Management Of Chronic Neuropathic Pain Research Articles

Should Pregabalin Be Used in the Management of Chronic Neuropathic Pain in Adults? A Cochrane Review Summary With Commentary.

Should Pregabalin Be Used in the Management of Chronic Neuropathic Pain in Adults? A Cochrane Review Summary With Commentary.

A comparison of chronic pain with and without neuropathic characteristics in a Hong Kong Chinese population: An analysis of pain related outcomes and patient help seeking behaviour

ObjectiveIn Western countries, chronic pain patients with neuropathic characteristics have more intense pain, greater negative impact in quality of life and worse psychological well-being. The aim of this study was to compare the outcomes, impact, and health seeking behaviours in Chinese chronic pain patients with and without neuropathic characteristics in Hong Kong.MethodsRandom telephone survey was conducted on the general Hong Kong population, and based on the Nuprin Pain Report. Specific questions on chronic and neuropathic pain were included. Respondents with pain lasting three months or more were asked to indicate their two most painful sites. Chi-square and Mann-Whitney U-test were used to investigate differences between variables in patients with and without neuropathic characteristics. P<0.05 was regarded as significant.ResultsThe response rate was 32.3%. Chronic pain patients with neuropathic characteristics reported higher pain scores and longer duration of pain (p = 0.0001). They reported greater negative impact on work and effect on daily life (p = 0.0131); were significantly more likely to consult pain specialists (p = 0.0006), Chinese medicine practitioners (p = 0.0203), and psychiatrists (p = 0.0212); and were significantly less likely to be prescribed oral analgesics (p = 0.0226), to feel ‘very satisfied’ (p = 0.0263) with prescribed treatment and to find oral analgesics ‘very useful’ (p = 0.0215). There was no difference in oral analgesic medications taken.ConclusionChinese individuals having chronic pain with neuropathic characteristics had worse pain related outcomes. Differences in help-seeking behaviour were observed. Lack of appropriate analgesic prescription suggests that identification and management of chronic neuropathic pain in Hong Kong needs to be improved.

Updated Guideline of the Canadian Pain Society for the pharmacological management of chronic neuropathic pain: Does it bring something new?

Updated Guideline of the Canadian Pain Society for the pharmacological management of chronic neuropathic pain: Does it bring something new?

Oral gabapentin premedication for post-tonsillectomy nausea, vomiting, and recovery

Background Gabapentin is a second-generation anticonvulsant that is successful in the management of chronic neuropathic pain. It was not previously known to be useful in acute perioperative conditions, but recently it has been used for acute perioperative conditions. However, evidence-based medicine suggests that perioperative administration is useful for postoperative analgesia, preoperative anxiolysis, attenuation of the hemodynamic response to laryngoscopy and intubation, and preventing chronic postsurgical pain, postoperative nausea and vomiting (PONV), and delirium. This article reviews the clinical trial data to describe the efficacy and safety of gabapentin for perioperative anesthetic management. Aim The aim of the study was to evaluate and update the effect of preoperative gabapentin on the incidence of postoperative vomiting and on analgesic requirements after adenotonsillectomy in pediatrics. Materials and methods This randomized, double-blind study was designed to explore the possible effects of oral gabapentin as a premedication on the incidence and severity of PONV and on the early recovery profile of pediatric patients undergoing adenotonsillectomy under sevoflurane anesthesia. Results The incidence of PONV in the gabapentin group was significantly lower than in the gabapentin group. However, the numbers of rescue ondansetron doses and the PONV severity score were comparable in the two groups. Conclusion The use of gabapentin as premedication in pediatric patients undergoing adenotonsillectomies under sevoflurane anesthesia reduces the incidence of PONV and emergence agitation in the early postoperative period. However, gabapentin did not reduce pain and analgesic consumption after surgery.

Management of chronic neuropathic pain with single and compounded topical analgesics.

The goal of our review was to emphasize important aspects that physicians should take into consideration when prescribing topical analgesics as part of chronic neuropathic pain treatment. We discuss the dermatopharmacokinetics and microstructural components of the skin, differences between topical and transdermal drug delivery, and topical medication effects on peripheral neuropathy and central sensitization. Even though the US FDA approved topical analgesics are 8%-capsaicin and 5%-lidocaine patches for treating postherpetic neuralgia, there are many other studies conducted on the efficacy of topical ketamine cream, clonidine gel, topical gabapentin, topical baclofen and topical phenytoin for peripheral neuropathic pain, either alone or in combination with other formulations. Furthermore, we discuss new compounded topical analgesics that are becoming more popular and that are showing promising results in the management of chronic peripheral neuropathies. However, more studies are needed for elucidation of the role of topical analgesics and their effects, especially when combined with other treatments.

Chronic neuropathic pain negatively associated with employment retention of cancer survivors: evidence from a national French survey.

Chronic neuropathic pain (CNP) is more prevalent among cancer survivors than among the general population. This study aims to investigate the role of CNP on job retention among cancer survivors, 5years after diagnosis. In 2015, 2009 individuals diagnosed with cancer in 2010 were interviewed in the French national survey VIe après le CANcer. Logistic regression investigated the relationship between CNP-measured using the seven-item Douleur Neuropathique 4 (DN4) questionnaire-and employment. Nine hundred sixty-nine individuals were aged 18-54 and employed at diagnosis and therefore were included. Eighty-two percent were still employed in 2015, 26% had fewer working hours than before diagnosis, and 55% had the same working hours. Thirty percent reported CNP 5years after diagnosis. These cancer survivors were less likely to be employed in 2015 than those without CNP and, if employed, were more likely to work fewer hours. After adjustment for gender, medical variables (adverse cancer event, prognosis, chemotherapy, and comorbidities) were found to still significantly affect employment retention in cancer survivors, as well as reporting CNP. Improving CNP screening and management is necessary to reduce its impact on cancer survivors' professional lives. Healthcare policy and medical cancer survivor's follow-up must take into account the importance of the substantial impact of CNP on cancer survivors' daily lives. Therefore, in order to ensure greater employment retention for cancer survivors, raising awareness of care providers about diagnosis and management of CNP is needed.

Una mirada actualizada del enfoque y tratamiento del dolor neuropático crónico en el paciente con lesión medular

Neuropathic pain associated with spinal cord injury is defined as a chronic pain secondary to an injury or disease affecting the somatosensory system; it is a frequent pathology of central origin which generates a negative impact on the quality of life, physical function, mood and rehabilitation.The approach and management of chronic neuropathic pain is a challenge for the physiatrist. Most patients have severe pain that is difficult to manage. The choice of pharmacological treatment according to the level of recommendation, interdisciplinary management, the use of adjunctive therapies and interventional management are important determinants of successful treatment.

Recent Advances in the Pharmacological Management of Neuropathic Pain

Chronic neuropathic pain (NeP) is common. Traditional pharmacological treatments can demonstrate surprisingly little efficacy for reducing pain scores or improving function, and their use is often limited by side effects. Research into chronic pain pathophysiology has expanded in recent years and only by understanding these underlying mechanisms will we be best placed to develop new and novel drug therapies. In this review article, we will highlight some of the more recent pharmacological agents that have established themselves in the pain physicians’ armamentarium and continue to gain popularity as the evidence base grows together with some of the supporting evidences for their use. It is anticipated that this article will act to bring to the forefront of the pain physicians’ mind some of the alternative therapies for the management of chronic NeP that are often thought of as tertiary- or even quaternary-line in many established guidelines.

Abstract PR314

Background & Objectives: Chronic non-malignant neuropathic pain management is a major challenge for the clinicians despite a wide range of analgesics and pain treatment protocols. First, second, and third line drug treatments for neuropathic pain include the use of anticonvulsants, tricyclic antidepressants, mixed serotonin and norepinephrine reuptake inhibitors, opioids and other various treatment opportunities. However, the results of these treatment protocols for neuropathic pain management are heterogeneous and sometimes with short term outcomes. Although nerve blocks have been recognized as a major modality in chronic pain management, they are not included in guidelines for chronic non-malignant neuropathic pain management. The aim of our study was to investigate whether administration of peripheral nerve blocks with local anesthetic and corticosteroid significantly reduced pain in patients with chronic non-malignant neuropathic pain resistant to standard treatment, based on guidelines for chronic neuropathic pain management. Materials & Methods: 55 patients with chronic non-malignant neuropathic pain that was resistant to standard treatment based on guidelines for neuropathic pain were included in our study. The mixture of local anesthetic (0.125% levobupivacaine) and corticosteroid (betamethasone) was used to perform the blocks of peripheral nerves. Pain was assessed by the use of numeric pain rating scale (NPRS), with range 0-10 (0-no pain to 10-worst possible pain). Pain was evaluated before the application of peripheral nerve blocks and 3 weeks after. Differences between groups of patients were assessed by Wilcoxon signed rank test. All P-values were two-sided and statistical significance (p) was set at a value of 0.01. Results: A Wilcoxon signed rank test revealed a statistically significant reduction in pain, assessed on NPRS, following administration of peripheral nerve blocks, z= –6.47, p< 0.01, with a large effect size (r= 0.62). The median score on NPRS decreased from pre-peripheral nerve block administration (Median= 9; interquartile range (8-10)) to post-peripheral nerve block administration (Median= 3; interquartile range (2-5)). Conclusion: Our results suggest that peripheral nerve blocks improve pain management in patients with chronic non-malignant neuropathic pain and that these interventions could be used as therapeutic approach for patients with neuropathic pain resistant to other treatment alternatives.

Psychological therapies for the management of chronic neuropathic pain in adults.

Neuropathic pain is thought to arise from damage to the somatosensory nervous system. Its prevalence is increasing in line with many chronic disorders such as diabetes. All treatments have limited effectiveness. Given the evidence regarding psychological treatment for distress and disability in people with various chronic pain conditions, we were interested to investigate whether psychological treatments have any effects for those with chronic neuropathic pain. To assess the effects of psychological treatments on pain experience, disability, mood, and health-care use in adults with chronic neuropathic pain. We searched for randomised controlled trials (RCTs) published in any language in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and PsycINFO, from database inception to March 2015. Full publications of RCTs on psychological interventions for neuropathic pain. Trials had to have lasted at least three months, had at least 20 participants in each arm at the end of treatment, and compared a psychological intervention with any active or inactive intervention. We used the standard methodological procedures expected by Cochrane. Two small studies (enrolling a total of 105 participants) met the inclusion criteria. One was a standard cognitive behavioural treatment (CBT) programme for 61 people with pain from spinal cord injury, followed up for three months, and compared with a waiting list. The other was weekly group psychotherapy for 44 people with burning mouth syndrome, compared with a daily placebo tablet. The overall risk of bias was high in both trials.The CBT study assessed participants for pain, disability, mood, and quality of life, with improvement in treatment and control groups. However, there was no more improvement in the treatment group than in the control for any outcome, either post-treatment or at follow-up. The group psychotherapy study only assessed pain, classifying participants by pain severity. There is a lack of evidence on the efficacy and safety of psychological interventions for people with neuropathic pain. There is insufficient evidence of the efficacy and safety of psychological interventions for chronic neuropathic pain. The two available studies show no benefit of treatment over either waiting list or placebo control groups.

Systemic administration of WY-14643, a selective synthetic agonist of peroxisome proliferator activator receptor-alpha, alters spinal neuronal firing in a rodent model of neuropathic pain

Background and aimsThe clinical management of chronic neuropathic pain remains a global health challenge. Current treatments are either ineffective, or associated with unwanted side-effects. The development of effective, safe therapies requires the identification of novel therapeutic targets using clinically relevant animal models of neuropathic pain.Peroxisome proliferator activated receptor alpha (PPARα), is a member of the nuclear hormone family of transcription factors, which is widely distributed in the peripheral and central nervous systems. Pharmacological studies report antinociceptive effects of PPARα agonists following systemic administration in rodent models of neuropathic pain, however the neuronal mechanisms and sites of action mediating these effects are unclear.The aim of this study was to investigate the effects of systemic administration of the synthetic PPARα agonist, WY-14643 on mechanically-evoked responses of spinal cord dorsal horn wide dynamic range (WDR) neurones in the spinal nerve ligated (SNL) model of neuropathic pain in rats. In addition, comparative molecular analysis of mRNA coding for PPARα and PPARα protein expression in the spinal cord of sham-operated and neuropathic rats was performed. MethodsLumbar L5–L6 spinal nerve ligation was performed in male Sprague–Dawley rats (110–130g) under isoflurane anaesthesia. Sham controls underwent similar surgical conditions, but without ligation of the L5–L6 spinal nerves. Hindpaw withdrawal thresholds were measured on the day of surgery -day 0, and on days- 2, 4, 7, 10 and 14 post-surgery. At day 14 extracellular single-unit recordings of spinal (WDR) dorsal horn neurons were performed in both sham and SNL neuropathic rats under anaesthesia. The effects of intraperitoneal (i.p.) administration of WY-14643 (15 and 30mg/kg) or vehicle on evoked responses of WDR neurons to punctate mechanical stimulation of the peripheral receptive field of varying bending force (8–60g) were recorded. In a separate cohort of SNL and sham neuropathic rats, the expression of mRNA coding for PPARα and protein expression in the ipsilateral and contralateral spinal cord was determined using quantitative real time polymerase chain reaction (qRT-PCR) and western blotting techniques respectively. ResultsWY-14643 (15 and 30mg/kg i.p.) rapidly attenuated mechanically evoked (8, 10 and 15g) responses of spinal WDR neurones in SNL, but not sham-operated rats. Molecular analysis revealed significantly increased PPARα protein, but not mRNA, expression in the ipsilateral spinal cord of SNL, compared to the contralateral side in SNL rats. There were no changes in PPARα mRNA or protein expression in the sham controls. ConclusionThe observation that levels of PPARα protein were increased in ipsilateral spinal cord of neuropathic rats supports a contribution of spinal sites of action mediating the effects of systemic WY-14643. Our data suggests that the inhibitory effects of a PPARα agonist on spinal neuronal responses may account, at least in part, for their analgesic effects of in neuropathic pain. ImplicationSelective activation of PPARα in the spinal cord may be therapeutically relevant for the treatment of neuropathic pain.

Long-Term Outcome of the Management of Chronic Neuropathic Pain: A Prospective Observational Study

This prospective observational cohort study addressed the long-term clinical effectiveness of the management of chronic neuropathic noncancer pain at 7 Canadian tertiary pain centers. Patients were treated according to standard guidelines and were followed at 3, 6, 12, 18, and 24 months. Standard outcome measures for pain, mood, quality of life, and overall treatment satisfaction were administered, with the primary outcome measure designated as the composite of 30% reduction in average pain intensity and 1-point decrease in the mean Interference Scale Score (0–10) of the Brief Pain Inventory at 12 months relative to baseline. Of 789 patients recruited, mean age was 53.5 ± 14.2 years (55% female) and mean duration of pain was 4.88 ± 5.82 years. Mean average pain intensity (0–10) at baseline was 6.1 ± 1.9. All standard outcome measures showed statistically significant improvement at 12 months relative to baseline (P < .001). However, only 23.7% attained clinically significant improvement in pain and function at 12 months as the primary outcome measure. Univariable analyses showed poorer outcomes at 12-month follow-up with longer duration of pain (P = .002), greater cigarette use (P = .01), more disability compensation (P = .001), and higher opioid doses at baseline and at 12 months (P < .02). Our present treatment modalities provide significant long-term benefit in only about a quarter of patients with neuropathic pain managed at tertiary care pain clinics. Opioid therapy may not be beneficial for the long term. PerspectiveEvidence-based treatment of chronic neuropathic pain provides long-term benefit in only about one-quarter of patients seen in tertiary care centers. Opioid therapy may not be beneficial.

Impact on health-related quality of life and costs of managing chronic neuropathic pain in academic pain centres: Results from a one-year prospective observational Canadian study.

The management of chronic pain, including neuropathic pain (NeP), is a major public health issue. However, there is a paucity of data evaluating pain management strategies in real-life settings. To inform policy makers about the economic value of managing chronic NeP in academic centres by conducting a subeconomic assessment of a Canadian multicentre cohort study aimed at determining the long-term outcomes of the management of chronic NeP in academic pain centres. Specific questions regarding the economic value of this type of program were answered by a subset of patients to provide further information to policy makers. Baseline demographic information and several pain-related measurements were collected at baseline, three, six and 12 months in the main study. A resource use questionnaire aimed at determining NeP-related costs and the EuroQoL-5 Dimension were collected in the subset study from consenting patients. Statistical analyses were conducted to compare outcomes over time and according to responder status. A total of 298 patients were evaluated in the present economic evaluation. The mean (± SD) age of the participants was 53.7±14.0 years, and 56% were female. At intake, the mean duration of NeP was >5 years. Statistically significant improvements in all pain and health-related quality of life outcomes were observed between the baseline and one-year visits. Use decreased over time for many health care resources (eg, visits to the emergency room decreased by one-half), which resulted in overall cost savings. The results suggest that increased access to academic pain centres should be facilitated in Canada.

Management of chronic neuropathic pain: a protocol for a multiple treatment comparison meta-analysis of randomised controlled trials

IntroductionChronic neuropathic pain is associated with reduced health-related quality of life and substantial socioeconomic costs. Current research addressing management of chronic neuropathic pain is limited. No review has evaluated all...

Gabapentin versus pregabalin in relieving early post-surgical neuropathic pain in patients after lumbar disc herniation surgery: a prospective clinical trial

Objectives:The roles of gabapentin and pregabalin are well established in the management of chronic neuropathic pain. Here, we investigated the effectiveness of pregabalin and gabapentin for treating acute neuropathic pain following lumbar discectomy.Methods:This prospective, non-randomized, and observational study included 54 patients who experienced acute neuropathic pain after lumbar discectomy. The assessments included the Leeds assessment of neuropathic symptoms and signs scale (LANSS), the Oswestry disability index (ODI), and the visual analog scale (VAS) pre-operatively and at 3 days, 6 months, and 1 year after surgery. The LANSS scores ≧12 suggest the presence of neuropathic pain. Those patients who reported neuropathic pain were randomly treated with gabapentin or pregabalin.Results:In the gabapentin group, the LANSS scores increased to 14 at 3 days after surgery. The patients improved neurologically and on the LANSS, which decreased to 10 points 6 months after surgery and to 4 points at 1 year (P < 0·001). In the pregabalin group, the LANSS scores increased from 12 to 16 points on post-operative day 3 and then decreased to 12 and 5 at the 6-month and 1-year follow-ups, respectively (both P < 0·001). The ODI and VAS scores significantly improved in both groups (P < 0·001).Discussion:Many patients may suffer from neuropathic pain in the early post-surgical period after lumbar discectomy. Gabapentin and pregabalin are anticonvulsant agents that may decrease perioperative central sensitization and early post-surgical neuropathic pain. Gabapentin and pregabalin effectively relieved neuropathic pain and prevented the conversion of acute pain to chronic pain at the 1-year follow-up after lumbar discectomy.

Management of chronic neuropathic pain of different causes with the combination of oral methadone along with ketamine

Management of chronic neuropathic pain of different causes with the combination of oral methadone along with ketamine

Targeting glutamate and opioid signaling by gene therapy in spinal cord injury-induced pain in rats

Low efficacy of current pharmacotherapy for chronic neuropathic pain demands search for novel therapeutic targets and approaches. Enhanced glutamate signaling through NMDA receptors is one of the hypothesized mechanisms underlying development of neuropathic pain. However, although effective in animal models, clinical use of NMDA antagonists is limited by adverse effects such as hallucinations and motor dysfunction. Opiates have also been used in treatment of chronic pain with various successes, mostly due to unwanted side effects. Previous studies in our lab have shown NMDA antagonists activity of serine-histogranin (SHG), a synthetic analog of naturally occurring histogranin, lacking adverse effect. Transplantation of recombinant rat neuronal progenitors transduced with SHG construct reduced hypersensitivity induced by peripheral nerve injury. In addition, SHG can enhance opioid antinociceptive potency, thus reducing opioid doses and attendant side effects. Endomorphins (EMs) are endogenous opioid peptides with high selectivity for μ-opioid receptors. The aim of this study was to evaluate the antinociceptive potency of combined gene therapy with hexSHG (a 6 copy multi-SHG construct) and EM1 genes in rats with neuropathic pain symptoms. Spinal cord clip compression was used to induce central neuropathic pain. Five weeks post injury, lenti-hexSHG recombinant cells or lenti–EM1 constructs were intraspinally injected. Reduction of tactile and cold allodynia was observed in both groups of rats and analgesic effects were attenuated by SHG antibody or naloxone respectively. To evaluate combined therapy, SHG peptide was intrathecally delivered to lenti-EM1 injected animals at 7 weeks post injury. This further reduced tactile and cold allodynia compared to EM1-only treated animals. Intraspinal injection of both lenti-plasmids together nearly completely abolished cold allodynia and modestly attenuated tactile allodynia. These results encourage us to engineer compound constructs encoding both SHG and EM1 peptides in order to achieve better long-term analgesic outcomes in management of chronic neuropathic pain. Supported by NS51667 and CNF 190926.

Chronic neuropathic pain management – a review article

Chronic neuropathic pain (NEP) is commonly seen in clinical practice and represents a challenge to patients as well as clinicians. Pain is a complex sensory modality, resulting from the physiological activation of nociceptors that trigger a behavioural process to protect the individual from any existing, or further, tissue damage. Conditions that are frequently associated with NEP can be classified into two main groups: first, conditions that cause damage to the central nervous system (CNS), such as cortical and subcortical strokes; and, secondly, conditions that cause damage to the peripheral nervous system (PNS) such as ischaemic neuropathy, nerve root compression and phantom pain. There are multiple theories and pathophysiological processes underlying NEP; both basic and human research indicates that a lesion of afferent pathways is necessary for development of NEP. Furthermore, data clearly indicate that several mechanisms can lead to NEP and many of these mechanisms do not depend on the cause of the disease. The main mechanisms for the development NEP are ectopic nerve activity, upregulation of receptor proteins, central sensitization, inflammatory mechanism and disinhibition. The management of chronic NEP is challenging and the primary goal is to treat the pain and associated comorbidities, such as anxiety and depression. The secondary goals of treatment are to improve sleep, the ability to function normally and the overall quality of life. Tricyclic antidepressants (TCAs) are the most effective treatment in the management of NEP; however, serotonin–noradrenaline reuptake inhibitors (SNRIs), gabapentin and pregabalin, or lidocaine patches are also effective. Randomized controlled trials have reported the efficacy of opioids for different peripheral and central neuropathic disorders; however, using opioids for the treatment of NEP is not necessarily associated with a significant improvement in quality of life, psychological comorbidities or sleep disorders. In summary, management of NEP should be tailored to the individual patient on the basis of pain type(s), the causative disease, the relevant psychological factors and the interactions between the biological and psychosocial processes.

Evidence-based pharmacological management of chronic neuropathic pain

Neuropathic pain (NP) is a chronic, debilitating symptomatology of lesions/injuries of the central and peripheral nervous system. As per pooled estimates, the prevalence is 7-8% in the general population; however, the prevalence varies with different neuropathic conditions. The aetiology can range from peripheral neuropathic conditions viz. peripheral diabetic neuropathic pain (PDNP), post-herpetic neuralgia (PHN), trigeminal neuralgia, HIV- associated polyneuropathy, cervical radiculopathy to central neuropathic conditions, viz. central post-stroke pain, spinal cord injury and the neuropathic pain associated with multiple sclerosis. Apart from the symptomatic perception of pain, neuropathic pain affects the cognitive and emotional aspects of the affected individual. The pain, being debilitating and resistant to over-the-counter analgesics, diminishes the quality of life, disrupts sleep and leads to psychiatric complications such as comorbid anxiety and depression. The management is palliative and involves drugs, psychological intervention, stimulations and nerve-blocking techniques. This review concentrates on the pharmacological therapeutic options available and focuses on the selection of the agent/s in accordance with the evidence. The first-line treatment includes the tricyclic antidepressants ([ TCAs]; amitriptyline, nortriptyline), selective serotonin norepinephrine inhibitors ([SNRIs]; duloxetine, venlafaxine), calcium channel alpha 2 - delta ligands (pregabalin, gabapentin), carbamazepine and oxcarbazepine. Lidocaine plasters are first-line options for specific focal conditions such as post-herpetic neuralgia. The second-line therapy includes the opioid analgesics and tramadol. The choice of drug selection should complement the patient’s age, type of neuropathic condition, tolerability to an agent, comorbid condition and cost-effectiveness. Management must be individualized with a realistic and composite goal of making the pain tolerable and improving the cognitive and emotional well-being.

Peripheral nerve injury produces a sustained shift in the balance between glutamate release and uptake in the dorsal horn of the spinal cord

Peripheral nerve injury provokes heightened excitability of primary sensory afferents including nociceptors, and elicits ectopic activity in lesioned and neighboring intact nerve fibers. The major transmitter released by sensory afferents in the superficial dorsal horn of the spinal cord is glutamate. Glutamate is critically involved in nociceptive signaling and the development of neuropathic pain. We recorded miniature excitatory postsynaptic currents (mEPSCs) from neurons in lamina II of the rat dorsal horn to assess spontaneous synaptic activity after spared nerve injury (SNI), a model of chronic neuropathic pain. Following SNI, the frequency of mEPSCs doubled, indicating heightened glutamate release from primary afferents or spinal interneurons. Consistent with this finding, glutamate concentrations in the cerebrospinal fluid were elevated at 1 and 4weeks after SNI. Transmitter uptake was insufficient to prevent the rise in extracellular glutamate as the expression of glutamate transporters remained unchanged or decreased. 2-Methyl-6-(phenylethynyl)pyridine hydrochloride, an antagonist of metabotropic glutamate receptor 5 (mGluR5), reduced the frequency of mEPSCs to its preinjury level, suggesting a positive feedback mechanism that involves facilitation of transmitter release by mGluR5 activation in the presence of high extracellular glutamate. Treatment with the β-lactam antibiotic ceftriaxone increased the expression of glutamate transporter 1 (Glt1) in the dorsal horn after SNI, raised transmitter uptake, and lowered extracellular glutamate. Improving glutamate clearance prevented the facilitation of transmitter release by mGluR5 and attenuated neuropathic pain-like behavior. Balancing glutamate release and uptake after nerve injury should be an important target in the management of chronic neuropathic pain.