Clinical Management Of Neuropathic Pain Research Articles

Future Treatment of Neuropathic Pain in Spinal Cord Injury: The Challenges of Nanomedicine, Supplements or Opportunities?

Neuropathic pain (NP) is a common chronic condition that severely affects patients with spinal cord injuries (SCI). It impairs the overall quality of life and is considered difficult to treat. Currently, clinical management of NP is often limited to drug therapy, primarily with opioid analgesics that have limited therapeutic efficacy. The persistence and intractability of NP following SCI and the potential health risks associated with opioids necessitate improved treatment approaches. Nanomedicine has gained increasing attention in recent years for its potential to improve therapeutic efficacy while minimizing toxicity by providing sensitive and targeted treatments that overcome the limitations of conventional pain medications. The current perspective begins with a brief discussion of the pathophysiological mechanisms underlying NP and the current pain treatment for SCI. We discuss the most frequently used nanomaterials in pain diagnosis and treatment as well as recent and ongoing efforts to effectively treat pain by proactively mediating pain signals following SCI. Although nanomedicine is a rapidly growing field, its application to NP in SCI is still limited. Therefore, additional work is required to improve the current treatment of NP following SCI.

Protein Tyrosine Phosphatase Receptor Type D Regulates Neuropathic Pain After Nerve Injury via the STING-IFN-I Pathway.

Neuropathic pain is usually caused by injury or dysfunction of the somatosensory system, and medicine is a common way of treatment. Currently, there are still no satisfactory drugs, like opioids and lidocaine, which carry a high risk of addiction. Protein tyrosine phosphatase receptor type D (PTPRD) is a known therapeutic target in addiction pathways and small molecule inhibitors targeting it, such as 7-butoxy illudalic acid analog (7-BIA), have recently been developed to tackle addition. PTPRD is also upregulated in the dorsal root ganglion (DRG) in a rat model of neuropathic pain, but is not yet clear whether PTPRD contributes to the development of neuropathic pain. Here, we established a chronic constriction injury (CCI) and evaluated PTPRD expression and its association with neuropathic pain. PTPRD expression was found to gradually increase after CCI in DRGs, and its expression was concomitant with the progressive development of hypersensitivity as assessed by both mechanical and thermal stimuli. Both PTPRD knockdown and administration of PTPRD inhibitor 7-BIA alleviated CCI-induced neuropathic pain while upregulating STING and IFN-α in the DRG. Treatment with H-151, a STING inhibitor, abolished the analgesic effects of PTPRD knockdown. Taken together, our study suggests that increased levels of PTPRD in the DRG following CCI are involved in the development of neuropathic pain via the STING-IFN-I pathway. 7-BIA, a small molecule inhibitor of PTPRD with anti-addiction effects, may represent a novel and safe therapeutic strategy for the clinical management of neuropathic pain without the risk of addiction.

Emerging roles of circular RNAs in neuropathic pain.

Neuropathic pain is a major type of chronic pain caused by the disease or injury of the somatosensory nervous system. It afflicts about 10% of the general population with a significant proportion of patients’ refractory to conventional medical treatment. This highlights the importance of a better understanding of the molecular pathogenesis of neuropathic pain so as to drive the development of novel mechanism‐driven therapy. Circular RNAs (circRNAs) are a type of non‐coding, regulatory RNAs that exhibit tissue‐ and disease‐specific expression. An increasing number of studies reported that circRNAs may play pivotal roles in the development of neuropathic pain. In this review, we first summarize circRNA expression profiling studies on neuropathic pain. We also highlight the molecular mechanisms of specific circRNAs (circHIPK3, circAnks1a, ciRS‐7, cZRANB1, circZNF609 and circ_0005075) that play key functional roles in the pathogenesis of neuropathic pain and discuss their potential diagnostic, prognostic, and therapeutic utilization in the clinical management of neuropathic pain.

AAAPT Diagnostic Criteria for Acute Neuropathic Pain.

Acute neuropathic pain is a significant diagnostic challenge, and it is closely related to our understanding of both acute pain and neuropathic pain. Diagnostic criteria for acute neuropathic pain should reflect our mechanistic understanding and provide a framework for research on and treatment of these complex pain conditions. The Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership with the U.S. Food and Drug Administration (FDA), the American Pain Society (APS), and the American Academy of Pain Medicine (AAPM) collaborated to develop the ACTTION-APS-AAPM Pain Taxonomy (AAAPT) for acute pain. A working group of experts in research and clinical management of neuropathic pain was convened. Group members used literature review and expert opinion to develop diagnostic criteria for acute neuropathic pain, as well as three specific examples of acute neuropathic pain conditions, using the five dimensions of the AAAPT classification of acute pain. AAAPT diagnostic criteria for acute neuropathic pain are presented. Application of these criteria to three specific conditions (pain related to herpes zoster, chemotherapy, and limb amputation) illustrates the spectrum of acute neuropathic pain and highlights unique features of each condition. The proposed AAAPT diagnostic criteria for acute neuropathic pain can be applied to various acute neuropathic pain conditions. Both the general and condition-specific criteria may guide future research, assessment, and management of acute neuropathic pain.

Bidirectional Action of Cenicriviroc, a CCR2/CCR5 Antagonist, Results in Alleviation of Pain-Related Behaviors and Potentiation of Opioid Analgesia in Rats With Peripheral Neuropathy

Clinical management of neuropathic pain is unsatisfactory, mainly due to its resistance to the effects of available analgesics, including opioids. Converging evidence indicates the functional interactions between chemokine and opioid receptors and their influence on nociceptive processes. Recent studies highlight that the CC chemokine receptors type 2 (CCR2) and 5 (CCR5) seem to be of particular interest. Therefore, in this study, we investigated the effects of the dual CCR2/CCR5 antagonist, cenicriviroc, on pain-related behaviors, neuroimmune processes, and the efficacy of opioids in rats after chronic constriction injury (CCI) of the sciatic nerve. To define the mechanisms of action of cenicriviroc, we studied changes in the activation/influx of glial and immune cells and, simultaneously, the expression level of CCR2, CCR5, and important pronociceptive cytokines in the spinal cord and dorsal root ganglia (DRG). We demonstrated that repeated intrathecal injections of cenicriviroc, in a dose-dependent manner, alleviated hypersensitivity to mechanical and thermal stimuli in rats after sciatic nerve injury, as measured by von Frey and cold plate tests. Behavioral effects were associated with the beneficial impact of cenicriviroc on the activation/influx level of C1q/IBA-1-positive cells in the spinal cord and/or DRG and GFAP-positive cells in DRG. In parallel, administration of cenicriviroc decreased the expression of CCR2 in the spinal cord and CCR5 in DRG. Concomitantly, we observed that the level of important pronociceptive factors (e.g., IL-1beta, IL-6, IL-18, and CCL3) were increased in the lumbar spinal cord and/or DRG 7 days following injury, and cenicriviroc was able to prevent these changes. Additionally, repeated administration of this dual CCR2/CCR5 antagonist enhanced the analgesic effects of morphine and buprenorphine in neuropathic rats, which can be associated with the ability of cenicriviroc to prevent nerve injury-induced downregulation of all opioid receptors at the DRG level. Overall, our results suggest that pharmacological modulation based on the simultaneous blockade of CCR2 and CCR5 may serve as an innovative strategy for the treatment of neuropathic pain, as well as in combination with opioids.

Troels Staehelin Jensen-dissecting pain.

Troels Staehelin Jensen-dissecting pain.

Gabapentin and NMDA receptor antagonists interacts synergistically to alleviate allodynia in two rat models of neuropathic pain.

Background and aims The clinical management of neuropathic pain remains a challenge. We examined the interaction between gabapentin and NMDA receptor antagonists dextromethrophan and MK-801 in alleviating neuropathic pain-like behaviors in rats after spinal cord or sciatic nerve injury. Methods Female and male rats were produced with Ischemic spinal cord injury and sciatic nerve injury. Gabapentin, dextromethorphan, MK-801 or drug combinations were injected with increasing doses. Mechanical response thresholds were tested with von Frey hairs to graded mechanical touch/pressure, and ethyl chloride spray was applied to assess the cold sensitivity before and after injuries. Results In spinally injured rats, gabapentin and dextromethorphan did not affect allodynia-like behaviors at doses of 30 and 20 mg/kg, respectively. In contrast, combination of 15 or 30 mg/kg gabapentin with dextromethorphan at 10 mg/kg produced total alleviation of allodynia to mechanical or cold stimulation. Further reducing the dose of gapapentin to 7.5 mg/kg and dextromethorphan to 5 mg/kg still produced significant effect. MK-801, another NMDA receptor antagonist, also enhanced the effect of gabapentin in spinally injured rats. Similar synergistic anti-allodynic effect between dextromethorphan and gabapentin was also observed in a rat model of partial sciatic nerve injury. No increased side effect was seen following the combination between gabapentin and dextromethorphan. Conclusions In conclusion, the present study suggested that combining NMDA receptor antagonists with gabapentin could provide synergistic effect to alleviate neuropathic pain and reduced side effects. Implications Combining NMDA receptor antagonists with gabapentin may provide a new approach in alleviating neuropathic pain with increased efficacy and reduced side effects.

Molecular Analysis of <i>Clerodendrum formicarum</i> Effects in Painful Diabetic Neuropathy in Rat

The pathophysiology of diabetic neuropathic pain is due to primarily metabolic and vascular fac- tors. There is an increase in sorbitol and fructose, glycated end products, reactive oxygen species and activation of protein kinase C in the diabetic state. All these factors lead to direct damage to the nerves. Taking effective clinical management of neuropathic pain is based on a pharmacologi- cal treatment that has shown their limits and many side effects. The hypothesis of central sensiti- zation inhibited by Clerodendrum formicarum, an African pharmacopoeia plant used to treat headaches, arthritis, epilepsy and chronic pain could act on astrocytes and microglial cells. The objective of this work is to study the effect of Clerodendrum formicarum (100, 150 and 200 mg/kg body weight) on astrocytes and microglial cells in a model of diabetic neuropathic pain induced by alloxan monohydrate (150 mg/kg). We noted a suppression of mechanical allodynia and me- chanical hyperalgesia respectively by the Von Frey filaments test and the pressure test on the paw by the Clerodendrum formicarum extracts (ECF) at different doses from 2 h at the first injection of the ECF. After 5 days of treatment, we expressed by Western Blot bands of different proteins and by quantitative RT-PCR, we determined inhibition of the expression of GFAP, CD11b and isoforms 1 and 2 of cyclooxygenase. These results suggest that ECF inhibits the activation of astrocytes, mi- croglial cells and cyclooxygenase signaling pathway.

Diabetic neuropathic pain: a role for testosterone metabolites

Diabetic neuropathy is associated with neuropathic pain in about 50% of diabetic subjects. Clinical management of neuropathic pain is complex and so far unsatisfactory. In this study, we analyzed the effects of the testosterone metabolites, dihydrotestosterone (DHT), and 3α-diol, on nociceptive and allodynia thresholds and on molecular and functional parameters related to pain modulation in the dorsal horns of the spinal cord and in the dorsal root ganglia of rats rendered diabetic by streptozotocin injection. Furthermore, the levels of DHT and 3α-diol were analyzed in the spinal cord. Diabetes resulted in a significant decrease in DHT levels in the spinal cord that was reverted by DHT or 3α-diol treatments. In addition, 3α-diol treatment resulted in a significant increase in 3α-diol in the spinal cord compared with control values. Both steroids showed analgesic properties on diabetic neuropathic pain, affecting different pain parameters and possibly by different mechanisms of action. Indeed, DHT counteracted the effect of diabetes on the mechanical nociceptive threshold, pre- and post-synaptic components, glutamate release, astrocyte immunoreactivity, and expression of interleukin-1β (IL1β), while 3α-diol was effective on tactile allodynia threshold, glutamate release, astrocyte immunoreactivity and the expression of substance P, toll-like receptor 4, tumor necrosis factor-α, transforming growth factor β-1, IL1β, and translocator protein. These results indicate that testosterone metabolites are potential agents for the treatment of diabetic neuropathic pain.

Neuropathic pain and neuromodulation techniques

Neuropathic pain is a common chronic intractable pain syndrome in clinical setting. It arises as a consequence of a lesion or disease affecting the somatosensory system /INS;[1] and may be associated with abnormal sensations called dysesthesia, pain produced by normally non-painful stimuli called allodynia and spontaneous pain. The mechanism of neuropathic pain remains /INS;unclear so far, and the management of patients with chronic neuropathic pain is challenging /INS;[2–/INS;6]. In this paper, I will discuss in brief the etiology, physiopathology and clinical management of neuropathic pain.

English

  There are many evidences which indicate that calcium channel related voltage plays an important role on the mechanism of neuropathic pain, but no strong evidence has been found yet on the role played by type-L calcium channel. The aim of this study was to evaluate this role in using a properly designed experiment. This cohort study was carried out on seven groups (eight  animals each) of male Wistar rats (200 to300 g). Chronic constriction nerve injury was performed on rats by loosely ligating their common sciatic nerve. The impact of corticosteron at 15 mg/kg on neuropathic pain behaviors was assessed in the presence or absence of verapamil as an L-VSC channel blocker at 5, 10 or 20 mg/kg. Standard procedures were employed to evaluate the behavioral pain responses including the thermal hyperalgesia and the thermal and mechanical allodynia. Our findings indicate that peripheral administration of corticosterone suppressed both hyperalgesia, and thermal and mechanical allodynia; however, verapamil pretreatment attenuated the effects of corticosterone on both thermal hyperalgesia and mechanical allodynia. In addition, the administration of verapamil alone at high dose (20 mg) suppressed both thermal and mechanical allodynia. These findings show that the inhibitory effects of glucocorticoids on neuropathic pain behaviors, at least in part, may be mediated through L-type VSC channels; but our findings suggest a potential role for glucocorticoids receptors agonists in combination with L-type VSC channels antagonists in the clinical management of neuropathic pain.   Key words: Corticosterone, L-type, calcium channel, mechanical allodynia, thermal allodynia, thermal hyperalgesia.

New Developments in the Treatment Algorithm for Peripheral Neuropathic Pain

Neuropathic pain often imposes a substantial and unrelenting burden on those individuals who have it; single-agent analgesics typically only reduce pain at best. Worldwide, five sets of treatment recommendations offer insight into managing neuropathic pain, including two European guidelines, one Canadian, one Latin American, and another constructed under the auspices of the International Association for the Study of Pain (IASP). The analgesics common to these guidelines are topical lidocaine, secondary amine tricyclic antidepressants, serotonin and norepinephrine dual reuptake inhibitors, calcium channel α(2)-δ ligands, tramadol, and opioid antagonists. Still, significant knowledge gaps in the treatment of neuropathic pain conditions have hampered the development of algorithms and multimodal approaches. As the evidence base expands, the addition of new comparative trial data will further refine the development of new guidance for clinical management of neuropathic pain. New alternatives for managing neuropathic pain, such as the high-concentration capsaicin patch, will enlarge the treatment armamentarium and potentially impact therapeutic guidelines.

HZ166, a novel GABA A receptor subtype-selective benzodiazepine site ligand, is antihyperalgesic in mouse models of inflammatory and neuropathic pain

Diminished GABAergic and glycinergic inhibition in the spinal dorsal horn contributes significantly to chronic pain of different origins. Accordingly, pharmacological facilitation of GABAergic inhibition by spinal benzodiazepines (BDZs) has been shown to reverse pathological pain in animals as well as in human patients. Previous studies in GABA A receptor point-mutated mice have demonstrated that the spinal anti-hyperalgesic effect of classical BDZs is mainly mediated by GABA A receptors containing the α2 subunit (α2-GABA A receptors), while α1-GABA A receptors, which mediate the sedative effects, do not contribute. Here, we investigated the potential analgesic profile of HZ166, a new partial BDZ-site agonist with preferential activity at α2- and α3-GABA A receptors. HZ166 showed a dose-dependent anti-hyperalgesic effect in mouse models of neuropathic and inflammatory pain, triggered by chronic constriction injury (CCI) of the sciatic nerve and by subcutaneous injection of the yeast extract zymosan A, respectively. This antihyperalgesic activity was antagonized by flumazenil and hence mediated via the BDZ-binding site of GABA A receptors. A central site of action of HZ166 was consistent with its pharmacokinetics in the CNS. When non-sedative doses of HZ166 and gabapentin, a drug widely used in the clinical management of neuropathic pain, were compared, the efficacies of both drugs against CCI-induced pain were similar. At doses producing already maximal antihyperalgesia, HZ166 was devoid of sedation and motor impairment, and showed no loss of analgesic activity during a 9-day chronic treatment period (i.e. no tolerance development). These findings provide further evidence that compounds selective for α2- and α3-GABA A receptors might constitute a novel class of analgesics suitable for the treatment of chronic pain.

Eficiencia de las consultas especializadas. A propósito del trabajo “Evaluación de la eficiencia del manejo clínico del dolor neuropático en consultas especializadas frente a consultas generales en unidades asistenciales de neurología en España”

With reference to the article “Assessment of the efficiency of the clinical management of neuropathic pain in specialist clinics compared to general clinics in neurology health care units in Spain” by Matias-Guiu et al, a reflection is made on the methodological and operational difficulties of working with results in health, quality of life or costs in something so subjective as pain, and its impact on daily life. It then highlights the importance of the decision to establish a specialist clinic or other type specific care team for neuropathic pain, adding another level of care. Some points are given for the analysis of that decision.

Is There a Place for β-Mimetics in Clinical Management of Neuropathic Pain? Salbutamol Therapy in Six Cases

Is There a Place for β-Mimetics in Clinical Management of Neuropathic Pain? Salbutamol Therapy in Six Cases

Assessment of the efficiency of the clinical management of neuropathic pain in specialist clinics compared to general clinics in neurology health care Units in Spain

Objectives To analyse the cost-consequences of chronic neuropathic pain (NP) outpatient care comparing management in general clinics (GC) versus specialised pain clinics (SPC) in neurology settings in Spain. Methods A 6-month retrospective, cross-sectional, comparative observational study including NeP subjects was designed. Sociodemographics and clinical characteristics of subjects along with pain-related healthcare and non-healthcare resource utilisation were recorded. Lost-work-days equivalent missed as a consequence of pain were also collected to compute indirect costs. Costs to society were calculated in euros for the year 2008. Severity and interference of pain were used for the main effectiveness evaluation. Results A total of 234 patients (53% in SPC), 56.8% women, aged 59.3±14.7 years, were included. Patients were allocated according to usual administrative procedures in each participant centre, consecutively and independently of the diagnosis and clinical status of patients. Yearly indirect costs were €1,299±2,804 in SPC compared to €1,483±3,452 in GC (p=0.660), while annual direct costs were, €2,911±3,335 and €3,563±4,797, respectively (p=0.239), with total costs of €4,210±4,654 and €5,060±6,250, respectively (p=0.249). Mean pain severity at the time of evaluation was 3.8±2.3 in subjects in SPC vs. 5.2±2 in GC (p<0.001), while the mean interference of pain on daily activities was 3.3±2 and 4.7±2.5, respectively (p<0.001). Conclusions In neurology settings in Spain, the outpatient clinical management of chronic NP in SPC is a dominant alternative compared with GC healthcare, since it has shown better patient healthcare outcomes with less severity and interference of pain on daily activities, while maintaining a similar level of costs. These results could help health decision makers when planning the use of healthcare resources.

Combining Ketamine with Astrocytic Inhibitor as a Potential Analgesic Strategy for Neuropathic Pain. Ketamine, Astrocytic Inhibitor and Pain

BackgroundNeuropathic pain is an intractable clinical problem. Intrathecal ketamine, a noncompetitive N--methyl-D-aspartate receptor (NMDAR) antagonist, is reported to be useful for treating neuropathic pain in clinic by inhibiting the activity of spinal neurons. Nevertheless, emerging studies have disclosed that spinal astrocytes played a critical role in the initiation and maintenance of neuropathic pain. However, the present clinical therapeutics is still just concerning about neuronal participation. Therefore, the present study is to validate the coadministration effects of a neuronal noncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine and astrocytic cytotoxin L-α-aminoadipate (LAA) on spinal nerve ligation (SNL)-induced neuropathic pain.ResultsIntrathecal ketamine (10, 100, 1000 μg/kg) or LAA (10, 50, 100 nmol) alleviated SNL-induced mechanical allodynia in a dose-dependent manner respectively. Phosphorylated NR1 (pNR1) or glial fibrillary acidic protein (GFAP) expression was down-regulated by intrathecal ketamine (100, 1000 μg/kg) or LAA (50, 100 nmol) respectively. The combination of ketamine (100 μg/kg) with LAA (50 nmol) showed superadditive effects on neuropathic pain compared with that of intrathecal administration of either ketamine or LAA alone. Combined administration obviously relieved mechanical allodynia in a quick and stable manner. Moreover, down-regulation of pNR1 and GFAP expression were also enhanced by drugs coadministration.ConclusionsThese results suggest that combining NMDAR antagonist ketamine with an astrocytic inhibitor or cytotoxin, which is suitable for clinical use once synthesized, might be a potential strategy for clinical management of neuropathic pain.

Acetazolamide and midazolam act synergistically to inhibit neuropathic pain

Treatment of neuropathic pain is a major clinical challenge that has been met with minimal success. After peripheral nerve injury, a decrease in the expression of the K–Cl cotransporter KCC2, a major neuronal Cl − extruder, leads to pathologic alterations in GABA A and glycine receptor function in the spinal cord. The down-regulation of KCC2 is expected to cause a reduction in Cl − extrusion capacity in dorsal horn neurons, which, together with the depolarizing efflux of HCO 3 - anions via GABA A channels, would result in a decrease in the efficacy of GABA A-mediated inhibition. Carbonic anhydrases (CA) facilitate intracellular HCO 3 - generation and hence, we hypothesized that inhibition of CAs would enhance the efficacy of GABAergic inhibition in the context of neuropathic pain. Despite the decrease in KCC2 expression, spinal administration of benzodiazepines has been shown to be anti-allodynic in neuropathic conditions. Thus, we also hypothesized that spinal inhibition of CAs might enhance the anti-allodynic effects of spinally administered benzodiazepines. Here, we show that inhibition of spinal CA activity with acetazolamide (ACT) reduces neuropathic allodynia. Moreover, we demonstrate that spinal co-administration of ACT and midazolam (MZL) act synergistically to reduce neuropathic allodynia after peripheral nerve injury. These findings indicate that the combined use of CA inhibitors and benzodiazepines may be effective in the clinical management of neuropathic pain in humans.

Intrathecal Injection of the ς1Receptor Antagonist BD1047 Blocks Both Mechanical Allodynia and Increases in Spinal NR1 Expression during the Induction Phase of Rodent Neuropathic Pain

Selective blockade of spinal sigma(1) receptors (Sig-1R) suppresses nociceptive behaviors in the mouse formalin test. The current study was designed to verify whether intrathecal Sig-1R antagonists can also suppress chronic neuropathic pain. Neuropathic pain was produced by chronic constriction injury (CCI) of the right sciatic nerve in rats. The Sig-1R antagonist BD1047 was administered intrathecally twice daily from postoperative days 0 to 5 (induction phase of neuropathic pain) or from days 15 to 20 (maintenance phase). Western blot and immunohistochemistry were performed to determine changes in Sig-1R expression and to examine the effect of BD1047 on N-methyl-D-aspartate receptor subunit 1 expression and phosphorylation in spinal cord dorsal horn from neuropathic rats. BD1047 administered on postoperative days 0-5 significantly attenuated CCI-induced mechanical allodynia, but not thermal hyperalgesia, and this suppression was blocked by intrathecal administration of the Sig-1R agonist PRE084. In contrast, BD1047 treatment during the maintenance phase of neuropathic pain had no effect on mechanical allodynia. Sig-1R expression significantly increased in the ipsilateral spinal cord dorsal horn from days 1 to 3 after CCI. Importantly, BD1047 (30 nmol) administered intrathecally during the induction, but not the maintenance phase, blocked the CCI-induced increase in N-methyl-D-aspartate receptor subunit 1 expression and phosphorylation. These results demonstrate that spinal Sig-1Rs play a critical role in both the induction of mechanical allodynia and the activation of spinal N-methyl-d-aspartate receptors in CCI rats and suggest a potential therapeutic role for the use of Sig-1R antagonists in the clinical management of neuropathic pain.

Emerging Strategies for the Treatment of Neuropathic Pain.

Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts. jmao@partners.orgEmerging Strategies for the Treatment of Neuropathic Pain. Edited by James N. Campbell, M.D., Allan I. Basaum, Ph.D., Andre Dray, Ph.D., Ronald Dubner, D.D.S., Robert H. Dworkin, Ph.D., and Christine N. Sang, M.D. Seattle, Washington, IASP Press, 2006. Pages: 514. Price: $80.00.For those of us who practice pain medicine, it is undeniably challenging to treat patients with neuropathic pain. Neuropathic pain is a unique pain condition characterized by its dynamic nature and diversity of clinical presentation. Since the late 1980s, several animal models of peripheral nerve injury have been introduced, and the preclinical research field has witnessed an explosion of knowledge regarding the neural and molecular mechanisms of neuropathic pain. Despite the intense effort from both basic science and clinical pain research, the mechanisms of neuropathic pain remain largely unclear, and few new treatment options have been proven to be beneficial for the clinical management of neuropathic pain.The overall challenge facing preclinical research and clinical management of neuropathic pain is the theme of this extremely informative book published by the IASP Press. The book is a fine product of a scientific meeting organized by the book editors. Each of these topics listed in the book, ranging from the neural/molecular and disease-specific targets of neuropathic pain interventions to pain measurement and new technologies, was debated and deliberated during the meeting. As a researcher and pain clinician who has been interested in neuropathic pain, I find this book to be highly refreshing, loaded with the most updated information from a list of who is who in the field of neuropathic pain research and clinical management.A unique feature of this book is the inclusion of several rapporteur reports serving as the lead chapter for each section. Each rapporteur report contains the consensus from the meeting attendants on a particular research area as well as the discussion process that led to the consensus. These rapporteur reports, four of which are in this book, provide the readers with a rare opportunity to understand the thinking process of these experts who have devoted their effort to studying the mechanisms of neuropathic pain. The contents of these rapporteur reports are well balanced, carefully organized, and clearly presented. Particularly, research questions are raised within these rapporteur reports, which are aimed at guiding future research efforts in this field.Over several years, there have been many talks regarding the lack of adequate progress in both preclinical and clinical research on neuropathic pain and its clinical management. This book provides a realistic look at the current status of neuropathic pain research and treatment as well as the challenges ahead of us. For this reason, I highly recommend this book to those who are interested in the research and/or clinical management of neuropathic pain.Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts. jmao@partners.org