Changes in spinal reflex and locomotor activity after a complete spinal cord injury: a common mechanism?

Locomotor activity and spinal reflexes (SRs) show common features in different mammals, including humans. Here we report the time-course of the development of locomotor activity and SRs after a complete spinal cord injury in humans. SRs evoked by tibial nerve stimulation were studied, as was the leg muscle electromyography activity evoked by mechanically assisted locomotion (Lokomat) in biceps femoris, rectus femoris, tibialis anterior and gastrocenmius medialis. Around 8 weeks after the injury, an early SR component (latency 60-120 ms) appeared, as in healthy subjects, and a well-organized leg muscle activity was present during assisted locomotion. At around 6 months after injury an additional, late reflex component (latency 120-450 ms) appeared, which remained even 15 years after the spinal cord injury. In contrast, the early component had markedly decreased at 18 months after injury. These changes in SR were associated with a loss of electromyography activity and a successively stronger electromyography exhaustion (i.e. decline of electromyography amplitude), when comparing the level of electromyography activity at 2 and 10 min, respectively, during assisted locomotion. These changes in electromyography activity affected mainly the biceps femoris, gastrocenmius medialis and tibialis anterior but less so the rectus femoris. When the amplitude relationship of the early to late SR component was calculated, there was a temporal relationship between the decrease of the early component and an increase of the late component and the degree of exhaustion of locomotor activity. In chronic, severely affected but sensori-motor incomplete spinal cord injury subjects a late SR component, associated with an electromyography exhaustion, was present in subjects who did not regularly perform stepping movements. Our data are consistent with the proposal of a common mechanism underlying the changes in SR activity and locomotor activity after spinal cord injury. These findings should be taken into consideration in the development of novel rehabilitation schemes and programs to facilitate regeneration-inducing therapies in spinal cord injury subject

Are changes in nociceptive withdrawal reflex magnitude a viable central sensitization proxy? Implications of a replication attempt

Objective: The nociceptive withdrawal reflex (NWR) has been proposed to read-out central sensitization (CS). Replicating a published study, it was assessed if the NWR magnitude reflects sensitization by painful heat. Additionally, NWR response rates were compared for two stimulation, the sural nerve at the lateral malleolus (SU) and the medial plantar nerve on the foot sole (MP), and three recording sites, biceps femoris (BF), rectus femoris (RF), and tibialis anterior (TA) muscles. Methods: 16 subjects underwent one experiment with six blocks of eight transcutaneous electrical stimulations to elicit the NWR while surface electromyography was collected. Tonic heat was concurrently applied in the same dermatome. Temperatures rose from 32 °C in the first to 46 °C in the last block following the previously published protocol. Results: Tonic heat did not influence NWR magnitude. The highest NWR response rate was obtained for MP-TA combination (79%). Regarding elicitation in all three muscles, SU stimulation outperformed MP (59% vs 57%). Conclusions: The replication failed. NWR magnitude as a CS proxy in healthy subjects needs continued investigation. With respect to response rates, MP-TA proved efficient, whereas SU stimulation seemed preferable for multiple muscle recordings. Significance: Unclear methodological descriptions in the original study affected CS and NWR replication. The NWR magnitude changes induced by CS may closely depend on the different stimulation methods used. Keywords: Central sensitization; Nociceptive withdrawal reflex; Reliability; Response rat

Novel neurophysiological evidence for preserved pain habituation across chronic pain conditions.

OBJECTIVE The present study aimed to investigate whether subjective and objective measures of pain habituation can be used as potential markers for central sensitization across various chronic pain patients. METHODS Two blocks of contact-heat stimuli were applied to a non-painful area in 93 chronic pain patients (low back pain, neuropathic pain, and complex regional pain syndrome) and 60 healthy controls (HC). Habituation of pain ratings, contact-heat evoked potentials (CHEP), and sympathetic skin responses (SSR) was measured. RESULTS There was no significant difference in any measure of pain habituation between patients and HC. Even patients with apparent clinical signs of central sensitization showed no reduced pain habituation. However, prolonged baseline CHEP and SSR latencies (stimulation block 1) were found in patients compared to HC (CHEP: Δ-latency = 23 ms, p = 0.012; SSR: Δ-latency = 100 ms, p = 0.022). CONCLUSION Given the performed multimodal neurophysiological testing protocol, we provide evidence indicating that pain habituation may be preserved in patients with chronic pain and thereby be of limited use as a sensitive marker for central sensitization. These results are discussed within the framework of the complex interactions between pro- and antinociceptive mechanism as well as methodological issues. The prolonged latencies of CHEP and SSR after stimulation in non-painful areas may indicate subclinical changes in the integrity of thermo-nociceptive afferents, or a shift towards antinociceptive activity. This shift could potentially affect the relay of ascending signals. SIGNIFICANCE Our findings challenge the prevailing views in the literature and may encourage further investigations into the peripheral and central components of pain habituation, using advanced multimodal neurophysiological techniques

Sensory phenotypes in complex regional pain syndrome and chronic low back pain-indication of common underlying pathomechanisms

INTRODUCTION First-line pain treatment is unsatisfactory in more than 50% of chronic pain patients, likely because of the heterogeneity of mechanisms underlying pain chronification. OBJECTIVES This cross-sectional study aimed to better understand pathomechanisms across different chronic pain cohorts, regardless of their diagnoses, by identifying distinct sensory phenotypes through a cluster analysis. METHODS We recruited 81 chronic pain patients and 63 age-matched and sex-matched healthy controls (HC). Two distinct chronic pain cohorts were recruited, ie, complex regional pain syndrome (N = 20) and low back pain (N = 61). Quantitative sensory testing (QST) was performed in the most painful body area to investigate somatosensory changes related to clinical pain. Furthermore, QST was conducted in a pain-free area to identify remote sensory alterations, indicating more widespread changes in somatosensory processing. RESULTS Two clusters were identified based on the QST measures in the painful area, which did not represent the 2 distinct pain diagnoses but contained patients from both cohorts. Cluster 1 showed increased pain sensitivities in the painful and control area, indicating central sensitization as a potential pathomechanism. Cluster 2 showed a similar sensory profile as HC in both tested areas. Hence, either QST was not sensitive enough and more objective measures are needed to detect sensitization within the nociceptive neuraxis or cluster 2 may not have pain primarily because of sensitization, but other factors such as psychosocial ones are involved. CONCLUSION These findings support the notion of shared pathomechanisms irrespective of the pain diagnosis. Conversely, different mechanisms might contribute to the pain of patients with the same diagnosis

Legislative strengthening meets party support in international assistance: a closer relationship?

Recent reports recommend that international efforts to help strengthen legislatures in emerging democracies should work more closely with support for building stronger political parties and competitive party systems. This article locates the recommendations within international assistance more generally and reviews the arguments. It explores problems that must be addressed if the recommendations are to be implemented effectively. The article argues that an alternative, issue-based approach to strengthening legislatures and closer links with civil society could gain more traction. However, that is directed more centrally at promoting good governance for the purpose of furthering development than at democratisation goals sought by party aid and legislative strengtheners in the democracy assistance industry

Sensory phenotypes in complex regional pain syndrome and chronic low back pain-indication of common underlying pathomechanisms.

INTRODUCTION First-line pain treatment is unsatisfactory in more than 50% of chronic pain patients, likely because of the heterogeneity of mechanisms underlying pain chronification. OBJECTIVES This cross-sectional study aimed to better understand pathomechanisms across different chronic pain cohorts, regardless of their diagnoses, by identifying distinct sensory phenotypes through a cluster analysis. METHODS We recruited 81 chronic pain patients and 63 age-matched and sex-matched healthy controls (HC). Two distinct chronic pain cohorts were recruited, ie, complex regional pain syndrome (N = 20) and low back pain (N = 61). Quantitative sensory testing (QST) was performed in the most painful body area to investigate somatosensory changes related to clinical pain. Furthermore, QST was conducted in a pain-free area to identify remote sensory alterations, indicating more widespread changes in somatosensory processing. RESULTS Two clusters were identified based on the QST measures in the painful area, which did not represent the 2 distinct pain diagnoses but contained patients from both cohorts. Cluster 1 showed increased pain sensitivities in the painful and control area, indicating central sensitization as a potential pathomechanism. Cluster 2 showed a similar sensory profile as HC in both tested areas. Hence, either QST was not sensitive enough and more objective measures are needed to detect sensitization within the nociceptive neuraxis or cluster 2 may not have pain primarily because of sensitization, but other factors such as psychosocial ones are involved. CONCLUSION These findings support the notion of shared pathomechanisms irrespective of the pain diagnosis. Conversely, different mechanisms might contribute to the pain of patients with the same diagnosis

Potential thresholds of critically increased cardiac-related spinal cord motion in degenerative cervical myelopathy.

INTRODUCTION New diagnostic techniques are a substantial research focus in degenerative cervical myelopathy (DCM). This cross-sectional study determined the significance of cardiac-related spinal cord motion and the extent of spinal stenosis as indicators of mechanical strain on the cord. METHODS Eighty-four DCM patients underwent MRI/clinical assessments and were classified as MRI+ [T2-weighted (T2w) hyperintense lesion in MRI] or MRI- (no T2w-hyperintense lesion). Cord motion (displacement assessed by phase-contrast MRI) and spinal stenosis [adapted spinal canal occupation ratio (aSCOR)] were related to neurological (sensory/motor) and neurophysiological readouts [contact heat evoked potentials (CHEPs)] by receiver operating characteristic (ROC) analysis. RESULTS MRI+ patients (N = 31; 36.9%) were more impaired compared to MRI- patients (N = 53; 63.1%) based on the modified Japanese Orthopedic Association (mJOA) subscores for upper {MRI+ [median (Interquartile range)]: 4 (4-5); MRI-: 5 (5-5); p < 0.01} and lower extremity [MRI+: 6 (6-7); MRI-: 7 (6-7); p = 0.03] motor dysfunction and the monofilament score [MRI+: 21 (18-23); MRI-: 24 (22-24); p < 0.01]. Both patient groups showed similar extent of cord motion and stenosis. Only in the MRI- group displacement identified patients with pathologic assessments [trunk/lower extremity pin prick score (T/LEPP): AUC = 0.67, p = 0.03; CHEPs: AUC = 0.73, p = 0.01]. Cord motion thresholds: T/LEPP: 1.67 mm (sensitivity 84.6%, specificity 52.5%); CHEPs: 1.96 mm (sensitivity 83.3%, specificity 65.6%). The aSCOR failed to show any relation to the clinical assessments. DISCUSSION These findings affirm cord motion measurements as a promising additional biomarker to improve the clinical workup and to enable timely surgical treatment particularly in MRI- DCM patients. CLINICAL TRIAL REGISTRATION www.clinicaltrials.gov, NCT02170155