Decreased Spinothalamic and Dorsal Column Medial Lemniscus-Mediated Function Is Associated with Neuropathic Pain after Spinal Cord Injury

Cruz-Almeida, Yenisel; Felix, Elizabeth R.; Martinez‐Arizala, Alberto; Widerström-Noga, Eva

doi:10.1089/neu.2012.2343

Cited by 45 publications

(34 citation statements)

References 48 publications

(81 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results also concur with previous studies where severity of neuropathic pain symptoms in persons with SCI was associated with greater sensitivity to thermal nonpainful and painful stimuli below the level of injury. 12,17 …”

Section: Discussionmentioning

confidence: 99%

“…The CPT and HPT were similarly measured using 3 trials, a stimulus interval of at least 30 seconds, and a temperature change of 1.5°C per second. Greater detail regarding all performed QST procedures can be found in the studies of Felix and Widerström-Noga 17 and Cruz-Almeida et al 12 …”

Section: Methodsmentioning

confidence: 99%

“…3 Results from human QST studies have consistently suggested that injury involving the spinothalamic tract (STT) is related to the presence and/or severity of neuropathic pain after SCI. 12,17,19,20,78 Human SCI research also shows that greater residual STT function is significantly related to more intense neuropathic pain. 12,17,78 To the best of our knowledge, no previous study has examined to what extent somatosensory function is associated with thalamic Glx/Ins in persons with neuropathic SCI-related pain.…”

Section: Introductionmentioning

confidence: 99%

“…12,17,19,20,78 Human SCI research also shows that greater residual STT function is significantly related to more intense neuropathic pain. 12,17,78 To the best of our knowledge, no previous study has examined to what extent somatosensory function is associated with thalamic Glx/Ins in persons with neuropathic SCI-related pain. Because the thalamus is a brain area critical to the processing, integration, and modulation of sensory nociceptive information, 58,91 we hypothesized that lower thalamic Glx/Ins ratios (suggesting decreased glutamatergic metabolism in combination with glial proliferation or activation) and more intense neuropathic pain would be associated with a sensory phenotype with more residual STT function.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Somatosensory phenotype is associated with thalamic metabolites and pain intensity after spinal cord injury

Widerström-Noga

Cruz-Almeida

Felix

et al. 2015

Pain

Self Cite

View full text Add to dashboard Cite

Neuropathic pain is one of the most difficult consequences of spinal cord injury (SCI). The clinical correlates of the underlying mechanisms responsible for neuropathic pain are not well understood, although methods such as quantitative somatosensory testing (QST) or brain imaging have been used to further a mechanism-based understanding of pain. Our previous SCI study demonstrated a significantly lower glutamate-glutamine/myo-inositol ratio (Glx/Ins) in the anterior cingulate cortex in persons with severe neuropathic pain compared with those with less severe neuropathic pain or pain-free, able-bodied controls, suggesting that a combination of decreased glutamatergic metabolism and glial activation may contribute to the development of severe neuropathic pain after SCI. The present study aimed to determine the relationships between somatosensory function below the level of injury and low thalamic Glx/Ins in persons with intense neuropathic pain after SCI. Participants underwent QST and a 3 Tesla proton magnetic resonance spectroscopy. A cluster analysis including SCI participants resulted in 1 group (n = 19) with significantly (P < 0.001) greater pain intensity (6.43 ± 1.63; high neuropathic pain [HNP], and lower Glx/Ins [1.22 ± 0.16]) and another group (n = 35) with lower pain intensity ratings (1.59 ± 1.52, low neuropathic pain [LNP], and higher Glx/Ins [1.47 ± 0.26]). After correcting for age, QST indicated significantly greater somatosensory function in the HNP group compared with the LNP group. Our results are consistent with research suggesting that damage to, but not abolition of, the spinothalamic tract contributes to development of neuropathic pain after SCI and that secondary inflammatory processes may amplify residual spinothalamic tract signals by facilitation, disinhibition, or sensitization.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Somatosensory phenotype is associated with thalamic metabolites and pain intensity after spinal cord injury

Widerström-Noga

Cruz-Almeida

Felix

et al. 2015

Pain

Self Cite

View full text Add to dashboard Cite

show abstract

“…Without input to 3b/1 via the DC–ML path, the inhibition of area 3a that normally results from activation of 3b/1 neurons by myelinated afferent input is reduced/eliminated, leading to an enhanced response of area 3a neurons to activity arising from unmyelinated nociceptors. Similarly, human patients with large spinal lesions that include the DCs report substantially increased sensitivity/responsivity to noxious stimulation [82], and chronic pain from spinal cord injury is more prevalent among patients with substantial damage the DC-ML pathway [34]. …”

Section: Spinal Thalamic and Cortical Lesions Affecting Pain Procmentioning

confidence: 99%

Role of primary somatosensory cortex in the coding of pain

Vierck

Whitsel

Favorov

et al. 2013

Pain

212

157

View full text Add to dashboard Cite

The intensity and submodality of pain are widely attributed to stimulus encoding by peripheral and subcortical spinal/trigeminal portions of the somatosensory nervous system. Consistent with this interpretation are studies of surgically anesthetized animals, showing that relationships between nociceptive stimulation and activation of neurons are similar at subcortical levels of somatosensory projection and within the primary somatosensory cortex (in cytoarchitectural areas 3b and 1 of SI). Such findings have led to characterizations of SI as a network which preserves, rather than transforms, the excitatory drive it receives from subcortical levels. Inconsistent with this perspective are images and neurophysiological recordings of SI neurons in lightly anesthetized primates. These studies show that an extreme anterior position within SI (area 3a) receives input originating predominantly from unmyelinated nociceptors, distinguishing it from posterior SI (areas 3b and 1), long recognized as receiving input predominantly from myelinated afferents, including nociceptors. Of particular importance, interactions between these subregions during maintained nociceptive stimulation are accompanied by an altered SI response to myelinated and unmyelinated nociceptors. A revised view of pain coding within SI cortex is discussed, and potentially significant clinical implications are emphasized.

show abstract

Assessment of Somatosensory Function in Patients With Idiopathic Dry Eye Symptoms

Galor

Levitt

McManus³

et al. 2016

JAMA Ophthalmol

Self Cite

View full text Add to dashboard Cite

IMPORTANCE Somatosensory dysfunction likely underlies dry eye (DE) symptoms in many individuals yet remains an understudied component of the disease. Its presence has important diagnostic and therapeutic implications. OBJECTIVE To assess the integrity of nociceptive system processes in persons with DE and ocular pain using quantitative sensory testing (QST) techniques applied at a site remote from the eye. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional study conducted at Miami Veterans Affairs Hospital included 118 individuals with a wide variety of DE symptoms and signs. The study was conducted from October 31, 2013, to January 28, 2016. INTERVENTIONS Individuals completed questionnaires regarding ocular symptoms (5-Item Dry Eye Questionnaire [DEQ5], Ocular Surface Disease Index [OSDI], and Neuropathic Pain Symptom Inventory modified for the eye [NPSI-E]), psychological status, and medication use and underwent an ocular surface examination. The QST metrics included measures of vibratory and thermal thresholds and cold and hot pain temporal summation (surrogate measures of central sensitization) on the forearm. MAIN OUTCOMES AND MEASURES Correlations among DE and ocular pain symptom severity with QST metrics measured on the forearm. The OSDI score ranges from 0 to 100, with 100 indicating the most severe DE symptoms. The DEQ5 score ranges from 0 to 22, with the highest score indicating the most severe symptoms, and the NPSI-E score ranges from 0 to 100, with the highest score indicating the most severe symptoms. Psychological state was measured with the 9-item Patient Health Questionnaire, the PTSD Checklist-Military Version for PTSD, and the Symptom Checklist-90 for anxiety. RESULTS Of the 118 patients who participated in the study, 105 (88.9%) were men (mean [SD] age, 60 [10] years), and a mean of 41% had PTSD, 10% depression, and 0.93% anxiety. Using stepwise linear regression analyses, significant associations were identified between overall DE symptom severity and posttraumatic stress disorder scores and tear breakup time (DEQ5 model: R = 0.54; OSDI model: R = 0.61, P < .001). All other variables (ie, demographics, comorbidities, medications, tear film factors, and QST metrics) dropped out of these models. When specifically considering neuropathic-like qualities of DE pain, however, anxiety and hot pain temporal summation at the forearm explained 17% of the variability in ocular burning (R = 0.41; P < .001), and PTSD score, tear breakup time, and hot pain temporal summation at the forearm explained 25% of the variability in sensitivity to wind (R = 0.50; P < .001) and 30% of the variability in total NPSI-E scores (R = 0.55; P < .001). CONCLUSIONS AND RELEVANCE Our findings demonstrate that neuropathic-like DE pain symptom severity correlates with quantitative measures of pain sensitivity at a site remote from the eye. This result provides additional evidence that DE symptoms are not only manifestations of a local disorder but also involve somatosensory dysfunction beyond the trigeminal system.

show abstract

Decreased Spinothalamic and Dorsal Column Medial Lemniscus-Mediated Function Is Associated with Neuropathic Pain after Spinal Cord Injury

Cited by 45 publications

References 48 publications

Somatosensory phenotype is associated with thalamic metabolites and pain intensity after spinal cord injury

Somatosensory phenotype is associated with thalamic metabolites and pain intensity after spinal cord injury

Role of primary somatosensory cortex in the coding of pain

Assessment of Somatosensory Function in Patients With Idiopathic Dry Eye Symptoms

Contact Info

Product

Resources

About