Chronic Intractable Neuropathic Pain Research Articles

Neat1 lncRNA organizes the inflammatory gene expressions in the dorsal root ganglion in neuropathic pain caused by nerve injury.

Primary sensory neurons regulate inflammatory processes in innervated regions through neuro-immune communication. However, how their immune-modulating functions are regulated in concert remains largely unknown. Here, we show that Neat1 long non-coding RNA (lncRNA) organizes the proinflammatory gene expressions in the dorsal root ganglion (DRG) in chronic intractable neuropathic pain in rats. Neat1 was abundantly expressed in the DRG and was upregulated after peripheral nerve injury. Neat1 overexpression in primary sensory neurons caused mechanical and thermal hypersensitivity, whereas its knockdown alleviated neuropathic pain. Bioinformatics analysis of comprehensive transcriptome changes indicated the inflammatory response was the most relevant function of genes upregulated through Neat1. Consistent with this, upregulation of proinflammatory genes in the DRG following nerve injury was suppressed by Neat1 knockdown. Expression changes of these proinflammatory genes were regulated through Neat1-mRNA interaction-dependent and -independent mechanisms. Notably, Neat1 increased proinflammatory genes by stabilizing its interacting mRNAs in neuropathic pain. Finally, Neat1 in primary sensory neurons contributed to spinal inflammatory processes that mediated peripheral neuropathic pain. These findings demonstrate that Neat1 lncRNA is a key regulator of neuro-immune communication in neuropathic pain.

Paddle-Lead Spinal-Cord Stimulation Surgeries for Chronic Neuropathic Pain: A Single Surgeon Case-Series Outcome Analysis in Indian Population.

Background Spinal-cord stimulation (SCS) for relief of chronic neuropathic pain is well established. Objective The inherent limitations with conventional percutaneous lead SCS are lead migration, positional variations in stimulation, as well as possible nonreplication of benefits after permanent SCS implantation, which were experienced during a positive trial period. To circumvent these limitations, we analyzed five consecutive cases of chronic intractable neuropathic pain who underwent direct SCS paddle lead placement during the trial period for pain relief. In addition, during the process of placing a permanent paddle lead, the impediment created by prior epidural scarring in such chronic patients can be obviated mechanically thereby increasing the efficacy of the procedure. Material and Methods The demographic details, diagnosis, preoperative visual analogue scale score (VAS), and follow-up VAS were recorded. Surgical procedure consisted of a standard dorsal laminotomy followed by placement of permanent paddle leads. Results All patients reported significant improvement in their VAS scores. Mean duration of follow-up was 23.6 months (9-35 months). Mean preoperative VAS was 9.4 and 1.4 at the last follow-up. No major complications were found. Conclusion With careful patient selection and appropriate surgical strategy, it was possible to implant permanent paddle leads during SCS trial itself in our five patients thereby replicating and sustaining the trial period pain relief. We argue that this can be a new cost-effective and reliable technique for the placement of SCS leads achieving excellent and sustained pain relief.

Spinal Cord High-Frequency Stimulation. The Current Experience and Future Directions.

Spinal cord stimulation (SCS) is a neuromodulation technology that has emerged as a valid treatment for chronic intractable neuropathic pain. After conventional tonic SCS, new waveforms of stimulation, like high frequency (HF), have proved that they can provide safe and effective pain relief. In addition, SCS is now being utilized more broadly as a potential treatment for a range of indications, including motor disorders and spasticity. Our study presents a retrospective analysis of 20 patients with heterogenous aetiologies of neuropathic pain treated with HF stimulation, after a standardized protocol in a temporary trial. We observed a significant improvement in pain relief according to comparisons of numerical rating scale (NRS) scores before the procedure, after the clinical trial and at latest follow-up. Two unusual clinical cases were also reported, and the pertinent literature was discussed.

Peripheral Nerve Stimulation in Painful Conditions of the Upper Extremity-An Overview.

Our objective is to present a brief history of the evolution of peripheral nerve stimulation, the current understanding of peripheral nerve stimulation mechanisms in chronic pain, peripheral nerve stimulation applications in upper extremity chronic pain conditions, and complications of peripheral nerve stimulation. The evolution of peripheral nerve stimulation from the early ages to the current status has been facilitated by discoveries in neurobehavioral mechanisms of pain, advances in technology and percutaneous lead development, and the availability of high-quality portable ultrasound units. Peripheral nerve stimulation application in managing upper extremity pain of amputated limbs, post-stroke shoulder pain, complex regional pain syndrome (CRPS), and median, ulnar, and radial neuropathies are discussed. Finally, we describe complications of peripheral nerve stimulation. The availability of ultrasound-guided peripheral nerve stimulation techniques and superior peripheral nerve stimulation technology have opened up new and minimally invasive treatment options for chronic intractable neuropathic pain of the upper extremity. Additionally, the ability to place peripheral nerve stimulation leads percutaneously without open peripheral nerve surgery expands the pool of implanting physicians, while simultaneously decreasing the risks and complications that are associated with open surgery.

Analgesia-enhancing effects of repetitive transcranial magnetic stimulation on neuropathic pain after spinal cord injury:An fNIRS study.

Repetitive transcranial magnetic stimulation (rTMS) is a promising treatment for chronic intractable neuropathic pain in patients with spinal cord injury (SCI). However, the analgesia-enhancing effects of rTMS on conventional interventions (e.g., medications), and the underlying mechanisms remain poorly understood. To investigate the enhancement of analgesia and change of cortex activation by rTMS treatment on neuropathic pain following SCI. A double-blind, sham-controlled, clinical trial was performed. Twenty-one patients with neuropathic pain after SCI were randomized (2:1) to receive a session of rTMS (10 Hz, a total of 1200 pulses at an intensity of 80% resting motor threshold) or sham treatment over the left primary motor cortex (M1) corresponding to the hand area daily for six weeks with a one-day interval per week. At T0 (before rTMS treatment), T1 (after the first session rTMS), T2 (after one week), T3 (after two weeks), T4 (after four weeks) and T5 (after six weeks), activations in the bilateral M1, primary somatosensory cortex (S1), premotor cortex (PMC) and prefrontal cortex (PFC) during the handgrip task were measured using functional near-infrared spectroscopy (fNIRS). In addition, the numerical rating scale (NRS) was used to assess pain. The pain intensity or activation in PFC, PMC, M1 or S1 was not remarkably changed at T1. Along with the time, the pain intensity gradually decreased in both the rTMS and sham groups. The real rTMS, compared with the sham, showed more pain relief from two weeks (T3) to six weeks (T5), and the activations of the motor-related areas M1 and PMC were remarkably suppressed. The findings of this preliminary study with a small patient sample suggest that the analgesia-enhancing effects of high-frequency rTMS might be related with the amelioration of M1 and PMC hypersensitivity, shedding light upon the clinical treatment of SCI-related neuropathic pain.

Unique Characteristics of the Dorsal Root Ganglion as a Target for Neuromodulation.

ObjectiveThe dorsal root ganglion (DRG) is a novel target for neuromodulation, and DRG stimulation is proving to be a viable option in the treatment of chronic intractable neuropathic pain. Although the overall principle of conventional spinal cord stimulation (SCS) and DRG stimulation—in which an electric field is applied to a neural target with the intent of affecting neural pathways to decrease pain perception—is similar, there are significant differences in the anatomy and physiology of the DRG that make it an ideal target for neuromodulation and may account for the superior outcomes observed in the treatment of certain chronic neuropathic pain states. This review highlights the anatomy of the DRG, its function in maintaining homeostasis and its role in neuropathic pain, and the unique value of DRG as a target in neuromodulation for pain.MethodsA narrative literature review was performed.ResultsOverall, the DRG is a critical structure in sensory transduction and modulation, including pain transmission and the maintenance of persistent neuropathic pain states. Unique characteristics including selective somatic organization, specialized membrane characteristics, and accessible and consistent location make the DRG an ideal target for neuromodulation. Because DRG stimulation directly recruits the somata of primary sensory neurons and harnesses the filtering capacity of the pseudounipolar neural architecture, it is differentiated from SCS, peripheral nerve stimulation, and other neuromodulation options.ConclusionsThere are several advantages to targeting the DRG, including lower energy usage, more focused and posture-independent stimulation, reduced paresthesia, and improved clinical outcomes.

The Primary Motor Cortex Stimulation Attenuates Cold Allodynia in a Chronic Peripheral Neuropathic Pain Condition in <i>Rattus norvegicus</i>

Background: The primary motor cortex (M1) stimulation (MCS) is a useful tool for attenuation of the peripheral neuropathic pain in patients with pharmacologically refractory pain. Furthermore, that neurological procedure may also cause antinociception in rodents with neuropathic pain. Cold allodynia is a frequent clinical finding in patients with neuropathic pain, then, we evaluated if an adapted model of neuropathy induced by chronic constriction injury (CCI) of the ischiadicus nervus (sciatic nerve) produces cold allodynia in an animal model of chronic pain. In addition, we also investigated the effect of the electrical stimulation of the M1 on chronic neuropathic pain condition in laboratory animals. Methods: Male Wistar rats were used. An adapted model of peripheral mononeuropathy induced by CCI was carried out by placing a single loose ligature around the right sciatic nerve. The acetone test was used to evaluate the cold allodynia in CCI or Sham (without ligature) rats. The MCS (M1) was performed at low-frequency (20 μA, 100 Hz) during 15 s by deep brain stimulation (DBS-Thomas Recording device) 21 days after CCI or Sham procedures. The cold allodynia was measured before and immediately after the neurostimulation of M1 in the following time-window: 0, 15 and 30 min after MCS. Results: Cold allodynia threshold increased in animals with chronic neuropathic pain submitted to the acetone test 21 days after the CCI surgery. The M1-stimulation by DBS procedure decreased the cold allodynia immediately and until 30 min after M1-stimulation in rats with chronic neuropathic pain. Conclusion: The current proposal for a CCI model by a single loose ligature of the sciatic nerve can be employed as an experimental model of chronic neuropathic pain in rats submitted to peripheral nervous system injury. The M1-stimulation produced antinociception in rats with chronic neuropathic pain. Thus, we reinforced that the MCS decreases cold allodynia in laboratory animals submitted to persistent sciatic nerve constriction and can be a more reasonable procedure for the treatment of chronic intractable neuropathic pain.

Long-Term Results of a Simultaneous Trial of Deep Brain and Motor Cortex Stimulation in Refractory Neuropathic Pain

Objective Although deep brain stimulation (DBS) and motor cortex stimulation (MCS) are effective in patients with refractory neuropathic pain, their application is still empirical; there is no consensus on which technique is better. Methods To enhance the success rate of trial stimulation of invasive neuromodulation techniques and identify approapriate stimulation targets in individual patients, we performed a simultaneous trial of thalamic ventralis caudalis (Vc) DBS and MCS in 11 patients with chronic neuropathic pain and assessed the results of the trial stimulation and long-term analgesia. Results Of the 11 patients implanted with both DBS and MCS electrodes, nine (81.8%) had successful trials. Seven of these nine patients (77.8%) responded to MCS, and two (18.2%) responded to Vc DBS. With long-term follow-up (56 ± 27.5 months), the mean numerical rating scale decreased significantly (P < 0.05). The degree of percentage pain relief in the chronic MCS (n = 7) and chronic DBS (n = 2) groups were 34.1% ± 18.2% and 37.5%, respectively, and there was no significant difference (P = 0.807). Five out of the seven MCS patients (71%) and both DBS patients had long-term success with the treatments, defined as >30% pain relief compared with baseline. Conclusions With simultaneous trial of DBS and MCS, we could enhance the success rate of invasive trials. Considering the initial success rate and the less invasive nature of epidural MCS over DBS, we suggest that MCS may be a better, initial means of treatment in chronic intractable neuropathic pain. Further investigations including other subcortical target-associated medial pain pathways are warranted.

Intrathecal Noggin administration in rats temporally ameliorates mechanical allodynia induced by a chronic constriction injury.

Chronic intractable neuropathic pain after central or peripheral nervous system injury remains refractory to therapeutic intervention. Using microarray and RT-qPCR methods, we found that Noggin mRNA is downregulated in the lumbar enlargement 2 weeks after chronic constriction injury (CCI) in rats.Eight-week-old female Sprague Dawley rats were used for the CCI model. Two weeks after CCI, rats underwent a laminectomy at L5 under halothane anesthesia, and a silicone tube connected to an osmotic minipump was inserted intrathecally for 14 days. Rats were administered Noggin ranging from 10 ng/ml to 10 μg/ml. Phosphate buffered saline (PBS) was used as a control. The time course of mechanical allodynia was assessed for 5 weeks using von Frey filaments. An ANOVA showed that rats administered Noggin at 2 μg/ml had significantly less mechanical allodynia compared with controls.We next compared the effect of intrathecal administration (14 days) of Noggin (2 μg/ml), bone morphogenetic protein 4 (BMP4; 2 μg/ml), or BMP4 (μg/ml) + Noggin (μg/ml) with controls. Only Noggin administration significantly reduced mechanical allodynia in the CCI model.Fluorescence immunohistochemistry indicated that Noggin administration decreased astrocyte accumulation in the dorsal horn compared with PBS after administration for one week. BMP4-driven conversion of oligodendrocyte progenitor cells (OPCs) to type 2 astrocytes is inhibited by Noggin Hampton et al. (2007) . We speculated that Noggin administration inhibits the conversion of OPCs to astrocytes, and decreases glial fibrillar acidic protein expression. This histological condition could decrease neuropathic pain.

Simultaneous Trial of Deep Brain and Motor Cortex Stimulation in Chronic Intractable Neuropathic Pain

Background/Objectives: Both motor cortex stimulation (MCS) and deep brain stimulation (DBS) of the ventralis caudalis (Vc) thalamus have been shown to be effective in chronic neuropathic pain, and the modulation of thalamic and thalamocortical activity is regarded as a possible mechanism. Although Vc DBS and MCS have a common analgesic mechanism, the application of MCS and DBS is still considered empirical, and there is no consensus on which method is better. Methods: We performed a simultaneous trial of thalamic Vc DBS and MCS in 9 patients with chronic neuropathic pain and investigated the results of the stimulation trial and long-term pain relief. Results: Of the 9 patients initially implanted with both DBS and MCS electrodes, 8 (89%) had a successful trial; 6 of these 8 patients (75%) responded to MCS, and the remaining 2 responded to Vc DBS. During the long-term follow-up, the mean numeric rating scale score decreased significantly (p < 0.05). The percentages of pain relief in the chronic MCS group and the chronic DBS group were 37.9 ± 16.5 and 37.5%, respectively, and there was no statistically significant difference (p = 0.157). Conclusion: Considering the initial success rate and the less invasive nature of epidural MCS compared with DBS, we think that MCS would be a more reasonable initial means of treatment for chronic intractable neuropathic pain.

The long-term safety and efficacy of intrathecal therapy using sufentanil in chronic intractable non-malignant pain.

This report describes the long term safety and efficacy of intrathecal therapy using Sufentanil for the management of chronic intractable neuropathic pain in 12 chronic pain patients. Standardized psychological screening was used to determine treatment suitability. Evaluation data included the Visual Analog Scale (VAS), Wong-Baker Faces Scale, Brief Pain Inventory (BPI), Disability of Arm, Shoulder, and Hand (DASH), McGill Quality of Life Questionnaire, and complications (granulomas, toxicity, withdrawal, or deaths). SPSS version 18 was used for data analysis. Pre- and post- treatment BPI measures and pain scale scores showed a statistically significant difference. There were no complications directly related to drug toxicity, nor drug withdrawals, granulomas, or deaths. Intrathecal therapy with Sufentanil therapy offers a good treatment alternative for those cases that have failed both surgery and standard pain treatment. Strict patient selection based on psychological screening, control of co-morbidities, a proper pain management may contribute to successful outcome.

Cognitive Functioning, Emotional Processing, Mood, and Personality Variables Before and After Stereotactic Surgery

Stereotactic central lateral thalamotomy (CLT) has been applied as a treatment for chronic intractable neuropathic pain. However, it is not clear whether this intervention influences the emotional and cognitive impairments observed in patients who have chronic neuropathic pain. To investigate neuropsychological functions and emotional processing in patients with chronic neuropathic pain compared with healthy volunteers and to explore the neuropsychiatric effect of the CLT. We investigated pain ratings, cognitive functions, emotional processes, and personality variables before and after surgery in 8 patients with intractable neuropathic pain. Patients were tested before and 3 months after CLT by the use of neuropsychological tests; clinical scales for depression, anxiety, anhedonia, and anger regulation; a personality test; and 2 experimental tasks testing the theory of mind as well as the ability to recognize facial emotional expressions. Nine age- and sex-matched control subjects were tested once using the same procedure. The comparison of the patient group before surgery with the control group evidenced significant differences on the cognitive assessments, the depression and anxiety scores, as well as on the somatic complaint subscale of the personality test. Three months after CLT, patients experienced a significant improvement in their depression scores. There were no additional postsurgical cognitive impairments. For our patients with chronic neuropathic pain, CLT provided pain relief and reduction of their depression scores without causing postsurgical cognitive impairments.

Spinal cord stimulation reduces hypersensitivity through activation of opioid receptors in a frequency‐dependent manner

Spinal cord stimulation (SCS) is used for the management of chronic intractable neuropathic pain. While used clinically, it is unclear if SCS produces its effects by activation of opioid receptors. The current study aimed to determine if endogenous opioids mediate the analgesia produced by SCS at different frequencies of stimulation in rats with neuropathic pain [spared nerve injury (SNI) model]. Mechanical withdrawal thresholds of the paw were tested before and after 6 h of SCS at different frequencies (4 Hz, 60 Hz and sham) given daily for 4 days at 90% motor threshold 2 weeks after SNI. Rats were given naloxone (3-10 mg/kg/h), naltrindole (1 mg/kg/h) or were made tolerant to morphine (375 g pellets daily), and effects of SCS were tested. A dose of 3 mg/kg/h naloxone prevented the analgesia produced by 4-Hz, but not 60-Hz, SCS; 10 mg/kg/h prevented the analgesia produced by 60-Hz SCS. Naltrindole prevented the analgesia produced by 60-Hz, but not 4-Hz, SCS. In morphine-tolerant rats, 4-Hz SCS had no effect on withdrawal thresholds, but 60-Hz SCS remained effective as seen by increased withdrawal thresholds. These results suggest that both 4- and 60-Hz SCS, in part, work through opioid receptor mechanisms, with 4-Hz SCS activating μ-opioid receptors while 60-Hz SCS activated δ-opioid receptors.

Experimental Spinal Cord Stimulation and Neuropathic Pain: Mechanism of Action, Technical Aspects, and Effectiveness

Spinal cord stimulation (SCS) is a valuable treatment for chronic intractable neuropathic pain. Although SCS has gone through a technological revolution over the last four decades, the neurophysiologic and biochemical mechanisms of action have only been partly elucidated. Animal experimental work has provided some evidence for spinal as well as supraspinal mechanisms of neuropathic pain relief of SCS. A SCS computer model of the electrical properties of the human spinal cord revealed many basic neurophysiologic principles that were clinically validated later on. The main question in clinical SCS is how to further improve the effectiveness of SCS as there is still a significant failure rate of 30%. In this context, experimental studies are needed to elucidate which target pain neuron(s) are involved, as well as with what exact electrical stimulation this target neuron can be influenced to produce an optimal supapression of neuropathic pain. This article reviews the basic clinical and experimental technical aspects in relation to the effectiveness of SCS in view of recent understanding of the dorsal horn pain circuit involved. These data may then result in experiments needed for an improved understanding of the mechanisms underlying SCS and consequently lead to improvement and increased effectiveness of SCS in neuropathic pain as a clinical therapy.

The effects of modulating stimulation parameters of spinal cord stimulation (SCS) and glial activity in animals with neuropathic pain

Spinal cord stimulation is (SCS) is an effective treatment for the management of chronic intractable neuropathic pain. We therefore used an animal model of SCS to modulate frequency (4Hz vs. 60Hz), duration (30m vs. 6h), or intensity (50%, 75%, or 90% MT) in animals with neuropathic pain. To elucidate potential mechanisms modulated by SCS we examined immunoreactivity for glial markers in the spinal cord in animals with SCS compared to those with sham SCS. Neuropathic pain was induced in Sprague-Dawley rats using the spared nerve injury model (SNI).

Estimulación eléctrica medular en pacientes con dolor crónico: evaluación de la discapacidad y la calidad de vida

Introduction Spinal Cord Stimulation (SCS) is a procedure for patients with chronic intractable pain of neuropathic predominance. The objective was to evaluate the disability and quality of life in patients with SCS. Material and methods A retrospective, descriptive and longitudinal research study with 40 male and female patients from 30 to 70 years of age with a SCS system. The intensity of pain was assessed by means of Visual Analogue Scale (VAS), 1 month before and at 6 months after the implant. The Oswestry and the Fast-Espiditest disability indexes were used before and 6 months after the implantation. The statistical analysis of the results was performed using the ANOVA test using a p < 0.05 as significant. Results A total of 88% of patients had neuropathic pain with an aetiological diagnosis of failed back surgery syndrome (67.5%). The baseline VAS score was 8.8 ± 1.1, at 1 month 3.5 ± 2.3 and 3.9 ± 2.0 at the 6th month (p < 0.001). The initial Oswestry Index was 65.5 ± 8.5 and the final one 43.8 ± 11.4 (p < 0.001). Using the Fast-Espiditest 10% of patients had moderate pain and 90% had intense pain at baseline. At 6 months 45% of patients had low pain, 37.5% moderate and 17.5% intense (p < 0.001). Conclusions The SCS is an analgesic alternative for chronic intractable neuropathic pain management. It is a safe and successful technique, improving the disability and quality of life with minimum complications.

Gabapentin for the treatment of chronic intractable neuropathic pain: a long-term follow-up study

Aim of Investigation: Neuropathic pain is caused by functional abnormalities or structural lesions in the peripheral or central nervous systems, and occurs without peripheral nociceptor stimulation. The treatment of neuropathic pain is difficult and done in a variety of ways. This long-term follow-up clinical study investigates efficacy and safety of gabapentin in reducing chronic intractable neuropathic pain, with patients who are resistant to current analgesic treatment regimens or conventional pain therapies. Methods: The investigation was carried out between May 2001 and November 2004. The duration for follow-up of our study was 2 to 43 months. Efficacy was evaluated using four verbal ranking scales, 0–10 for pain intensity, 0–3 for mood profile, 0–3 for quality of sleep, and 0–4 for activity (Eastern Cooperative Oncology Group Scale). Measurements were taken before and after each treatment. Pain quality was assessed with the McGill Pain Questionnaire. Adverse effects and satisfaction (0–4 level scale) were also recorded. Data were analyzed by paired Student's t-test with p < 0.05 considered statistically significant. Results: The 58 enrolled Chinese patients (female: 37, male: 21) had a mean age of 67.2 years (range 45–86) and a history of neuropathic pain unresponsive to conventional medicine. Previous duration of pain was 3 months to 16 years (mean 29.2 ± 41.7 months). Significant improvement (p < 0.0001) was found in initial versus final estimations of pain (9.67 ± 0.96 vs 3.01 ± 1.84), interference of mood (2.5 ± 0.76 vs 0.55 ± 0.54), quality of sleep (2.38 ± 0.99 vs 0.45 ± 0.65), daily activity (1.62 ± 1.14 vs 0.59 ± 0.77), and overall satisfaction with results (3.7 ± 0.53). No significant adverse effects were found when combining gabapentin with amitriptyline (n = 44, 76%) and/or tramadol (n = 24, 41%). Final daily doses were gabapentin 584.5 ± 361.7 mg (range: 100–1800 mg), amitriptyline 27.6 ± 11.9 mg (range: 10–75 mg) and tramadol 216.7 ± 120.4 mg (range: 100–600 mg). Long-term follow-up found these results to continue for 2 to 43 months (9.7 ± 10.9 months). The most frequent adverse effects were dizziness (28%), somnolence (19%) and ataxia (9%). Conclusions: Treatment with gabapentin at low clinical doses combined with low doses of amitriptyline and/or tramadol was found to effectively and safely treat chronic intractable neuropathic pain with few side effects.

Upregulation of the phosphorylated form of CREB in spinothalamic tract cells following spinal cord injury: Relation to central neuropathic pain

Spinal cord injury (SCI) often leads to the generation of chronic intractable neuropathic pain. The mechanisms that lead to chronic central neuropathic pain (CNP) following SCI are not well understood, resulting in ineffective treatments for pain relief. Studies have demonstrated persistent hyperexcitability of dorsal horn neurons which may provide a substrate for CNP. We propose a number of similarities between CNP mechanisms and mechanisms that occur in long-term potentiation, in which hippocampal neurons are hyperexcitable. One biochemical similarity may be activation of the transcription factor, cyclic AMP response element-binding protein (CREB), via phosphorylation (pCREB). The current study was designed to examine whether tactile allodynia that develops in segments rostral to SCI (at-level pain) correlates with an increase in CREB phosphorylation in specific neurons known to be involved in allodynia, the spinothalamic tract (STT) cells. This study determined that, in animals experiencing at-level allodynia 35 days after SCI, pCREB was upregulated in the spinal cord segment rostral to the injury. In addition, pCREB was found to be upregulated specifically in STT cells in the rostral segment 35 days after SCI. These findings suggest one mechanism of maintained central neuropathic pain following SCI involves persistent upregulation of pCREB expression within STT cells.

Longlasting antalgic effects of daily sessions of repetitive transcranial magnetic stimulation in central and peripheral neuropathic pain

Background and objective: A single session of repetitive transcranial magnetic stimulation (rTMS) over motor cortex had been reported to produce short term relief of some types of chronic pain. The...

Number of intrathecal pumps being used for chronic intractable neuropathic pain

The patient with chronic pain that is not well managed by more traditional therapeutic means may be considered for implantation of an intrathecal (IT) pump. The number of patients with chronic intractable pain and the number of patients who have IT pumps in place is not known. In an effort to estimate the number of patients with chronic intractable neuropathic pain treated with IT analgesics, we conducted a retrospective review of a medical claims database. We queried the MEDSTAT’S MarketScan databases which reflect the healthcare experience of employees and dependants covered by health benefit programs of large employers.