Sang-Ho Ahn

Gabapentin effect on neuropathic pain compared among patients with spinal cord injury and different durations of symptoms.

STUDY DESIGN This study evaluated the effect of gabapentin on neuropathic pain in patients with spinal cord injury. OBJECTIVE To compare the effect of gabapentin on neuropathic pain refractory to conventional analgesics in patients with spinal cord injury and different durations of symptoms. SUMMARY OF BACKGROUND DATA Neuropathic pain in patients with spinal cord injury severely compromises their quality of life. Gabapentin is a new antiepileptic drug that may additionally have a role in the treatment of neuropathic pain. So far, there has been little prospective research investigating the effect of gabapentin on neuropathic pain in patients after spinal cord injury or comparing gabapentin-treated patients with varying durations of symptoms after spinal cord injury. METHODS The study included 31 patients who had experienced neuropathic pain associated with spinal cord injury or cauda equina syndrome. These subjects were divided into two groups. Group 1 (n = 13) was composed of patients whose duration of pain was less than 6 months, and Group 2 (n = 18) comprised patients whose symptoms of neuropathic pain had lasted more than 6 months. Although these patients had been treated with conventional analgesics such as antidepressants, anticonvulsants, membrane stabilizer, and neuroleptics, they reported that their condition did not improve after a medication trial of at least 2 weeks duration. In this study, conventional analgesics were continued at a therapeutic level, and gabapentin was administrated for an 18-day titration period followed by a 5-week maintenance period at a dosage of 1800 mg/day or the maximum tolerable dosage. The efficacy of gabapentin administration was gauged by a pain score and a sleep interference score using a 100-mm visual analogue scale (VAS) every 2 weeks. The scores of the two groups were compared every 2 weeks over the course of the 8-week study. RESULTS The mean pain score and the mean sleep interference score for Group 1 decreased more than that of Group 2 during the interval between 2 to 8 weeks (P < 0.05). The mean pain score for Group 1 decreased from 7.3 +/- 0.5 initially to 3 +/- 0.6 after 8 weeks of treatment, whereas the corresponding score for Group 2 decreased from 7.6 +/- 0.4 to 5.1 +/- 0.6 ( < 0.05). The mean sleep interference score for Group 1 decreased from 5.7 +/- 0.9 initially to 1.8 +/- 0.8 after 8 weeks of treatment, whereas the corresponding score for Group 2 decreased from 5.9 +/- 0.8 to 4.2 +/- 0.7 (P < 0.05). As compared with the onset of this study, a decrease in pain score of 2 or more was reported at the completion of this study for 11 patients (100%) in Group 1 and 10 (71%) of 14 patients in Group 2. A decrease of 2 or more in sleep interference scores was reported for 8 (89%) of 9 patients with sleep interference in Group 1 and for 8 (62%) of 13 patients with sleep interference in Group 2. Some adverse effects such as somnolence were noted, but they were mild or moderate in intensity. CONCLUSIONS Gabapentin may be effective in decreasing neuropathic pain refractory to conventional analgesics in some patients with spinal cord injury whose duration of symptoms is less than 6 months, although those with duration of symptoms longer than 6 months showed a significant decrease as well. The drug is unlikely to cause serious adverse effects that limit its use in patients with spinal cord injury.

Changes in expression of mRNA for interleukin-8 and effects of interleukin-8 receptor inhibitor in the spinal dorsal horn in a rat model of lumbar disc herniation.

Study Design. Autologous nucleus pulposus obtained from coccygeal intervertebral discs was grafted on the proximal of L5 dorsal root ganglion. Pain behavior, mRNA expression of Interleukin-8 (IL-8), and immunohistochemical changes were assessed. Objective. The purpose of this study is to investigate temporal changes of IL-8 expression in the spinal cord and dorsal root ganglion and the pain-related behaviors with time course and to elucidate whether repertaxin (IL-8 receptor inhibitor) attenuates pain-related behaviors in a rat model of lumbar disc herniation. Summary of Background Data. Inflammatory mediators like cytokines and chemokines have been implicated in radicular pain because of disc herniation. IL-8, known as CXCL8, is a chemokine, which has been reported to be associated with painful degenerative disc disorders and chronic inflammatory pain states. Methods. Lumbar disc herniated rat model was made by implantation of the autologous nucleus pulposus, harvested from the coccygeal vertebra of each tail, on the left L5 nerve root just proximal to thedorsal root ganglion. Rats were tested for mechanical allodynia and thermal hyperalgesia at 2 days before surgery, and on days 1, 5, 10, 20, 30, 40, 50, and 60 postoperatively. Experimental group was intrathecally injected with the IL-8 receptor inhibitor at L5 level on postoperative day 10. Mechanical allodynia of the plantar surface of both hindpaw was tested on 30 minutes, 1, 3 hours, 1, 3, 5, and 10 days after administration. For the staining of astrocytes and microglia, immunohistochemical study was done 20 days after surgery. Results. Mechanical allodynia in ipsilateral hindpaw developed 1 day after surgery and lasted until 60 days and thermal withdrawal latency decreased significantly on the ipsilateral side 10 days after surgery and gradually increased through day 60. The IL-8 receptor inhibitor attenuated the mechanical allodynia caused by nucleus pulposus when it was administered on postoperative day 10 and reduced microglial activation and phosphorylated form of mitogen-activated protein kinase (pERK) expression in the spinal dorsal horn. Conclusion. IL-8 might be a potential therapeutic target in chronic radicular neuropathic pain because of disc herniation, CXCL8 inhibitor could be one of its promising therapeutic agents.

Changes in Spinal Cord Expression of Fractalkine and its Receptor in a Rat Model of Disc Herniation by Autologous Nucleus Pulposus

Study Design. Behavior, mRNA and immunohistochemical assessment of the expression of fractalkine (CX3CL1) and its receptor (CX3CR1) in a rat model of disc herniation by autologous nucleus pulposus (NP) implantation. Objective. To evaluate the changes in expression of fractalkine and its receptor in the spinal cord and their association with pain behavior in a rat model of disc herniation. Summary of Background Data. Chemokines have recently been implicated in the pathophysiology of neuropathic pain. They mediate astrocytic migration and microglial proliferation, which are involved in the regulation of nociceptive transmission. Fractalkine is a chemokine, which participates in the mechanisms of neuropathic pain as a mediator of neuron–glia interactions. Methods. Sixty-six rats (NP-treated = 47, sham = 19) were implanted with autologous NP (approximately 3 mg) on the left L5 nerve root, just proximal to the dorsal root ganglion and tested for thermal hyperalgesia and mechanical allodynia before surgery and on days 1, 5, 10, 20, and 30 after surgery. The changes of expression of fractalkine and its receptor in the spinal cord were studied using real time PCR and immunohistochemistry. Results. Rats developed ipsilateral mechanical allodynia at day 1 and bilateral thermal hyperalgesia at day 5 after surgery, and these changes in sensitivity persisted throughout the observation period. The expression of mRNA for fractalkine in the spinal cord was increased by day 5 and remained upregulated for the duration of the experiment. The immunostaining for fractalkine increased in neurons and astrocytes and that for the fractalkine receptor increased in microglia in the dorsal horn ipsilateral to the disc herniation. Conclusion. Our results indicate that autologous implantation of NP induces thermal hyperalgesia and mechanical allodynia, and leads to an upregulation of fractalkine and its receptor in spinal neurons and glia, implicating fractalkine in association with radicular pain.

Abnormal spontaneous activities on needle electromyography and their relation with pain behavior and nerve fiber pathology in a rat model of lumbar disc herniation.

Study Design. This longitudinal experimental study was conducted to investigate electrophysiologic characteristics, pain behavior, and histological changes in a rat model of lumbar disc herniation. Objective. To observe abnormal spontaneous activity (ASA) on needle electromyography (EMG) and to determine its relation with neuropathic pain behavior and histological changes longitudinally in a rat model of lumbar disc herniation. Summary of Background Data. Needle EMG is generally performed to determine the existence and the degree of radiculopathy caused by disc herniation. The local application of autologous nucleus pulposus to the spinal nerve has been shown to induce neuropathic pain. However, little is known about the relations between neuropathic pain and abnormal EMG findings and the manner in which they change with time in rat models of lumbar disc herniation. Methods. Twenty-five Sprague-Dawley rats were randomly assigned to either sham or experimental groups. In the experimental group, autologous nucleus pulposus was grafted on the left L5 dorsal root ganglion. All rats were evaluated for mechanical allodynia and thermal hyperalgesia and underwent needle EMG examinations before and on days 1, 5, 10, 20, 30, 40, and 50 after surgery. Morphologic changes of L5 spinal nerves and of sciatic nerves were assessed by toluidine blue staining on days 1, 5, and 50 after surgery. Results. A dramatic decrease in mechanical withdrawal threshold and in thermal withdrawal latency was observed on day 1 after surgery, and these changes persisted until day 50 after surgery. ASAs on needle EMG were observed on day 1 (33%), peaked on day 5 (93%), and gradually decreased from day 10 (69%) to day 40 (18%) after surgery. Pathologic findings of nerve fibers, such as swelling of myelin sheaths, demyelination, and degeneration of axoplasms were observed from day 1. These findings were exaggerated on day 5 and then diminished but were still evident on day 50. Conclusion. Neuropathic pain and pathologic changes in spinal nerve fibers probably remain even after ASAs in EMG have disappeared in our rat model of lumbar disc herniation. These results provide baseline data concerning the natural courses of electrophysiologic findings and of radicular pain in patients with intervertebral disc herniation.

Attenuation of Spinal Cord Injury-Induced Astroglial and Microglial Activation by Repetitive Transcranial Magnetic Stimulation in Rats

Spinal cord injury (SCI) causes not only loss of sensory and motor function below the level of injury but also chronic pain, which is difficult and challenging of the treatment. Repetitive transcranial magnetic stimulation (rTMS) to the motor cortex, of non-invasive therapeutic methods, has the motor and sensory consequences and modulates pain in SCI-patients. In the present study, we studied the effectiveness of rTMS and the relationship between the modulation of pain and the changes of neuroglial expression in the spinal cord using a rat SCI-induced pain model. Elevated expressions of Iba1 and GFAP, specific microglial and astrocyte markers, was respectively observed in dorsal and ventral horns at the L4 and L5 levels in SCI rats. But in SCI rats treated with 25 Hz rTMS for 8 weeks, these expressions were significantly reduced by about 30%. Our finding suggests that this attenuation of activation by rTMS is related to pain modulation after SCI. Therefore, rTMS might provide an alternative means of attenuating neuropathic pain below the level of SCI.

Pulsed Radiofrequency Application Reduced Mechanical Hypersensitivity and Microglial Expression in Neuropathic Pain Model

OBJECTIVE Pulsed radiofrequency (PRF) procedure has been used in clinical practice for the treatment of chronic neuropathic pain conditions without neuronal damage. The purpose of this study was to investigate the changes in pain response and glial expression after the application of PRF on a dorsal root ganglion (DRG) in a neuropathic pain model. DESIGN A neuropathic pain model (14 female Sprague-Dawley [SD] rats; 200-250 g) was made by a unilateral L5 spinal nerve ligation (SNL) and transection on the distal side of the ligation. The development of mechanical and cold hypersensitivity on the hindpaw was established postoperative day 9 (POD 9). The rats were then randomly assigned to the PRF (+) and the PRF (-) groups. Furthermore, PRF (2 bursts/s, duration = 20 milliseconds, output voltage = 45 V) was applied on the ipsilateral DRG for 180 seconds, with a maximum temperature of 42°C, at POD 10. Pain behaviors were tested throughout the 12 days after PRF. We also examined the changes of the spinal glial expression by immunohistochemistry. RESULTS Significant reduction of mechanical hypersensitivity in the PRF (+) group was observed from day 1 after a single PRF procedure and was maintained throughout the following 12 days. Immunoreactivity for OX42 in the ipsilateral dorsal horn also decreased compared with that of the PRF (-) group. However, cold hypersensitivity and glial fibrillary acidic protein (GFAP) immunoreactivity in the dorsal horn was not affected by a PRF procedure. CONCLUSIONS Our result demonstrated that the mechanical hypersensitivity, induced by L5 SNL, was attenuated by a PRF procedure on the ipsilateral DRG. This analgesic effect may be associated with an attenuation of the microglial activation in the dorsal horn.

Salivagram after gland injection of botulinum neurotoxin A in patients with cerebral infarction and cerebral palsy.

Pulmonary aspiration in patients with brain lesions may result from dysfunction of theswallowing process or gastroesophageal reflux. Inadequate protection of the airway fromoral secretions such as saliva may also induce aspiration. Chronic pulmonary aspiration ofsaliva can lead to substantial respiratory morbidity, including unexplained lung disease orrecurrent pneumonia, and is an important issue in the rehabilitation unit. In particular,patientswithneurologicdiseasewhoareinalong-termbedriddenstatecanbeatgreaterriskfor development of chronic salivary aspiration and pulmonary complications [1,2].Incontrast to aspiration during the swallowing process, continuous secretion of saliva and itsaspiration are difficult to control, even through modification of food consistency orcessation of oral feeding.Useofaradionuclidesalivagramtodetectpassiveaspirationofsalivawasintroducedby Heyman [3] in 1989. After sublingual instillation of a small amount of radiolabeledcolloid, serial images are evaluated for the presence of radiotracer uptake in thetracheobronchial tree, which is suggestive of aspiration. This test may be useful fordetection of aspiration of saliva and for patients with limitations of oral feeding or poorcooperation. For these reasons, a radionuclide salivagram has been used in infants orchildren with neurologic diseases, for example, cerebral palsy, who have recurrentpulmonary infection [4-6]. A radionuclide salivagram can be performed under morephysiological conditions without the challenge of an oral bolus for swallowing and isless invasive than a videofluoroscopic swallow study or a fiberoptic-endoscopic evalu-ation of swallowing[4].TherehasbeenanincreaseintheuseofbotulinumneurotoxinA(BoNT-A)injectionintosalivary glands for the treatment of drooling in patients with neurologic disease, includingcerebral palsy [7], Parkinson disease [8], and amyotrophic lateral sclerosis [9,10]. Variousobjective or subjective methods have been used to evaluate treatment response to BoNT-Ainjection.However,mostofthemethodsfocusonreductionofsialorrheaordroolingitself.FewstudiesassesspulmonaryaspirationofsalivaaftersalivaryglandinjectionwithBoNT-A[11]. We hypothesized that a positive radionuclide salivagram could be strong evidence ofaspirationofsalivaandhelpfultoassesstheindicationformoreintensivetreatment,suchasglandinjectionwithbotulinumtoxinorsurgicalexcision.Inourexperiencewith2patients,saliva aspiration resolved after administration of BoNT-A into salivary glands, as demon-strated on a follow-up radionuclide salivagram.

Gabapentin effect on neuropathic pain compared among patients with spinal cord injury and different durations of symptoms. Point of View

Study Design. This study evaluated the effect of gaba-pentin on neuropathic pain in patients with spinal cord injury. Objective. To compare the effect of gabapentin on neuropathic pain refractory to conventional analgesics in patients with spinal cord injury and different durations of symptoms. of Background Data. Neuropathic pain in patients with spinal cord injury severely compromises their quality of life. Gabapentin is a new antieplleptic drug that may additionally have a role in the treatment of neuropathic pain. So far, there has been little prospective research investigating the effect of gabapentin on neuropathic pain in patients after spinal cord injury or comparing gabapentin-treated patients with varying durations of symptoms after spinal cord injury. Methods. The study included 31 patients who had experienced neuropathic pain associated with spinal cord injury or cauda equina syndrome. These subjects were divided into two groups. Group 1 (n = 13) was composed of patients whose duration of pain was less than 6 months, and Group 2 (n 18) comprised patients whose symptoms of neuropathic pain had lasted more than 6 months. Although these patients had been treated with conventional analgesics such as antidepressants, anticonvuisants, membrane stabilizer, and neuroleptics, they reported that their condition did not improve after a medication trial of at least 2 weeks duration. in this study, conventional analgesics were continued at a therapeutic level, and gabapentin was administrated for an 18-day titration period followed by a 5-week maintenance period at a dosage of 1800 mg/day or the maximum tolerable dosage. The efficacy of gabapentin administration was gauged by a pain score and a sleep interference score using a 100-mm visual analogue scale (VAS) every 2 weeks. The scores of the two groups were compared every 2 weeks over the course of the 8-week study. Results. The mean pain score and the mean sleep interference score for Group 1 decreased more than that of Group 2 during the interval between 2 to 8 weeks (P < 0.05). The mean pain score for Group 1 decreased from 7.3 ± 0.5 initially to 3 ± 0.6 after 8 weeks of treatment, whereas the corresponding score for Group 2 decreased from 7.6 ± 0.4 to 5.1 ± 0.6 (P < 0.05). The mean sleep interference score for Group 1 decreased from 5.7 ± 0.9 initially to 1.8 ± 0.8 after 8 weeks of treatment, whereas the corresponding score for Group 2 decreased from 5.9 ± 0.8 to 4.2 ± 0.7 (P < 0.05). As compared with the onset of this study, a decrease in pain score of 2 or more was reported at the completion of this study for 11 patients (100%) in Group 1 and 10 (71%) of 14 patients in Group 2. A decrease of 2 or more in sleep interference scores was reported for 8 (89%) of 9 patients with sleep interference in Group 1 and for 8 (62%) of 13 patients with sleep interference in Group 2. Some adverse effects such as somnolence were noted, but they were mild or moderate in intensity. Conclusions. Gabapentin may be effective in decreasing neuropathic pain refractory to conventional analgesics in some patients with spinal cord injury whose duration of symptoms is less than 6 months, although those with duration of symptoms longer than 6 months showed a significant decrease as well. The drug is unlikely to cause serious adverse effects that limit its use in patients with sninal cord iniury.

Effectiveness of Intra‐Articular Steroid Injection for Atlanto‐Occipital Joint Pain

OBJECTIVES The aims of this study were to evaluate the role of intra-articular joint injection for atlanto-occipital (AO) joint pain and to determine pain referral sites from that joint. DESIGN Prospective observational study. METHOD We evaluated 29 patients with chronic refractory neck pain and/or headache, and limited range of lateral bending with rotation at the AO joint on physical examination. Of the 24 patients who consented to undergo diagnostic injections, 20 patients had at least 50% relief from pain and underwent two AO intra-articular injections of mixture of local anesthetic and steroid approximately 1 week apart. Patients completed pain drawings, visual analog scales (VASs) for pain, and neck disability index (NDI) for level of function. Patients were evaluated for 2 months after the first injection. RESULT There was headache in 14/20 (70%), posterior neck pain (PNP) in 20, and referred pain in 17 (85%). The average VAS values for headache, PNP, and other referred pains were reduced significantly from 5.64, 5.70, and 5.41, respectively, before treatments to 0.64, 2.30, and 1.71, respectively, two months after injection (P < 0.01). The average NDI value was reduced significantly from 39.95% at pretreatment to 20.40% at 2 months after treatment (P < 0.01). CONCLUSION AO intra-articular steroid injection appears effective for the short-term control of chronic refractory pain arising from the AO joint.