD), a marker of regional neuronal hubs, increased or decreased across brain regions involved in nociception. FCD increases after SCI were in the primary and secondary somatosensory cortices (S1 and S2), anterior cingulate cortex (ACC), insula, and the pre-frontal cortex (PFC), and decreases were across the hippocampus, thalamus, hypothalamus, and amygdala in SCI. Resting state functional connectivity (RSFC) assessments from the FCD altered regions of interest indicated cortico-cortical RSFC increases and cortico-insular, cortico-thalamic, and cortico-hypothalamic RSFC decreases after SCI. Hippocampus, amygdala, and thalamus showed decreased RSFC with most cortical regions and between themselves except the hippocampus-amygdala network, which showed increased RSFC after SCI. Whereas select nociceptive region's intrinsic activity associated strongly with evoked pain behaviors after SCI (e.g., PFC, ACC, hippocampus, thalamus, hypothalamus, M1, and S1BF) other nociceptive regions had weaker associations (e.g., amygdala, insula, auditory cortex, S1FL, S1HL, S2, and M2), but differed significantly in their intrinsic activities between sham and SCI. The weaker associated nociceptive regions may possibly encode both the evoked and affective components of pain.
| S-EPMC8713267 | biostudies-literature
Project description:IntroductionDegenerative Cervical Myelopathy [DCM] is a slow-motion spinal cord injury. Compression and dynamic compression have been considered disease hallmarks. However, this is likely an oversimplification, as compression is more commonly incidental and has only modest correlation to disease severity. MRI studies have recently suggested spinal cord oscillation could play a role.Research questionTo determine if spinal cord oscillation could contribute to spinal cord injury in degenerative cervical myelopathy.Material and methodsA computational model of an oscillating spinal cord was developed from imaging of a healthy volunteer. Using finite element analysis, the observed implications of stress and strain, were measured in the context of a simulated disc herniation. The significance was bench marked by comparison to a more recognised dynamic injury mechanism; a flexion extension model of dynamic compression.ResultsSpinal cord oscillation altered both compressive and shear strain on the spinal cord. Following initial compression, compressive strain moves from within the spinal cord to the spinal cord surface, whilst shear strain is magnified by 0.1-0.2, depending on the amplitude of oscillation. These orders of magnitude are equivalent to a dynamic compression model.Discussion and conclusionSpinal cord oscillation could significantly contribute to spinal cord damage across DCM. Its repeated occurrence with every heartbeat, draws parallels to the concept of fatigue damage, which could reconcile differing theories on the origins of DCM. This remains hypothetical at this stage, and further investigations are required.
| S-EPMC10293319 | biostudies-literature
Project description:BackgroundDegenerative cervical spinal cord compression is becoming increasingly prevalent, yet the MRI criteria that define compression are vague, and vary between studies. This contribution addresses the detection of compression by means of the Spinal Cord Toolbox (SCT) and assesses the variability of the morphometric parameters extracted with it.MethodsProspective cross-sectional study. Two types of MRI examination, 3 and 1.5 T, were performed on 66 healthy controls and 118 participants with cervical spinal cord compression. Morphometric parameters from 3T MRI obtained by Spinal Cord Toolbox (cross-sectional area, solidity, compressive ratio, torsion) were combined in multivariate logistic regression models with the outcome (binary dependent variable) being the presence of compression determined by two radiologists. Inter-trial (between 3 and 1.5 T) and inter-rater (three expert raters and SCT) variability of morphometric parameters were assessed in a subset of 35 controls and 30 participants with compression.ResultsThe logistic model combining compressive ratio, cross-sectional area, solidity, torsion and one binary indicator, whether or not the compression was set at level C6/7, demonstrated outstanding compression detection (area under curve =0.947). The single best cut-off for predicted probability calculated using a multiple regression equation was 0.451, with a sensitivity of 87.3% and a specificity of 90.2%. The inter-trial variability was better in Spinal Cord Toolbox (intraclass correlation coefficient was 0.858 for compressive ratio and 0.735 for cross-sectional area) compared to expert raters (mean coefficient for three expert raters was 0.722 for compressive ratio and 0.486 for cross-sectional area). The analysis of inter-rater variability demonstrated general agreement between SCT and three expert raters, as the correlations between SCT and raters were generally similar to those of the raters between one another.ConclusionsThis study demonstrates successful semi-automated compression detection based on four parameters. The inter-trial variability of parameters established through two MRI examinations was conclusively better for Spinal Cord Toolbox compared with that of three experts' manual ratings.
| S-EPMC8923862 | biostudies-literature
Project description:The number of elderly patients with spinal cord injury without radiographic abnormalities (SCIWORA) has been increasing in recent years and common of most cervical spinal cord injuries. Basic research has shown the effectiveness of early decompression after spinal cord injury on the spinal cord without stenosis; no studies have reported the efficacy of decompression in models with spinal cord compressive lesions. The purpose of this study was to evaluate the effects of decompression surgery after acute spinal cord injury in rats with chronic spinal cord compressive lesions, mimicking SCIWORA. A water-absorbent polymer sheet (Aquaprene DX, Sanyo Chemical Industries) was inserted dorsally into the 4-5th cervical sublaminar space in 8-week-old Sprague Dawley rats to create a rat model with a chronic spinal compressive lesion. At the age of 16 weeks, 30 mildly myelopathic or asymptomatic rats with a Basso, Beattie, and Bresnahan score (BBB score) of 19 or higher were subjected to spinal cord compression injuries. The rats were divided into three groups: an immediate decompression group (decompress immediately after injury), a sub-acute decompression group (decompress 1 week after injury), and a non-decompression group. Behavioral and histological evaluations were performed 4 weeks after the injury. At 20 weeks of age, the BBB score and FLS (Forelimb Locomotor Scale) of both the immediate and the sub-acute decompression groups were significantly higher than those of the non-decompression group. There was no significant difference between the immediate decompression group and the sub-acute decompression group. TUNEL (transferase-mediated dUTP nick end labeling) staining showed significantly fewer positive cells in both decompression groups compared to the non-decompression group. LFB (Luxol fast blue) staining showed significantly more demyelination, and GAP-43 (growth associated protein-43) staining tended to show fewer positive cells in the non-decompression group. Decompression surgery in the acute or sub-acute phase of injury is effective after mild spinal cord injury in rats with chronic compressive lesions. There was no significant difference between the immediate decompression and sub-acute decompression groups.
| S-EPMC9402533 | biostudies-literature
Project description:The study aimed to determine whether asymptomatic rats with cervical spinal cord compression (CSCC) experience more severe cervical spinal cord injury (SCI) compared with rats without CSCC under the same degree of minor trauma. Four weeks after the polyvinyl alcohol-polyacrylamide hydrogel was implanted into the C5 vertebral canal, asymptomatic rats were selected based on locomotor function score. Mild cervical SCI was subsequently established based on CSCC. The motor function, morphology, neuron loss, myelin destruction, nerve cell apoptosis, microglia activation, and neuroinflammation were evaluated after SCI. Under the same injury conditions, rats in the CSCC group exhibited more severe motor dysfunction compared with those without CSCC. Similarly, asymptomatic CSCC rats showed significant damage to spinal cord tissue, neurons, and myelin. Finally, compared with rats without CSCC, asymptomatic CSCC rats experienced increased nerve cell apoptosis, microglial activation, and neuroinflammation following the same SCI. In asymptomatic CSCC rats, the same degree of minor trauma resulted in more severe cervical SCI compared with rats without CSCC. This was evidenced by increased nerve cell apoptosis, microglial activation, neuron death, myelin destruction, and a strong neuroinflammatory response, leading to severe motor dysfunction.
| S-EPMC11661568 | biostudies-literature
Project description:Cervical spinal cord injury (SCI) leads to impaired trunk motor control, negatively impacting the performance of activities of daily living in the affected individuals. Improved trunk control with better sitting posture has been previously observed due to neuromuscular electrical stimulation and transcutaneous spinal stimulation, while improved postural stability has been observed with spinal cord epidural stimulation (scES). Hence, we studied how trunk-specific scES impacts sitting independence and posture. Fourteen individuals with chronic, severe cervical SCI with an implanted neurostimulator performed a 5-min tall-sit task without and with trunk-specific scES. Spine posture was assessed by placing markers on five spine levels and evaluating vertical spine inclination angles. Duration of trunk manual assistance was used to assess independence along with the number of independence changes and average independence score across those changes. With scES, the sacrum-L1 inclination and number of independence changes tended to decrease by 1.64 ± 3.16° (p = 0.07; Cohen's d = 0.53) and 9.86 ± 16.8 (p = 0.047; Cohen's d = 0.59), respectively. Additionally, for the participants who had poor sitting independence without scES, level of independence tended to increase by 12.91% [0%, 31.52%] (p = 0.38; Cohen's d = 0.96) when scES was present. Hence, trunk-specific scES promoted improvements in lower spine posture and lower levels of trunk assistance.
| S-EPMC10525621 | biostudies-literature
Project description:IntroductionNeuropathic pain is a common complication of spinal cord injury (SCI), and is notoriously difficult to adequately treat. Gunshot wounds (GSW) near the spinal cord may cause intractable chronic pain through spinal/nerve root transection, or reactive tissue formation resulting in nerve root compression from retained bullet fragments (RBF).Case presentationThis case report describes a 30-year-old man with a T12 AIS B incomplete spinal cord injury with paraplegia secondary to multiple GSW who presented with severe bilateral lower extremity dysesthesias and muscle spasms. Symptoms failed to improve with oral antispasmodic medications. After being diagnosed with Complex regional pain syndrome (CRPS) type I secondary to an SCI via GSW, he underwent a spinal cord stimulator (SCS) trial, which improved his symptoms by greater than 80%.DiscussionNeuropathic pain refractory to conservative treatment may benefit from SCS. Effects of therapy go beyond gate-theory in SCI patients, and may benefit patients at the cellular and molecular level. Our case demonstrates the effectiveness of SCS treatment in a patient who developed CRPS type 1 after GSW resulting in SCI.
| S-EPMC9478097 | biostudies-literature