Sphingosine-1-phosphate receptor 1 activation in astrocytes contributes to neuropathic pain.

Neuropathic pain afflicts millions of individuals and represents a major health problem for which there is limited effective and safe therapy. Emerging literature links altered sphingolipid metabolism to nociceptive processing. However, the neuropharmacology of sphingolipid signaling in the central nervous system in the context of chronic pain remains largely unexplored and controversial. We now provide evidence that sphingosine-1-phosphate (S1P) generated in the dorsal horn of the spinal cord in response to nerve injury drives neuropathic pain by selectively activating the S1P receptor subtype 1 (S1PR1) in astrocytes. Accordingly, genetic and pharmacological inhibition of S1PR1 with multiple antagonists in distinct chemical classes, but not agonists, attenuated and even reversed neuropathic pain in rodents of both sexes and in two models of traumatic nerve injury. These S1PR1 antagonists retained their ability to inhibit neuropathic pain during sustained drug administration, and their effects were independent of endogenous opioid circuits. Moreover, mice with astrocyte-specific knockout of S1pr1 did not develop neuropathic pain following nerve injury, thereby identifying astrocytes as the primary cellular substrate of S1PR1 activity. On a molecular level, the beneficial reductions in neuropathic pain resulting from S1PR1 inhibition were driven by interleukin 10 (IL-10), a potent neuroprotective and anti-inflammatory cytokine. Collectively, our results provide fundamental neurobiological insights that identify the cellular and molecular mechanisms engaged by the S1PR1 axis in neuropathic pain and establish S1PR1 as a target for therapeutic intervention with S1PR1 antagonists as a class of nonnarcotic analgesics.

Citrus Naringenin Increases Neuron Survival in Optic Nerve Crush Injury Model by Inhibiting JNK-JUN Pathway.

Traumatic nerve injury activates cell stress pathways, resulting in neuronal death and loss of vital neural functions. To date, there are no available neuroprotectants for the treatment of traumatic neural injuries. Here, we studied three important flavanones of citrus components, in vitro and in vivo, to reveal their roles in inhibiting the JNK (c-Jun N-terminal kinase)-JUN pathway and their neuroprotective effects in the optic nerve crush injury model, a kind of traumatic nerve injury in the central nervous system. Results showed that both neural injury in vivo and cell stress in vitro activated the JNK-JUN pathway and increased JUN phosphorylation. We also demonstrated that naringenin treatment completely inhibited stress-induced JUN phosphorylation in cultured cells, whereas nobiletin and hesperidin only partially inhibited JUN phosphorylation. Neuroprotection studies in optic nerve crush injury mouse models revealed that naringenin treatment increased the survival of retinal ganglion cells after traumatic optic nerve injury, while the other two components had no neuroprotective effect. The neuroprotection effect of naringenin was due to the inhibition of JUN phosphorylation in crush-injured retinal ganglion cells. Therefore, the citrus component naringenin provides neuroprotection through the inhibition of the JNK-JUN pathway by inhibiting JUN phosphorylation, indicating the potential application of citrus chemical components in the clinical therapy of traumatic optic nerve injuries.

Does granulocyte-colony stimulating factor stimulate peripheral nerve regeneration? An experimental study on traumatic lesion of the sciatic nerve in rats.

AIM OF THE STUDY: To analyse the therapeutic potential of granulocyte-colony stimulating factor (G-CSF) treatment using a rat model of traumatic sciatic nerve lesion. CLINICAL RATIONALE FOR THE STUDY: G-CSF has proven strong neurotrophic properties in various models of ischaemic and traumatic brain injury. Fewer studies exist regarding the influence of G-CSF on posttraumatic peripheral nerve regeneration. Currently, the possibilities of pharmacological prevention or treatment of mechanical nerve injury are limited, and there is an urgent need to find new treatment strategies applicable in clinical situations. MATERIAL AND METHODS: A controlled traumatic right sciatic nerve lesion was set using a waterjet device. Three treatment groups were created. In the first group, G-CSF was administered after sciatic nerve injury. The second group received G-CSF before and after trauma, while the third group was treated with glucose 5%-solution. Sciatic nerve function was assessed clinically and electrophysiologically at day 1, and after weeks 1, 2, 4 and 6. Additionally, α-motoneurons of the spinal cord and sciatic nerve fibres were counted at week 6. RESULTS: Clinically, rats in both G-CSF groups improved faster compared to the control group. Additionally, animals treated with G-CSF had a significantly better improvement of motor potential amplitude and motor nerve conduction velocity at week 6 (p < 0.05). Histologically, G-CSF treatment resulted in a significantly higher number of α-motoneurons and small myelinated nerve fibres compared to placebo treatment (p < 0.05). CONCLUSIONS AND CLINICAL IMPLICATIONS: Under G-CSF treatment, the recovery of motor nerve conduction velocity and amplitude was enhanced. Further, signs of nerve regeneration and preservation of α-motoneurons were observed. These results indicate that G-CSF might accelerate and intensify the recovery of injured nerves. Thus, treatment with G-CSF may be beneficial for patients with peripheral nerve damage, and should be explored in further clinical studies.

Examination of the human motor endplate after brachial plexus injury with two-photon microscopy.

INTRODUCTION: After traumatic nerve injury, neuromuscular junction remodeling plays a key role in determining functional outcomes. Immunohistochemical analyses of denervated muscle biopsies may provide valuable prognostic data regarding clinical outcomes to supplement electrodiagnostic studies. METHODS: We performed biopsies on nonfunctioning deltoid muscles in two patients after gunshot wounds and visualized the neuromuscular junctions using two-photon microscopy with immunohistochemistry. RESULTS: Although the nerves in both patients showed evidence of acute Wallerian degeneration, some of the motor endplates were intact but exhibited significantly decreased surface area and volume. Both patients exhibited substantial recovery of motor function over several weeks postinjury. DISCUSSION: Two-photon microscopic assessment of neuromuscular junction integrity and motor endplate morphometry in muscle biopsies provided evidence of partial sparing of muscle innervation. This finding supported the clinical judgment that eventual recovery would occur. With further study, this technique may help to guide operative decisionmaking after traumatic nerve injuries.

Musculocutaneous neuropathy.

INTRODUCTION: Isolated musculocutaneous neuropathy is uncommon. In this study we aimed to determine its causes and clinical presentation and interpret the electrodiagnostic findings associated with this condition. METHODS: Our investigation was a retrospective review of patients diagnosed with musculocutaneous neuropathy at the Mayo Clinic (Rochester, Minnesota) electromyography (EMG) laboratory between 1997 and 2015. RESULTS: Thirty-two patients with musculocutaneous neuropathy and 5 patients with lateral antebrachial cutaneous neuropathy were identified. The most common cause was acute trauma or surgery (65%). Fourteen percent of the cases were idiopathic and 14% were inflammatory. Pain and sensory disturbance were more common presentations than weakness. Weakness from nerve injury was not noted in 2 patients, suggesting that other muscles may provide adequate elbow flexion/supination. The bilateral absence of lateral antebrachial cutaneous nerve sensory responses suggests an inflammatory cause. DISCUSSION: Musculocutaneous neuropathy usually results from trauma or iatrogenic injury. Nerve conduction studies alone are insufficient to confirm neuropathy, and needle EMG examination should be a routine part of the diagnostic evaluation. Muscle Nerve 58: 726-729, 2018.

Hallmarks of peripheral nerve injury and regeneration.

Peripheral nerves are functional networks in the body. Disruption of these networks induces varied functional consequences depending on the types of nerves and organs affected. Despite the advances in microsurgical repair and understanding of nerve regeneration biology, restoring full functions after severe traumatic nerve injuries is still far from achieved. While a blunted growth response from axons and errors in axon guidance due to physical barriers may surface as the major hurdles in repairing nerves, critical additional cellular and molecular aspects challenge the orderly healing of injured nerves. Understanding the systematic reprogramming of injured nerves at the cellular and molecular levels, referred to here as "hallmarks of nerve injury regeneration," will offer better ideas. This chapter discusses the hallmarks of nerve injury and regeneration and critical points of failures in the natural healing process. Potential pharmacological and nonpharmacological intervention points for repairing nerves are also discussed.

Successful treatment of neurologic injury after complex spinal surgery with hyperbaric oxygen therapy: a case report.

Background: Neurologic injury is relatively common in the context of spinal surgery, and is often treated with physiotherapy, pharmacotherapy, or surgical intervention. Emerging evidence supports a possible role for hyperbaric oxygen therapy (HBOT) in the treatment of peripheral and spinal nerve injuries. We describe the successful use of HBOT in improving neurologic recovery after complex spine surgery with new-onset postoperative unilateral foot drop. Case Description: A 50-year-old woman was found to have new right-sided foot drop and L2-S1 motor deficits following complex thoracolumbar revision spinal surgery. She received standard conservative management for a provisional diagnosis of acute traumatic nerve ischemia, but demonstrated no neurologic improvement. On postoperative day four, after other avenues of treatment were exhausted, she was referred for HBOT. The patient received a total of twelve sessions of HBOT at 2.0 absolute atmospheres (ATA) of pressure, for 90 minutes (including two air breaks) per session, before transfer to a rehabilitation facility. Conclusions: The patient displayed marked neurologic improvement after the first hyperbaric session, and further recovery thereafter. She concluded therapy with a significantly improved range of motion and lower limb power, ability to ambulate, and pain control. HBOT was associated with a rapid, sustained improvement when applied in this case as a salvage therapy for persistent postoperative neurologic deficit. Mounting evidence supports the consideration of hyperbaric therapy as a standard adjunct treatment for traumatic neurologic injury.

Polyethylene Glycol Fusion of Nerve Injuries: Review of the Technique and Clinical Applicability.

Traumatic peripheral nerve injuries present a particular challenge to hand surgeons as mechanisms of nerve-healing pose serious limitations to achieving complete functional recovery. The loss of distal axonal segments through Wallerian degeneration results in the loss of neuromuscular junctions and irreversible muscle atrophy. Current methods of repair depend on the outgrowth of proximal nerve fibers following direct end-to-end repair or gap repair techniques. Investigational techniques in nerve repair using polyethylene glycol (PEG) nerve fusion have been shown to bypass Wallerian degeneration by immediately restoring nerve axonal continuity, thus resulting in a rapid and more complete functional recovery. The purpose of this article is to review the current literature surrounding this novel technique for traumatic nerve repair, paying particular attention to the underlying physiology of nerve healing and the current applications of PEG fusion in the laboratory and clinical setting. This article also serves to identify areas of future investigation to further establish validity and feasibility and encourage the translation of PEG fusion into clinical use.

Postendodontic pain: a practical approach to diagnosis and management.

OBJECTIVES: Endodontic treatment is a routine procedure performed by general dental practitioners and endodontists on a daily basis. Fortunately, most patients undergoing endodontic therapy show a favorable outcome with uneventful healing. However, some patients develop pain following endodontic therapy. A majority of these patients develop acute, nociceptive pain ("flare-up") that resolves with appropriate treatment and subsequent healing. The dental profession is very adept at successfully managing the acute pain that occurs early following endodontic treatment. A minority of patients, however, develop ongoing pain following root canal therapy, termed chronic if persisting for 3 months or more. The diagnosis and management of chronic postendodontic pain are often challenging. This article aims to review pain following endodontic therapy, ranging from acute to chronic pain and its management, with specific emphasis on chronic pain, its pathophysiology, clinical features, diagnostic criteria, and management modalities. CONCLUSION: Endodontic treatment rarely leads to chronic neuropathic pain; however, when the nerve injury occurs and results in posttraumatic trigeminal neuropathic pain (PTNP), treatment options are very limited and rarely successful. Therefore, all steps should be taken to avoid nerve injury. Prevention of endodontic treatment related PTNP is crucial and achieved through early recognition, and prompt management.

(4-Aminopyridine)-PLGA-PEG as a Novel Thermosensitive and Locally Injectable Treatment for Acute Peripheral Nerve Injury.

Traumatic peripheral nerve injury (TPNI) represents a major medical problem that results in loss of motor and sensory function, and in severe cases, limb paralysis and amputation. To date, there are no effective treatments beyond surgery in selective cases. In repurposing studies, we found that daily systemic administration of the FDA-approved drug 4-aminopyridine (4-AP) enhanced functional recovery after acute peripheral nerve injury. This study was aimed at constructing a novel local delivery system of 4-AP using thermogelling polymers. We optimized a thermosensitive (4-AP)-poly(lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(lactide-co-glycolide) (PLGA-PEG-PLGA) block copolymer formulation. (4-AP)-PLGA-PEG exhibited controlled release of 4-AP both in vitro and in vivo for approximately 3 weeks, with clinically relevant safe serum levels in animals. Rheological investigation showed that (4-AP)-PLGA-PEG underwent a solution to gel transition at 32 °C, a physiologically relevant temperature, allowing us to administer it to an injured limb while subsequently forming an in situ gel. A single local administration of (4-AP)-PLGA-PEG remarkably enhanced motor and sensory functional recovery on post-sciatic nerve crush injury days 1, 3, 7, 14, and 21. Moreover, immunohistochemical studies of injured nerves treated with (4-AP)-PLGA-PEG demonstrated an increased expression of neurofilament heavy chain (NF-H) and myelin protein zero (MPZ) proteins, two major markers of nerve regeneration. These findings demonstrate that (4-AP)-PLGA-PEG may be a promising long-acting local therapeutic agent in TPNI, for which no pharmacologic treatment exists.

Antiapoptotic Effect of Granulocyte-Colony Stimulating Factor After Peripheral Nerve Trauma.

BACKGROUND: Granulocyte-colony stimulating factor (G-CSF) has been observed to have direct protective effects on neurons after stroke in experimental models and in humans. In the present study, the antiapoptotic effects of G-CSF on spinal α-motoneurons after inducement of peripheral sciatic nerve lesions were evaluated in a rat model. METHODS: Of 48 rats, 24 were treated with G-CSF and 24 were treated with glucose 5% solution (control group). The spinal cord of 6 rats in each group were removed at days 1, 4, 7, and 14. The α-motoneurons of spinal cord section L4-L6 were counted and investigated for the expression of choline acetyltransferase (ChAT), G-CSF receptor (G-CSFR), and Bcl-2 and Bax proteins. Additionally, α-motoneuron fluorescence double staining was performed for ChAT/Bcl-2, ChAT/Bax, and ChAT/G-CSFR. RESULTS: Without G-CSF treatment, the number of ChAT-positive α-motoneurons on the lesion side was significantly decreased (P < 0.001). The number of α-motoneurons with Bcl-2 and G-CSFR positivity on the lesion side was significantly decreased (P < 0.05). In contrast, the number of α-motoneurons with Bax positivity was significantly greater (P < 0.05). After G-CSF treatment, the differences in the number of α-motoneurons on the 2 sides were not statistically significant. Fluorescence double staining of α-motoneurons was positive for ChAT/Bcl-2, ChAT/Bax, and ChAT/G-CSFR. CONCLUSION: The results indicated that G-CSF has neuroprotective properties in spinal α-motoneurons and contributes to antiapoptotic effects after peripheral nerve lesions. The relevance of G-CSF, its precise mode of action, and the effect of these findings in clinical situations remains to be elucidated and require examination in further studies.

Intraoperative Imaging in Traumatic Peripheral Nerve Lesions: Correlating Histologic Cross-Sections with High-Resolution Ultrasound.

BACKGROUND: Intraoperative ultrasound (US) has been used as a guide during surgery to better identify deep neuroanatomical structures. OBJECTIVE: To correlate histologic cross-sections from nerve samples taken at the time of surgery with axial, high-resolution US images at similar locations and validate this important tool for intraoperative guidance in nerve surgery. METHODS: Three subjects undergoing nerve repair procedures after traumatic nerve injuries were enrolled prospectively. US images captured at the time of surgery were later matched with gross anatomic cross-sections and fascicular anatomy compared across modalities. RESULTS: In cases 1 and 3, neuromatous tissue spanned the entire cross-section of the common peroneal and upper trunk of the brachial plexus, respectively. In case 2, only a portion of the sciatic nerve was involved with neuroma. Intraoperative US aided in differentiating normal peripheral nerve from neuroma in all 3 cases and helped minimize the disruption of healthy peripheral nerve tissue. CONCLUSION: Intraoperative US correlates well with anatomic sections removed at the time of surgery. The ability to noninvasively image the peripheral nerve along with compound nerve action potentials can greatly assist in determining the extent of neurolysis, resection, and grafting and is a useful adjunct for intraoperative decision-making. This report serves to highlight the role of US and validate its use in peripheral nerve surgery for trauma.

Humerus shaft fracture associated with traumatic radial nerve palsy: An international survey among orthopedic trauma surgeons from Latin America and Asia/Pacific.

PURPOSE: The purpose of this article is to explore the real-life practice of clinical management of humeral shaft fracture associated with traumatic radial nerve palsy among orthopedic trauma surgeons. METHODS: Two hundred seventy-nine orthopedic surgeons worldwide reviewed 10 real cases of a humeral shaft fracture associated with traumatic radial nerve palsy answering two questions: (1) What treatment would you choose/recommend: nonoperative or operative? (2) What are the reasons for your decision-making? The survey was developed in an online survey tool. All participants were active members from AOTrauma International. RESULTS: Two hundred sixty-six (95.3%) participants were from Latin America and Asia/Pacific. One hundred sixty-two participants (58.1%) had more than 10 years in practice and 178 (63.8%) of them did trauma as the main area of interest. One hundred fifty-one (54.1%) participants treated less than three humeral shaft fractures a month. Traumatic radial nerve palsy was the main reason (88.4%) for surgeons to recommend surgical treatment. Open reduction and internal fixation (ORIF) or percutaneous fixation of the fracture associated with acutely explore of radial nerve was the first option in 62.0% of the cases. A combination of morphology and level of the fracture and the presence of the radial nerve palsy was the most suggested reason to surgically treat the humerus fracture. The main isolated factor was the morphology of the fracture. CONCLUSION: Our survey highlight the tendency for a more aggressive management of any humeral shaft fracture associated with a traumatic radial nerve palsy, with surgeons preferring to use ORIF with acute exploration of the radial nerve. Nonsurgical management was the less chosen option among the 279 respondents. Fracture morphology, level of the fracture, and the presence of the radial nerve palsy were most influential for guiding their treatment.

Management and complications of traumatic peripheral nerve injuries.

This article provides an overview of the management of traumatic peripheral nerve injuries. It examines the basic pathophysiology of peripheral nerve injuries, along with the clinical presentation, diagnostic work-up, and treatment options and outcomes for the various classifications of traumatic peripheral nerve injuries.

Activation of the Wnt/ß-catenin signaling cascade after traumatic nerve injury.

Recent data have shown that preservation of the neuromuscular junction (NMJ) after traumatic nerve injury helps to improve functional recovery with surgical repair via matrix metalloproteinase-3 (MMP3) blockade. As such, we sought to explore additional pathways that may augment this response. Wnt3a has been shown to inhibit acetylcholine receptor (AChR) clustering via ß-catenin-dependent signaling in the development of the NMJ. Therefore, we hypothesized that Wnt3a and ß-catenin are associated with NMJ destabilization following traumatic denervation. A critical size nerve defect was created by excising a 10-mm segment of the sciatic nerve in mice. Denervated muscles were then harvested at multiple time points for immunofluorescence staining, quantitative real-time PCR, and western blot analysis for Wnt3a and ß-catenin levels. Moreover, a novel Wnt/ß-catenin transgenic reporter mouse line was utilized to support our hypothesis of Wnt activation after traumatic nerve injury. The expression of Wnt3a mRNA was significantly increased by 2 weeks post-injury and remained upregulated for 2 months. Additionally, ß-catenin was activated at 2 months post-injury relative to controls. Correspondingly, immunohistochemical analysis of denervated transgenic mouse line TCF/Lef:H2B-GFP muscles demonstrated that the number of GFP-positive cells was increased at the motor endplate band. These collective data support that post-synaptic AChRs destabilize after denervation by a process that involves the Wnt/ß-catenin pathway. As such, this pathway serves as a potential therapeutic target to prevent the motor endplate degeneration that occurs following traumatic nerve injury.

Pregabalin in post traumatic neuropathic pain: Case studies.

Pregabalin is effective in the treatment of peripheral and central neuropathic pain. This study evaluated the effectiveness of pregablin in management of post traumatic peripheral nerve injury facial pain not responding to other medication like analgesics. Pregabalin was well tolerated. The most common adverse effects were dizziness and tiredness.

Transferencia tendinosa de tibial posterior en parálisis del nervio peróneo común: ¿El fin del pie caído? / Tendinous transfer of posterior tibial in paralysis of the common peroneal nerve: The end of the fallen foot?

INTRODUCCIÓN: la lesión del nervio peróneo común es la más frecuente del miembro inferior, resultando en pie caído y marcha en steppage. La reconstrucción nerviosa tiene un resultado desfavorable en la mayoría de las series. Una alternativa terapéutica a dicha reconstrucción es la transferencia del tendón del músculo tibial posterior, cuyo objetivo es lograr la dorsiflexión activa del pie. El objetivo de este trabajo es analizar los resultados obtenidos con esta cirugía. MATERIAL Y MÉTODOS: se analizaron una serie de pacientes a los que se realizó una transferencia de tendón de tibial posterior por pie caído, entre los meses de enero 2008 y junio 2012. Sólo se incluyeron en el análisis aquellos que presentaban un seguimiento de al menos 12 meses. La técnica empleada en todos los procedimientos fue la vía subcutánea, circunferencial, con fijación tendón-tendón, y usando como blanco los tendones del tibial anterior, extensor propio del hallux, extensor común de los dedos y peróneos laterales. La escala de Stanmore fue empleada para analizar los resultados. RESULTADOS: en el período analizado, fueron realizadas 22 transferencias de tibial posterior, de los cuales 19 poseían un seguimiento adecuado. Diez de esos 19 pacientes mostraron un resultado excelente (52,3%), cinco bueno (26,7%), dos pacientes regular (10,5%) y dos malo (10,5 %), de acuerdo a la escala mencionada. Sólo una complicación se verificó en un caso, la pérdida de tensión de la sutura tendinosa, que requirió una nueva cirugía. CONCLUSIÓN: la transferencia tendinosa de tibial posterior es un procedimiento con una alta tasa de éxito, tanto es nuestra serie como en otras publicadas en la literatura. Atento a los resultados generalmente pobres que posee la reconstrucción nerviosa primaria directa, consideramos que en casos seleccionados la técnica de transferencia tendinosa es la primera elección en el pie caído

INTRODUCTION: common peroneal nerve injury is the most frequent nerve deficit affecting the lower limbs, resulting in foot drop and stepagge. Primary surgical nerve repair has an unfavorable outcome in most series. An alternative is posterior tibial tendon transfer, a procedure designed to achieve active dorsiflexion. The aim of this paper is to analyze the results obtained with this surgery. METHODS: between January 2008 and June 2012, all patients submitted for posterior tibial tendon transfer with a minimum follow-up of 12 months, were analyzed. Subcutaneous route was used for the transfer, and tendon-to-tendon suture was employed, using as targets the anterior tibial, extensor hallucis longus, extensor digitorum longus and peroneal tendons. Stanmore scale was used for analysis. RESULTS: a total of 22 patients were operated in the studied period, but 19 who had a minimum follow-up were included in these analysis. The results were excellent in 10 patients (52,3%), good in 5 (26,7%), fair in in 2 patients (10,5%) and poor in 2 (10,5%), according to Stanmore scale. CONCLUSIONS: this tendon transfer has a high rate of success, both in our series and in the literature. Considering the poor results that primary nerve repairs has, we believe that posterior tibial tendon transfer is the first choice for the treatment of foot drop in selected cases

The Effect of Gabapentin for the Clinical Symptoms in the Traumatic Neuropathic Pain / 영남의대학술지

BACKGROUND: Gabapentin is widely used for the relief of neuropathic pain. But, there is no study of gabapentin in relation to traumatic neuropathic pain. The aim of this study is to assess the efficacy and effectiveness of gabapentin for the various clinical symptoms of traumatic neuropathic pain MATERIALS AND METHODS: 50 patients with traumatic nerve injury were assigned to receive gabapentin, titrated to 900 mg/day over 9 days, followed by further increases to a maximum of 2400 mg/day. Continuous pain, paroxysmal pain, allodynia and thermal evoked pain were measured in mean daily pain scores, based on the 11-point Likert scale. The primary efficacy parameter was compared from the baseline to the final study week. RESULTS: Over the 4.5 week study, this pain score decreased by 2.6 points in the continuous pain, 3.6 points in the paroxysmal pain, 3.1 points in the allodynia, and 2.5 points in the thermal evoked pain. The percentage of patients with over 50% improvement in pain scores was 33% in the continuous pain, 67% in the paroxysmal pain, 53% in the allodynia and 36% in the thermal evoked pain. There was no significant correlation between the effect of gabapentin and the time difference of the onset of symptoms and start of medication. CONCLUSIONS: This study shows that gabapentin reduced neuropathic pain in patients with traumatic peripheral nerve injury. Among the various characteristics of neuropathic pain, the reduction of paroxysmal pain and allodynia was greatest.