Spinothalamic Research Articles

Macromolecular changes in spinal cord white matter characterize whiplash outcome at 1-year post motor vehicle collision

Each year, whiplash injuries from motor vehicle collisions (MVC) affect millions worldwide, with no strong evidence of pathology. While the majority recover soon after the injury, the same is not true for roughly 20% reporting higher levels of pain and distress, without diagnostic options. This study used magnetization transfer (MT) imaging to quantify white matter integrity in 78 subjects with varying levels of pain, 1 year after MVC. MT images of the cervical spinal cord were collected parallel to the intervertebral disks. MT ratios (MTR) were calculated in select white matter tracts along with MTR homogeneity (MTRh) at each level. Significant differences were observed between clinical outcome groups in the left and right spinothalamic tracts (p = 0.003 and 0.020) and MTRh (p = 0.009). MTRh was elevated in females with poor recovery versus females reporting recovery (p < 0.001) or milder symptoms (p < 0.001), and in males reporting recovery (p = 0.007) or no recovery (p < 0.001). There was a significant interaction between recovery status and sex (p = 0.015). MT imaging identified tract specific and regional changes in white matter integrity suggesting potential insults to the cord. Additionally, significant MTRh differences between sexes were observed, characterizing the heterogeneity of whiplash recovery and worse outcomes in females.

Insular responses to transient painful and non-painful thermal and mechanical spinothalamic stimuli recorded using intracerebral EEG

Brief thermo-nociceptive stimuli elicit low-frequency phase-locked local field potentials (LFPs) and high-frequency gamma-band oscillations (GBOs) in the human insula. Although neither of these responses constitute a direct correlate of pain perception, previous findings suggest that insular GBOs may be strongly related to the activation of the spinothalamic system and/or to the processing of thermal information. To disentangle these different features of the stimulation, we compared the insular responses to brief painful thermonociceptive stimuli, non-painful cool stimuli, mechano-nociceptive stimuli, and innocuous vibrotactile stimuli, recorded using intracerebral electroencephalograpic activity in 7 epileptic patients (9 depth electrodes, 58 insular contacts). All four types of stimuli elicited consistent low-frequency phase-locked LFPs throughout the insula, possibly reflecting supramodal activity. The latencies of thermo-nociceptive and cool low-frequency phase-locked LFPs were shorter in the posterior insula compared to the anterior insula, suggesting a similar processing of thermal input initiating in the posterior insula, regardless of whether the input produces pain and regardless of thermal modality. In contrast, only thermo-nociceptive stimuli elicited an enhancement of insular GBOs, suggesting that these activities are not simply related to the activation of the spinothalamic system or to the conveyance of thermal information.

Conditioned pain modulation affects the N2/P2 complex but not the N1 wave: A pilot study with laser-evoked potentials.

The 'pain-inhibits-pain' effect stems from neurophysiological mechanisms involving endogenous modulatory systems termed diffuse noxious inhibitory controls (DNIC) or conditioned pain modulation (CPM). Laser-evoked potentials (LEPs) components, the N2/P2 complex, and the N1 wave, reflect the medial and lateral pain pathway, respectively: anatomically, the lateral thalamic nuclei (LT) project mainly to the somatosensory cortex (N1 generator), while the medial thalamic nuclei (MT) are bound to the limbic cortices (N2/P2 generators). We applied a CPM protocol in which the test stimulus was laser stimulation and the conditioning stimulus was a cold pressor test. LEPs recordings were obtained from 15 healthy subjects in three different conditions: baseline, during heterotopic noxious conditioning stimulation (HNCS) and post-HNCS. We observed a significant reduction in N2/P2 amplitude during HNCS and a return to pre-test amplitude post-HNCS, whereas the N1 wave remained unchanged during and post-HNCS. Our results indicate that CPM affects only the medial pain system. The spinothalamic tract (STT) transmits to both the LT and the MT, while the spinoreticulothalamic (SRT) projects only to the MT. The reduction in the amplitude of the N2/P2 complex and the absence of change in the N1 wave suggest that DNIC inhibition on the dorsal horn neurons affects only pain transmission via the SRT, while the neurons that give rise to the STT are not involved. The N1 wave can be a reliable neurophysiological parameter for assessment of STT function in clinical practice, as it does not seem to be influenced by CPM. No reports have described the effect of DNIC on lateral and medial pain pathways. We studied the N1 wave and the N2/P2 complex to detect changes during a CPM protocol. We found a reduction in the amplitude of the N2/P2 complex and no change in the N1 wave. This suggests that the DNIC inhibitory effect on dorsal horns neurons affects only pain transmission via the SRT, whereas the neurons that give rise to the STT are not involved.

Cervical Cordotomy in Terminal Cancer: Pain Relieving in Oncological Treatment

AbstractCordotomy consists in the discontinuation of the lateral spinothalamic tract (LST) in the anterolateral quadrant of the spinal cord, which aims to reduce the transference of nociceptive information in the dorsal horn of the gray matter of the spinal cord to the somatosensory cortex. The main indication is for patients with terminal cancer that have a low life expectancy. It improves the quality of life by relieving pain. The results are promising and the pain relief rate varies between 69 and 100%. Generally speaking, the complications are mostly temporary and not remarkable.

Quantitative spinal cord MRI in MOG-antibody disease, neuromyelitis optica and multiple sclerosis.

Spinal cord involvement is a hallmark feature of multiple sclerosis, neuromyelitis optica with AQP4 antibodies and MOG-antibody disease. In this cross-sectional study we use quantitative spinal cord MRI to better understand these conditions, differentiate them and associate with relevant clinical outcomes. Eighty participants (20 in each disease group and 20 matched healthy volunteers) underwent spinal cord MRI (cervical cord: 3D T1, 3D T2, diffusion tensor imaging and magnetization transfer ratio; thoracic cord: 3D T2), together with disability, pain and fatigue scoring. All participants had documented spinal cord involvement and were at least 6 months post an acute event. MRI scans were analysed using publicly available software. Those with AQP4-antibody disease showed a significant reduction in cervical cord cross-sectional area (P = 0.038), thoracic cord cross-sectional area (P = 0.043), cervical cord grey matter (P = 0.011), magnetization transfer ratio (P ≤ 0.001), fractional anisotropy (P = 0.004) and increased mean diffusivity (P = 0.008). Those with multiple sclerosis showed significantly increased mean diffusivity (P = 0.001) and reduced fractional anisotropy (P = 0.013), grey matter volume (P = 0.002) and magnetization transfer ratio (P = 0.011). In AQP4-antibody disease the damage was localized to areas of the cord involved in the acute attack. In multiple sclerosis this relationship with lesions was absent. MOG-antibody disease did not show significant differences to healthy volunteers in any modality. However, when considering only areas involved at the time of the acute attack, a reduction in grey matter volume was found (P = 0.023). This suggests a predominant central grey matter component to MOG-antibody myelitis, which we hypothesize could be partially responsible for the significant residual sphincter dysfunction. Those with relapsing MOG-antibody disease showed a reduction in cord cross-sectional area compared to those with monophasic disease, even when relapses occurred elsewhere (P = 0.012). This suggests that relapsing MOG-antibody disease is a more severe phenotype. We then applied a principal component analysis, followed by an orthogonal partial least squares analysis. MOG-antibody disease was discriminated from both AQP4-antibody disease and multiple sclerosis with moderate predictive values. Finally, we assessed the clinical relevance of these metrics using a multiple regression model. Cervical cord cross-sectional area associated with disability scores (B = -0.07, P = 0.0440, R2 = 0.20) and cervical cord spinothalamic tract fractional anisotropy associated with pain scores (B = -19.57, P = 0.016, R2 = 0.55). No spinal cord metric captured fatigue. This work contributes to our understanding of myelitis in these conditions and highlights the clinical relevance of quantitative spinal cord MRI.

Intraoperative Neurophysiology for Optimization of Percutaneous Spinothalamic Cordotomy for Intractable Cancer Pain.

Percutaneous ablation of the cervical spinothalamic tract (STT) remains a therapeutic remedy for intractable cancer pain. However, it is accompanied by the risk of collateral damage to essential spinal cord circuitry, including the corticospinal tract (CST). Recent studies describe threshold-based mapping of the CST with the objective of motor bundle preservation during intramedullary spinal cord and supratentorial surgery. To assess the possibility that application of spinal cord mapping using intraoperative neuromonitoring in percutaneous cordotomy procedures may aid in minimizing iatrogenic motor tract injury. We retrospectively reviewed the files of 11 patients who underwent percutaneous cervical cordotomy for intractable oncological pain. We performed quantitative electromyogram (EMG) recordings to stimulation of the ablation needle prior to the STT-ablative stage. We compared evoked motor and sensory electrical thresholds, and the electrical span between them as a reliable method to confirm safe electrode location inside the STT. Quantified EMG data were collected in 11 patients suffering from intractable cancer pain. The threshold range for evoking motor activity was 0.3 to 1.2 V. Stimulation artifacts were detected from trapezius muscles even at the lowest stimulation intensity, while thenar muscles were found to be maximally sensitive and specific. The minimal stimulation intensity difference between the motor and the sensory threshold, set as "Δ-threshold," was 0.26 V, with no new motor deficit at 3 days or 1 month postoperatively. Selective STT ablation is an effective procedure for treating intractable pain. It can be aided by quantitative evoked EMG recordings, with tailored parameters and thresholds.

Phox2a Defines a Developmental Origin of the Anterolateral System in Mice and Humans

Anterolateral system neurons relay pain, itch, and temperature information from the spinal cord to pain-related brain regions, but the differentiation of these neurons and their specific contribution to pain perception remain poorly defined. Here, we show that most mouse spinal neurons that embryonically express the autonomic-system-associated Paired-like homeobox 2A (Phox2a) transcription factor innervate nociceptive brain targets, including the parabrachial nucleus and the thalamus. We define the Phox2a anterolateral system neuron birth order, migration, and differentiation and uncover an essential role for Phox2a in the development of relay of nociceptive signals from the spinal cord to the brain. Finally, we also demonstrate that the molecular identity of Phox2a neurons is conserved in the human fetal spinal cord, arguing that the developmental expression of Phox2a is a prominent feature of anterolateral system neurons.

Wallerian degeneration in cervical spinal cord tracts is commonly seen in routine T2-weighted MRI after traumatic spinal cord injury and is associated with impairment in a retrospective study

ObjectivesWallerian degeneration (WD) is a well-known process after nerve injury. In this study, occurrence of remote intramedullary signal changes, consistent with WD, and its correlation with clinical and neurophysiological impairment were assessed after traumatic spinal cord injury (tSCI).MethodsIn 35 patients with tSCI, WD was evaluated by two radiologists on T2-weighted images of serial routine MRI examinations of the cervical spine. Dorsal column (DC), lateral corticospinal tract (CS), and lateral spinothalamic tract (ST) were the analyzed anatomical regions. Impairment scoring according to the American Spinal Injury Association Impairment Scale (AIS, A–D) as well as a scoring system (0–4 points) for motor evoked potential (MEP) and sensory evoked potential (SEP) was included. Mann-Whitney U test was used to test for differences.ResultsWD in the DC occurred in 71.4% (n = 25), in the CS in 57.1% (n = 20), and in 37.1% (n = 13) in the ST. With WD present, AIS grades were worse for all tracts. DC: median AIS B vs D, p < 0.001; CS: B vs D, p = 0.016; and ST: B vs D, p = 0.015. More pathological MEP scores correlated with WD in the DC (median score 0 vs 3, p < 0.001) and in the CS (0 vs 2, p = 0.032). SEP scores were lower with WD in the DC only (1 vs 2, p = 0.031).ConclusionsWD can be detected on T2-weighted scans in the majority of cervical spinal cord injury patients and should be considered as a direct effect of the trauma. When observed, it is associated with higher degree of impairment.Key Points• Wallerian degeneration is commonly seen in routine MRI after traumatic spinal cord injury.• Wallerian degeneration is visible in the anatomical regions of the dorsal column, the lateral corticospinal tract, and the lateral spinothalamic tract.• Presence of Wallerian degeneration is associated with higher degree of impairment.

Ventral posterior nucleus volume is associated with neuropathic pain intensity in neuromyelitis optica spectrum disorders

BackgroundNeuropathic pain (NP) is frequent in neuromyelitis optica spectrum disorders (NMOSD). The ventral posterior nucleus (VPN) of the thalamus receives sensory afferences from the spinothalamic tracts and is associated with central pain in other conditions. ObjectiveTo investigate associations between NP and VPN volume in aquaporin-4-IgG- positive (AQP4-IgG+) NMOSD. MethodsThis cross-sectional study included 32 AQP4-IgG+ NMOSD patients and 37 healthy controls. NP intensity was determined by the PainDetect Questionnaire. Spinal cord lesion number and location as well as VPN volume were assessed by MRI, the latter using a multi-atlas-based automated segmentation. ResultsTwenty-five patients (78%) suffered from NP and seven had no pain. Mean VPN volume did not differ between patients with and without NP (p=0.533) or between patients and controls. However, mean VPN volume correlated with average (rho=-0.486, p=0.019) and worst pain intensity (rho=-0.593, p=0.003). Of note, no other thalamic nuclei volumes correlated with measures of pain intensity. Compared to pain-free patients, patients with NP had more lesions involving the thoracic spinal cord (p=0.007). The relationships between VPN and pain intensity measures remained after adjustment for age, myelitis count, and spinal cord lesion location. ConclusionOur data support a model where thoracic spinal cord lesions are associated with the development of NP in AQP4-IgG+ NMOSD and the VPN plays a role in the modulation of NP intensity. VPN volume as assessed in our study may be a clinically meaningful imaging marker of pain severity in AQP4-IgG+ NMOSD.

Accurate Determination of the Cold Detection Threshold with High-Speed Cooling of the Skin.

This study used high-speed cooling of the skin and exact control of stimulus duration to measure the cold detection threshold in healthy participants. The objective was to compare the method of limits, in which the temperature is slowly and gradually increased/decreased until the subject perceives the stimulation, and the method of levels, in which the subject must detect brief thermal stimulations close to the threshold of perception. Twenty healthy volunteers (nine women, 11 men) aged 20-30 years participated in the study. The method of limits and method of levels were performed in all subjects in a counterbalanced order. Four cold detection thresholds were measured with the method of levels, with a temperature ramp of 300°C/sec and stimulus durations of 50 ms, 100 ms, 300 ms, and 500 ms. Three thresholds were measured with the method of limits, with temperature ramps of 1°C/sec, 2°C/sec, and 4°C/sec. On average, the cold detection thresholds were -0.47°C below skin temperature with the method of levels and -1.67°C the method of limits. Interindividual variability was significantly lower with the method of levels than with the method of limits. These results suggest that the method of levels is more accurate than the method of limits for measuring cold detection threshold. The improvement of cold detection threshold measurement may provide new perspectives to more precisely assess the function of A-delta fibers and the spino-thalamic pathway.

Fewer Cardiopulmonary Complications and Shorter Length of Stay in Anterolateral Thoracolumbar Spine Exposures Using a Small-Incision Specialized Retractor System.

Objectives: One of the challenges of spine surgery is the need for adequate exposure of the anterolateral spinal column. Improved retractor systems with integrated lighting minimize the need for large thoracotomy, flank, or abdominal incisions. In 2013, we began using the NuVasive MaXcess® system via a minimal-access lateral incision for thoracic and thoracolumbar spine exposures. These small-access approaches may not offer adequate exposure when bleeding and other complications arise. We sought to determine the feasibility and outcomes of a minimal-access retractor during anterolateral spine exposures. Methods: An institutional-review-board-approved retrospective chart review was performed of all patients who underwent anterolateral thoracic and lumbosacral spine exposure at an academic hospital between December 1999 and April 2017. Cervical and posterior spine exposures were not included. Information regarding patient demographics, comorbid conditions, operative techniques, exposure, estimated blood loss, length of stay, and intraoperative and postoperative complications was collected. Data for standard exposure vs. minimally invasive exposures were compared. Results: Between December 1999 and April 2017, 223 anterolateral spinal exposures were performed at our institution. Of those, 122 (54.7%) patients had true lateral exposures, with 22 (18%) using the minimally invasive retractor. The mean age of our patient population was 57 years (19–89), with 65 (53%) men and a mean body mass index of 29.0 (17.4–58.6). In the standard exposure group, complications occurred in 22 (22%) patients, whereas only two (9%) complications occurred in the minimal-access group. There were no significant differences in overall intraoperative and postoperative complications, except for cardiopulmonary complications, which were reduced in the minimally invasive group (p < 0.019). Patients with minimally invasive exposure had a significantly shorter length of stay than those with standard exposure (7 vs. 13 days, p = 0.001). Conclusions: Minimal-access techniques using advanced retractor systems are both feasible and safe compared to standard techniques allowing for similar lateral spine exposure, but with smaller incisions, fewer cardiopulmonary complications, and shorter lengths of stay.

Conduction velocity of the cold spinal pathway in healthy humans.

We aimed to investigate the conduction velocity of the cold spinal pathway in healthy humans. Using a cold stimulator consisting of micro-Peltier elements that was able to produce steep cooling ramps up to -300°C/s, we recorded cold-evoked potentials after stimulation of the dorsal midline at C5, T2, T6 and T10 vertebral levels and calculated the conduction velocity of the cold spinal pathway. In all participants, we used laser stimulation to deliver painful heat (Aδ-fibres-mediated) and warm (C-fibres-mediated) stimuli to the same sites in order to compare the conduction velocity of the cold spinal pathway with that of the nociceptive and warm spinal pathways. Cold stimulation evoked large-amplitude vertex potentials from all stimulation sites. The mean conduction velocity of the cold spinal pathway was 12.0m/s, which did not differ from that of the nociceptive spinal pathway (10.5m/s). The mean conduction velocity of the warm spinal pathway was 2.0m/s. This study provides previously unreported findings regarding cold spinal pathway conduction velocity in humans that may be useful in the assessment of spinal cord lesions as well as in intraoperative monitoring during spinal surgery. This neurophysiological study provides previously unreported findings on cold spinal pathway conduction velocity in healthy humans. Cold-evoked potentials may represent an alternative to laser-evoked potential recording, useful to assess spinothalamic tract in patients with spinal cord lesions and monitor patients during spinal surgery.

Tailoring of neurosurgical ablative procedures in the management of refractory cancer pain

IntroductionNeurosurgical ablative procedures can offer immediate and effective pain relief for patients suffering from refractory cancer pain. However, choosing the appropriate procedure for each patient may not be straightforward and...

The Effect of Optogenetic Inhibition of the Anterior Cingulate Cortex in Neuropathic Pain Following Sciatic Nerve Injury.

Cortical disinhibition is the underlying pathological alteration contributing to neuropathic pain associated with peripheral nerve injury. Nerve injury resulting in disinhibition of the anterior cingulate cortex has been reported. However, the effect of optogenetic inhibition of the anterior cingulate cortex (ACC) on the sensory component of nerve injury-induced neuropathic pain has not been well studied. To investigate the feasibility of optogenetic ACC modulation, we injected an optogenetic virus or a null virus into the ACC of a nerve injury-induced neuropathic pain model. The unilateral ACC was modulated, and the optogenetic effect was measured by mechanical and thermal sensitivity tests. The assessment was performed in "pre-light off," "stimulation-yellow light on," and "post-light off" states. Optogenetic inhibition of the ACC in injury models revealed improved mechanical and thermal latencies with profound pain-relieving effects against nerve injury-induced neuropathic pain. The sensory thalamic discharge in electrophysiological in vivo recordings was also altered during laser stimulation. This finding indicates that hyperactivity of the ACC in nerve injury increases output to the spinothalamic tract through direct or indirect pathways. The direct photoinhibition of ACC neurons could play a vital role in restoring equilibrium and provide novel insight into techniques that can assuage peripheral nerve injury-induced neuropathic pain.

Tissue bridges predict neuropathic pain emergence after spinal cord injury

ObjectiveTo assess associations between preserved spinal cord tissue quantified by the width of ventral and dorsal tissue bridges and neuropathic pain development after spinal cord injury.MethodsThis retrospective longitudinal study includes...

The Essentials of Brain Anatomy for Physiatrists: Magnetic Resonance Imaging Findings.

Detailed knowledge of the brain anatomy is important for the treatment of patients with brain disorders. In this study, we conducted a review of essential parts of human brain anatomy based on magnetic resonance imaging of the brain. Using T2-weighted brain magnetic resonance imaging, we explained how to recognize several structures in each brain lobe (the frontal, parietal, temporal, and occipital lobes). We depicted the boundary of each structure on brain magnetic resonance imaging and described their functions. The limbic system controls various functions such as emotion, motivation, behavior, memory, and olfaction. Broca's and Wernicke's areas and arcuate fasciculus are important structures for human language functions. Emotion, memory, and language function are one of the main functions of human. Therefore, the anatomical knowledge of the limbic system and language-related structures is important for physiatrists. We described the anatomical location and function of each substructure of the limbic system and language centers. In addition, we indicated the exact points of motor- and sensory-related neural tracts (corticospinal tract, corticoreticular pathway, medial lemniscus, and spinothalamic tract) on brain magnetic resonance imaging. We believe that our review on brain anatomy would be helpful for physiatrists to accurately identify the damage of each function from brain disorders and elucidate proper plan for rehabilitative treatment.

Netrin-1 receptor DCC is required for the contralateral topography of lamina I anterolateral system neurons.

Anterolateral system (AS) neurons relay nociceptive information from the spinal cord to the brain, protecting the body from harm by evoking a variety of behaviours and autonomic responses. The developmental programs that guide the connectivity of AS neurons remain poorly understood. Spinofugal axons cross the spinal midline in response to Netrin-1 signalling through its receptor deleted in colorectal carcinoma (DCC); however, the relevance of this canonical pathway to AS neuron development has only been demonstrated recently. Here, we disrupted Netrin-1:DCC signalling developmentally in AS neurons and assessed the consequences on the path finding of the different classes of spinofugal neurons. Many lamina I AS neurons normally innervate the lateral parabrachial nucleus and periaqueductal gray on the contralateral side. The loss of DCC in the developing spinal cord resulted in increased frequency of ipsilateral projection of spinoparabrachial and spinoperiaqueductal gray neurons. Given that contralateral spinofugal projections are largely associated with somatotopic representation of the body, changes in the laterality of AS spinofugal projections may contribute to reduced precision in pain localization observed in mice and humans carrying Dcc mutations.

Cognitive Fatigue Effects on Physical Performance: The Role of Interoception.

The consensus of opinion, with regard to the effect of cognitive fatigue on subsequent physical performance, is that there is a small, negative effect, but there is no consensus regarding the mechanisms involved. When glucose levels are normal, undertaking cognitive tasks does not induce energy or neurotransmitter depletion. The adenosine hypothesis is questioned as cognitively induced increases in adenosine release are phasic and transient, while persistent effects of adenosine are tonic. Thus, the most likely explanation for a negative effect of cognitive fatigue would appear to be changes in perceptions of effort, for which there is some evidence from subjective participant feedback, while interoceptive theory would suggest a role for motivation levels. Cognitive fatigue and physical fatigue are dependent on interoceptive mechanisms, in particular the interactions between top-down predictions of effort from the dorsolateral prefrontal cortex (PFC) to the insula cortex, anterior cingulate cortex, ventromedial and ventrolateral PFC, and bottom-up feedback from the lamina I spinothalamic pathway, and the vagal and glossopharyngeal medullothalamic pathway. The dopaminergic mesocorticolimbic and the locus coeruleus-noradrenaline pathways are also vital. It would appear that cognitive fatigue leads to different predictions of the expected sensory consequences of undertaking the exercise than in the control condition and there is some evidence that motivation can overcome this. Much more research, in which motivation levels are manipulated, is necessary as the effects are small and the reasons for cognitive fatigue causing changes in predictions of sensory consequences are not clear.

CBD for the treatment of pain: What is the evidence?

Cannabidiol (CBD) has become widely available owing to recent changes in federal and state regulations. Although it is marketed for many health conditions, a recent survey found that the most common reason for taking CBD was for the treatment of pain. The endocannabinoid system (ECS) is present at essentially all levels of the anterolateral system, which is responsible for the perception and modulation of pain. In addition to its effects on the ECS, CBD interacts with other important signaling systems involved in the regulation of pain. Thus, there is a physiological basis to investigate CBD for the treatment of pain. Although CBD has been found to reduce pain in several animal models of inflammatory and neuropathic pain, studies to date lack sufficient rigor to provide more than modest evidence for the analgesic activity of CBD. To date, only 1 controlled clinical study has been published evaluating the effect of CBD in the treatment of pain. This study was fraught with numerous deficiencies in design, such that the results are uninformative. Because studies to date have found a high level of variability in the content of CBD products, product quality is a major concern. Although limited preclinical studies suggest that CBD may alter the metabolism of drugs metabolized by cytochromes P450, the lack of clinical studies makes it impossible to assess the clinical significance of these observations. At present, there is insufficient evidence to recommend CBD for the treatment of pain. The safety of the compound in patients with chronic illness remains untested, and pharmacists should caution patients about its use in the absence of clinical supervision.

Cordotomy for Intractable Cancer Pain: A Narrative Review

Background: Cordotomy is an invasive procedure for the management of intractable pain not controlled by conventional therapies, such as analgesics or nerve block. This procedure involves mechanical disruption of nociceptive pathways in the anterolateral column, specifically the spinothalamic and spinoreticular pathways to relieve pain while preserving fine touch and proprioceptive tracts. Objectives: The purpose of this review article is to refresh our knowledge of cordotomy and support its continued use in managing intractable pain due to malignant disease. Study Design: This is a review article with the goal of reviewing and summarizing the pertinent case reports, case series, retrospective studies, prospective studies, and review articles published from 2010 onward on spinal cordotomy. Setting: The University of Texas, MD Anderson Cancer Center. Methods: PubMed search of keywords “spinal cordotomy,” “percutaneous cordotomy,” or “open cordotomy” was undertaken. Search results were organized by year of publication. Results: Cordotomy can be performed via percutaneous, open, endoscopic, or transdiscal approach. Percutaneous image-guided approach is the most well-studied and reported technique compared with others, with relatively good pain improvement both in the postoperative and shortterm period. The use of open cordotomy has diminished significantly in recent years because of the advent of other less invasive approaches. Cordotomy in children, although rare, has been described in some case reports and case series with reported pain improvement postprocedure. Although complications can vary broadly, some reported side effects include ataxia and paresis due to lesion in the spinocerebellar/corticospinal tract; respiratory failure due to lesion in the reticulospinal tract; or sympathetic dysfunction, bladder dysfunctions, or Horner syndrome due to unintentional lesions in the spinothalamic tract. Limitations: Review article included literature published only in English. For the studies reviewed, the sample size was relatively small and the patient population was heterogeneous (in terms of underlying disease process, duration of symptoms, previous treatment attempted and length of follow-up). Conclusions: Cordotomy results in selective loss of pain and temperature perception on the contralateral side, up to several segments below the level of the disruption. The plethora of analgesics available and advanced technologies have reduced the demand for cordotomy in the management of intractable pain. However, some patients with pain unresponsive to medical and procedural management, particularly malignant pain, may benefit from this procedure, and it is a viable treatment option especially for patients with a limited life expectancy whose severe, unilateral pain is unresponsive to analgesic medications. Key words: Cancer pain, cordotomy complications, cordotomy indications, intractable pain, open cordotomy, percutaneous cordotomy