Pharmacological Probes to Validate Biomarkers for Analgesic Drug Development.

There is an urgent need for analgesics with improved efficacy, especially in neuropathic and other chronic pain conditions. Unfortunately, in recent decades, many candidate analgesics have failed in clinical phase II or III trials despite promising preclinical results. Translational assessment tools to verify engagement of pharmacological targets and actions on compartments of the nociceptive system are missing in both rodents and humans. Through the Innovative Medicines Initiative of the European Union and EFPIA, a consortium of researchers from academia and the pharmaceutical industry was established to identify and validate a set of functional biomarkers to assess drug-induced effects on nociceptive processing at peripheral, spinal and supraspinal levels using electrophysiological and functional neuroimaging techniques. Here, we report the results of a systematic literature search for pharmacological probes that allow for validation of these biomarkers. Of 26 candidate substances, only 7 met the inclusion criteria: evidence for nociceptive system modulation, tolerability, availability in oral form for human use and absence of active metabolites. Based on pharmacokinetic characteristics, three were selected for a set of crossover studies in rodents and healthy humans. All currently available probes act on more than one compartment of the nociceptive system. Once validated, biomarkers of nociceptive signal processing, combined with a pharmacometric modelling, will enable a more rational approach to selecting dose ranges and verifying target engagement. Combined with advances in classification of chronic pain conditions, these biomarkers are expected to accelerate analgesic drug development.

Intraosseous basivertebral nerve ablation for the treatment of chronic low back pain: a prospective randomized double-blind sham-controlled multi-center study.

PURPOSE: To evaluate the safety and efficacy of radiofrequency (RF) ablation of the basivertebral nerve (BVN) for the treatment of chronic low back pain (CLBP) in a Food and Drug Administration approved Investigational Device Exemption trial. The BVN has been shown to innervate endplate nociceptors which are thought to be a source of CLBP. METHODS: A total of 225 patients diagnosed with CLBP were randomized to either a sham (78 patients) or treatment (147 patients) intervention. The mean age within the study was 47 years (range 25-69) and the mean baseline ODI was 42. All patients had Type I or Type II Modic changes of the treated vertebral bodies. Patients were evaluated preoperatively, and at 2 weeks, 6 weeks and 3, 6 and 12 months postoperatively. The primary endpoint was the comparative change in ODI from baseline to 3 months. RESULTS: At 3 months, the average ODI in the treatment arm decreased 20.5 points, as compared to a 15.2 point decrease in the sham arm (p = 0.019, per-protocol population). A responder analysis based on ODI decrease ≥ 10 points showed that 75.6% of patients in the treatment arm as compared to 55.3% in the sham control arm exhibited a clinically meaningful improvement at 3 months. CONCLUSION: Patients treated with RF ablation of the BVN for CLBP exhibited significantly greater improvement in ODI at 3 months and a higher responder rate than sham treated controls. BVN ablation represents a potential minimally invasive treatment for the relief of chronic low back pain. These slides can be retrieved under Electronic Supplementary Material.

Comprehensive anatomical and immunohistochemical review of the innervation of the human spine and joints with application to an improved understanding of back pain.

BACKGROUND: Pain of spinal origin contributes significantly to cervical, thoracic, and lower back pain presentations. Such pain originates in the nerve fibers supplying the joints or the surrounding ligaments and intervertebral discs. Although there has been little detailed discussion of spinal bony innervation patterns in the literature, the clinical implications of these patterns are anatomically and medically significant. METHODS: The present review provides a detailed analysis of the innervation of the spine, identifying the unique features of each part via online search engines. CONCLUSIONS: The clinical implications of these various studies lie in the importance of the innervation patterns for the mechanism of spinal pain. Immunohistochemical studies have provided further evidence regarding the nature of the innervation of the spine.

Age and gender related neuromuscular changes in trunk flexion-extension.

BACKGROUND: The root mean square surface electromyographic activity of lumbar extensor muscles during dynamic trunk flexion and extension from a standing position and task specific spine ranges of motion objectively assess muscle function in healthy young and middle age individuals. However, literature on neuromuscular activation and associated spine and hip kinematics in older individuals is sparse. This cross sectional study sought to examine the sex and age (<40 versus >60 years) related differences in the neuromuscular activation profiles of the lumbar extensors and the related spine and hip kinematics from healthy individuals during a standardized trunk flexion-extension task. METHODS: Twenty five older (13 females, 60-90 years) and 24 younger (12 females, 18-40 years) healthy individuals performed trunk flexion-extension testing by holding static positions at half-flexion way and full range of motion between standing and maximum trunk flexion. The associated lumbar extensor muscle activity was derived from measurements at standing, half, and maximum flexion positions. The range of motion at the hip and lumbar spine was recorded using 3d accelerometers attached to the skin overlying the multifidus and semispinalis thoracis muscles lateral to the L5 and T4 spinous processes, respectively. Statistical calculations were performed using a permutation ANOVA with bootstrap confidence intervals. RESULTS: The muscle activity in the half related to the maximum flexion position (half flexion relaxation ratio) was significantly smaller in older males when compared with younger males. Moreover, measurements revealed smaller activity changes from standing to the half and from half to the maximum flexion position in older compared to younger individuals. Older males displayed smaller gross trunk range of motion from standing to maximum flexion than any other group. CONCLUSIONS: Gender and normal aging significantly affect both the activation patterns of the lumbar extensor muscles and the kinematics of the trunk during a standardized trunk flexion-extension task. Measurement results from healthy young and middle age individuals should not be used for the assessment of individuals older than 60 years of age.

[Alternating and pulsed magnetic fields for the treatment of dorsopathies].

The therapeutic application of isolated low-intensity magnetic field pulses (magnetic induction 150 mT) results in the significant improvement of the initial tone of microvessels and their vasomotor activity. The application of double pulses of the high-energy magnetic field (magnetic induction 1300 mT per pulse) stimulates the activity of the peripheral neuromuscular apparatus due to an enhancement of the initially low muscular tone and contractility. Moreover, it decreases the degree of manifestation of the functional state of peripheral nerves. These data suggest the necessity of the differential approach to the choice of parameters of the magnetic field being applied taking into account the initial clinical and functional characteristics of neurological dorsopathic syndromes.

Roles of BDNF in spinal neuroplasticity in cats subjected to partial dorsal ganglionectomy.

This study investigated the role of brain-derived neurotrophic factor (BDNF) in neuroplasticity in cats subjected to the removal of dorsal root ganglia (DRG). Following partial ganglionectomy, the number of BDNF-positive varicosities from spared L6 DRG decreased significantly. This reduction was observed at 3 days post operation (dpo) in spinal lamina II of L3 and L5. Whereas the percentages of positive neurons for BDNF and its mRNA in spared L6 DRG at 10 dpo were significantly increased, and accumulated BDNF was seen on the DRG side of the ligated axons. Importantly, BDNF antibody neutralization in vivo results in a significant reduction in the number of varicosities in spinal lamina II, evidenced by BDNF and calcitonin gene-related peptide immunohistochemical staining. These findings suggested that peripheral-derived BDNF could play a critical role in spinal neuroplasticity in cats subjected to partial ganglionectomy. This may underlie the basis of molecular therapy depending on gene drug-like BDNF release.

Is there a relationship between pain intensity and postural sway in patients with non-specific low back pain?

BACKGROUND: Increased center of pressure excursions are well documented in patients suffering from non-specific low back pain, whereby the altered postural sway includes both higher mean sway velocities and larger sway area. No investigation has been conducted to evaluate a relationship between pain intensity and postural sway in adults (aged 50 or less) with non-specific low back pain. METHODS: Seventy-seven patients with non-specific low back pain and a matching number of healthy controls were enrolled. Center of pressure parameters were measured by three static bipedal standing tasks of 90 sec duration with eyes closed in narrow stance on a firm surface. The perceived pain intensity was assessed by a numeric rating scale (NRS-11), an equal number of patients (n = 11) was enrolled per pain score. RESULTS: Generally, our results confirmed increased postural instability in pain sufferers compared to healthy controls. In addition, regression analysis revealed a significant and linear increase in postural sway with higher pain ratings for all included COP parameters. Statistically significant changes in mean sway velocity in antero-posterior and medio-lateral direction and sway area were reached with an incremental change in NRS scores of two to three points. CONCLUSIONS: COP mean velocity and sway area are closely related to self-reported pain scores. This relationship may be of clinical use as an objective monitoring tool for patients under treatment or rehabilitation.

Thoracolumbar interfascial plane block for postoperative analgesia in spine surgery: A systematic review and meta-analysis.

INTRODUCTION: Thoracolumbar interfascial plane (TLIP) block has been discussed widely in spine surgery. The aim of our study is to evaluate analgesic efficacy and safety of TLIP block in spine surgery. METHOD: We performed a quantitative systematic review. Randomized controlled trials that compared TLIP block to non-block care or wound infiltration for patients undergoing spine surgery and took the pain or morphine consumption as a primary or secondary outcome were included. The primary outcome was cumulative opioid consumption during 0-24-hour. Secondary outcomes included postoperative pain intensity, rescue analgesia requirement, and adverse events. RESULT: 9 randomized controlled trials with 539 patients were included for analysis. Compared with non-block care, TLIP block was effective to decrease the opioid consumption (WMD -16.00; 95%CI -19.19, -12.81; p<0.001; I2 = 71.6%) for the first 24 hours after the surgery. TLIP block significantly reduced postoperative pain intensity at rest or movement at various time points compared with non-block care, and reduced rescue analgesia requirement ((RR 0.47; 95%CI 0.30, 0.74; p = 0.001; I2 = 0.0%) and postoperative nausea and vomiting (RR 0.58; 95%CI 0.39, 0.86; p = 0.006; I2 = 25.1%). Besides, TLIP block is superior to wound infiltration in terms of opioid consumption (WMD -17.23, 95%CI -21.62, -12.86; p<0.001; I2 = 63.8%), and the postoperative pain intensity at rest was comparable between TLIP block and wound infiltration. CONCLUSION: TLIP block improved analgesic efficacy in spine surgery compared with non-block care. Furthermore, current literature supported the TLIP block was superior to wound infiltration in terms of opioid consumption.

Spinal reflexes in the long-tailed stingray, Himantura fai.

We have exploited the segregation of motor and sensory axons into peripheral nerve sub-compartments to examine spinal reflex interactions in anaesthetized stingrays. Single, supra-maximal electrical stimuli delivered to segmental sensory nerves elicited compound action potentials in the motor nerves of the stimulated segment and in rostral and caudal segmental motor nerves. Compound action potentials elicited in segmental motor nerves by single stimuli delivered to sensory nerves were increased severalfold by prior stimulation of adjacent sensory nerves. This facilitation of the segmental reflex produced by intense conditioning stimuli decreased as it was applied to more remote segments, to approximately the same degree in up to seven segments in the rostral and caudal direction. In contrast, an asymmetric response was revealed when test and conditioning stimuli were delivered to different nerves, neither of which was of the same segment as the recorded motor nerve: in this configuration, conditioning volleys generally inhibited the responses of motoneurons to stimuli delivered to more caudally located sensory nerves. This suggests that circuitry subserving trans-segmental interactions between spinal afferents is present in stingrays and that interneuronal connections attenuate the influence that subsequent activity in caudal primary afferents can have on the motor elements.

Thoracoscopic sympathectomy.

With the advent of videotechnology, sympathectomy has assumed a more important role in the armamentarium of managing diseases of the autonomic system. Currently it is used primarily for hyperhydrosis, although sympathectomy for reflex sympathetic dystrophy (RSD), Raynaud disease and other diseases still are performed, but less frequently. Most of this article will refer primarily to hyperhydrosis patients.

Associations between Age-Related Changes in the Core Vestibular Projection Pathway and Balance Ability: A Diffusion Tensor Imaging Study.

OBJECTIVE: We investigated the changes of the vestibulospinal tract (VST) and parietoinsular vestibular cortex (PIVC) using diffusion tensor imaging (DTI) and relation to balance between old and young healthy adults. METHODS: This study recruited eleven old adults (6 males, 5 females; mean age 63.36 ± 4.25 years) and 12 young adults (7 males, 5 females; mean age 28.42 ± 4.40 years). The lateral and medial VST and PIVC were reconstructed using DTI. Fractional anisotropy (FA), mean diffusivity (MD), and tract volume were measured. The six-minute walk test (6-MWT), the timed up and go test (TUG), and the Berg balance scale (BBS) were conducted. Spatiotemporal parameters during tandem gait and values of sway during one-leg standing using the wearable sensors were measured. All parameters between two groups were analyzed by the Mann-Whitney U test and independent t-test. RESULTS: Statistically significant decrease in old adults was detected in the tract volume of lateral (p = 0.005) and medial VST (p = 0.005) and medial VST (p = 0.005) and medial VST (p = 0.005) and medial VST (p = 0.005) and medial VST (p = 0.005) and medial VST (p = 0.005) and medial VST (p = 0.005) and medial VST (p = 0.005) and medial VST (p = 0.005) and medial VST (p = 0.005) and medial VST (p = 0.005) and medial VST (p = 0.005) and medial VST (p = 0.005) and medial VST (p = 0.005) and medial VST (. CONCLUSION: The results suggested that there was a relationship between DTI parameters in the vestibular neural pathway and balance according to aging.

Efficacy and safety of paravertebral block versus intercostal nerve block in thoracic surgery and breast surgery: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the analgesic efficacy and safety of paravertebral block (PVB) versus intercostal nerve block (INB) in thoracic surgery and breast surgery. METHODS: The PubMed, Web of Science, Embase and the Cochrane Library were searched up to February 2020 for all available randomized controlled trials (RCTs) that evaluated the analgesic efficacy and safety of PVB compared with INB after thoracic surgery and breast surgery. For binary variables, odds ratio (OR) and 95% confidence interval (CI) was used. For continuous variables, weighted mean difference (WMD) and 95% confidence interval (CI) were used. RevMan5. 3 and Stata/MP 14.0 were used for performing the meta-analysis. RESULTS: A total of 9 trials including 440 patients (PVB block:222 patients; INB: 218 patients) met the inclusion criteria. In the primary outcome, there was no significant differences between the two groups with respect to postoperative visual analogue scale (VAS) at 1h (Std. MD = -0. 20; 95% CI = -1. 11to 0. 71; P = 0. 66), 2h (Std. MD = -0. 71; 95% CI = -2. 32to 0. 91; P = 0. 39), 24h (Std. MD = -0. 36; 95% CI = -0. 73 to -0. 00; P = 0. 05) and 48h (Std. MD = -0. 04; 95% CI = -0. 20 to 0. 11; P = 0. 57). However, there was significant difference in VAS of non Chinese subgroup at 1h (Std. MD = 0. 33; 95% CI = 0. 25to 0. 41; P<0. 00001) and VAS of Chinese subgroup at 24h (Std. MD = -0.32; 95% CI = -0.49 to-0.14; P = 0.0003). In the secondary outcome, the analysis also showed no significant difference between the groups according to the rates of postoperative nausea and vomit (OR = 0. 63; 95% CI = 0. 38 to 1. 03; P = 0. 06) and the rates of postoperative additional analgesia (OR = 0. 57; 95% CI = 0. 21 to 1. 55; P = 0. 27). There was significant difference in postoperative consumption of morphine (Std. MD = -14. 57; 95% CI = -26. 63 to -0.25; P = 0. 02). CONCLUSION: Compared with INB, PVB can provide better analgesia efficacy and cause lower consumption of morphine after thoracic surgery and breast surgery.

Diagnosis of lumbar radiculopathy using simultaneous MR neurography and apparent T2 mapping.

We sought to assess the utility of simultaneous apparent T2 mapping and neurography with the nerve-sheath signal increased by inked rest-tissue rapid acquisition of relaxation-enhancement imaging (SHINKEI-Quant) for the quantitative evaluation of compressed nerves in patients with lumbar radiculopathy. Thirty-two patients with lumbar radiculopathy and 5 healthy subjects underwent simultaneous apparent T2 mapping and neurography with SHINKEI-Quant. Regions of interest (ROIs) were placed in the lumbar dorsal root ganglia (DRG) and the spinal nerves distal to the lumbar nerves bilaterally at L4-S1. The T2 relaxation times were measured on the affected and unaffected sides. The T2 ratio was calculated as the affected side/unaffected side. Pearson correlation coefficients were calculated to determine the correlation between the T2 relaxation times or T2 ratio and clinical symptoms. An ROC curve was used to examine the diagnostic accuracy and threshold of the T2 relaxation times and T2 ratio. We observed no significant differences in the T2 relaxation times between the nerve roots on the left and right at each spinal level in healthy subjects. In patients, lumbar neurography revealed swelling of the involved nerve, and prolonged T2 relaxation times compared with that of the contralateral nerve. The T2 ratio correlated with leg pain. The ROC analysis revealed that the T2 relaxation time threshold was 127 ms and the T2 ratio threshold was 1.07. To our knowledge, this is the first study to show the utility of SHINKEI-Quant for the quantitative evaluation of lumbar radiculopathy.

Regenerating Corticospinal Axons Innervate Phenotypically Appropriate Neurons within Neural Stem Cell Grafts.

Neural progenitor cell grafts form new relays across sites of spinal cord injury (SCI). Using a panel of neuronal markers, we demonstrate that spinal neural progenitor grafts to sites of rodent SCI adopt diverse spinal motor and sensory interneuronal fates, representing most neuronal subtypes of the intact spinal cord, and spontaneously segregate into domains of distinct cell clusters. Host corticospinal motor axons regenerating into neural progenitor grafts innervate appropriate pre-motor interneurons, based on trans-synaptic tracing with herpes simplex virus. A human spinal neural progenitor cell graft to a non-human primate also received topographically appropriate corticospinal axon regeneration. Thus, grafted spinal neural progenitor cells give rise to a variety of neuronal progeny that are typical of the normal spinal cord; remarkably, regenerating injured adult corticospinal motor axons spontaneously locate appropriate motor domains in the heterogeneous, developing graft environment, without a need for additional exogenous guidance.

Comparison between ultrasound-guided paravertebral nerve block and subarachnoid block for elderly male patients under unilateral-opened inguinal hernia repair operation: A randomised controlled trial.

BACKGROUND: Paravertebral block (PVB) as a sole anesthetic technique is difficult even in experienced hands. Hence, this study was undertaken to study the safety and efficacy of PVB and to compare with subarachnoid block (SAB) for inguinal hernia repair surgery (IHRS) in elderly male patients. MATERIALS AND METHODS: Sixty-five male patients aged 65 to 89 scheduled for IHRS were allocated randomly by computer-generated randomisation sequence into two groups. They underwent PVB (Group PVB: 33 patients were injected with 10 ml ropivacaine 0.5% at each level from T12 to L1) or SAB (Group SAB: 32 patients were injected with 15 mg ropivacaine 0.5% at L3-L4 level). Primary outcomes were hemodynamic changes and duration of postoperative analgesia. Secondary outcomes were dosage of remedial analgesics, time to perform the block, side effects and satisfaction of patients. RESULTS: The hemodynamics in the Group PVB were more stable than those in the Group SAB during surgery (P < 0.05). The duration of post-operative analgesia was significantly longer in the Group PVB (P < 0.001). The total dose of fentanyl was smaller in the Group PVB in the first 24 h (P < 0.001). The time to perform the block was significantly longer in the Group PVB (P < 0.001). There was a significant difference in the visual analogue scales (VAS) scores between the two groups at 4 h, 6 h, 8 h and 10 h (P < 0.05) but not at 2 h, 12 h and 24 h (P > 0.05). The VAS scores were lowest at 2 h for both the 2 groups, highest at 12 h for Group PVB and at 8 h for Group SAB respectively. The Group PVB had fewer adverse effects (P < 0.05) and higher satisfaction of patients (P < 0.05). CONCLUSION: Ultrasound-guided PVB can ensure the anesthetic effects of unilateral-opened IHRS in elderly male patients. It has a small impact on hemodynamics, a longer postoperative analgesia time and less complications.

Paraspinal and limb motor neuron involvement within homologous spinal segments in ALS.

OBJECTIVE: We studied the involvement of motor neuron groups innervating paraspinal muscles in amyotrophic lateral sclerosis (ALS) and evaluated the value of paraspinal muscle EMG in the diagnosis of the disease. METHODS: We used quantitative concentric needle EMG to study denervation and reinnervation in a paraspinal muscle and a limb muscle innervated by the C6 and L5 segments in 32 patients with ALS. As control subjects we studied 11 patients with peripheral neuropathy, and 46 non-neurogenic control subjects. RESULTS: We found similar abnormalities in motor-unit potentials (MUPs) in paraspinal and limb muscles in these two segments in ALS. Fasciculation potentials (FPs) were more frequent in limb muscles than in paraspinal muscles and fibrillations and sharp waves (fibs-sw) were most frequent in tibialis anterior. In peripheral neuropathy paraspinal muscles were normal but tibialis anterior showed very abnormal motor unit potentials. CONCLUSIONS: These results are consistent with generalised involvement of motor neurons in motor neuron pools in spinal segments in early stages of ALS progression. However, distally predominant fibrillations indicate susceptibility to ongoing denervation in reinnervated distal axons. Complex FPs of similar morphology to MUP analysis in the same early affected muscle suggests a proximal origin for these FPs at this phase. SIGNIFICANCE: Our observations emphasize the value of paraspinal muscle EMG in the electrophysiological diagnosis of ALS.

Neurophysiological basis of rehabilitation of adolescent idiopathic scoliosis.

BACKGROUND: Knowledge on mechanisms of neurophysiological control of trunk movement and posture could help in the development of rehabilitation programs and brace treatment in adolescent idiopathic scoliosis (AIS). AIMS: Reviewing up-to-date research on neurophysiology of movement and posture control with the aim of providing basis for new researches in the field of AIS rehabilitation and background understanding for clinicians engaged in management of AIS. METHODS: Review of literature. RESULTS: We considered several neurophysiological issues relevant for AIS rehabilitation, namely, the peculiar organization of patterns of trunk muscle recruitment, the structure of the neural hardware subserving axial and arm muscle control, and the relevance of cognitive systems allowing mapping of spatial coordinates and building of body schema. DISCUSSION AND CONCLUSION: We made clear the reason why trunk control is generally carried out by means of very fast, feedforward or feedback driven patterns of muscle activation which are deeply rooted in our neural control system and very difficult to modify by training. We hypothesized that augmented sensory feedback and strength exercises could be an important stage in a rehabilitation program aimed at hindering, or possibly reversing, scoliosis progression. In this context we considered bracing not only as a corrective biomechanical device but also as a tool for continuous sensory stimulation that could help awareness of body misalignment. Future research aimed at developing strategies of trunk postural control learning is essential in the rehabilitation of adolescent idiopathic scoliosis.

High contrast between lumbar nerve roots and surrounding structures using dual echo 3D turbo spin echo additional fusion images.

PURPOSE: We performed lumbar spinal magnetic resonance imaging of three-dimensional (3D) dual echo volumetric isotropic turbo spin echo acquisition (DE-VISTA) and constructed DE-VISTA additional fusion images (DE-VISTA-AFI), which is the addition of DE-VISTA proton density-weighted images (DE-VISTA-PDWI) to DE-VISTA T2-weighted images (DE-VISTA-T2WI). The aim of this study was to clarify whether DE-VISTA-AFI was able to clearly delineate spinal nerve roots. METHODS: A total of 677 patients underwent lumbar MR imaging, and the signal ratio (SR) between cerebrospinal fluid and nerve roots inside the dural sac and the SR between fat and nerve roots outside the dural sac were estimated using DE-VISTA-AFI, DE-VISTA-PDWI, DE-VISTA-T2WI, and 2D-T2WI. RESULTS: The SR between cerebrospinal fluid and nerve roots inside the dural sac on DE-VISTA-AFI was higher than that on DE-VISTA-PDWI (p < 0.0001) and on 2D T2WI (p < 0.0001). The SR between the fat tissue and nerve roots outside the dural sac on DE-VISTA-AFI was higher than that on DE-VISTA-PDWI (p < 0.0001) and 2D T2WI (p < 0.0001). CONCLUSION: DE-VISTA-AFI could clearly delineate the entire length of the lumbar nerve roots that run from the cauda equina in the spinal fluid through to the fat in the lateral recess, intervertebral foramen, and outside the intervertebral foramen.

Role of reflex gain and reflex delay in spinal stability--a dynamic simulation.

The goal of this study was to investigate the role of reflex and reflex time delay in muscle recruitment and spinal stability. A dynamic biomechanical model of the musculoskeletal spine with reflex response was implemented to investigate the relationship between reflex gain, co-contraction, and stability in the spine. The first aim of the study was to investigate how reflex gain affected co-contraction predicted in the model. It was found that reflexes allowed the model to stabilize with less antagonistic co-contraction and hence lower metabolic power than when limited to intrinsic stiffness alone. In fact, without reflexes there was no feasible recruitment pattern that could maintain spinal stability when the torso was loaded with 200N external load. Reflex delay is manifest in the paraspinal muscles and represents the time from a perturbation to the onset of reflex activation. The second aim of the study was to investigate the relationship between reflex delay and the maximum tolerable reflex gain. The maximum acceptable upper bound on reflex gain decreased logarithmically with reflex delay. Thus, increased reflex delay and reduced reflex gain requires greater antagonistic co-contraction to maintain spinal stability. Results of this study may help understanding of how patients with retarded reflex delay utilize reflex for stability, and may explain why some patients preferentially recruit more intrinsic stiffness than healthy subjects.

Anatomy and examination of the spine.

A basic knowledge of anatomy of the spine is an essential ingredient to understanding disease and disorders of the spine. The second section of this article details the neurologic examination of the spine in patients with neck and back pain. Understanding anatomic concepts leads to an informed examination of the spine. Through the history and neurologic examination, many disorders of spinal anatomy can be diagnosed.