- Email: [email protected]
38 WORKSHOP SUMMARY: RECENT DEVELOPMENTS IN POST HERPETIC NEURALGIA
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Oral presentations / European Journal of Pain Supplements 4 (2010) 1–46
36 OVERVIEW OF CURRENT AND EMERGING DRUG TREATMENTS FOR NEUROPATHIC PAIN AND RECOMMENDATIONS FOR USE N. Attal. Centre d’Evaluation et de Traitement de la Douleur, INSERM U 987 and APHP, Boulogne Billancourt, France Neuropathic pain remains extremely challenging to treat. A number of studies has confirmed the efficacy of tricyclic antidepressants, gabapentin, pregabalin, opioids, and tramadol for various neuropathic pain conditions and of selective serotonin noradrenaline reuptake inhibitors and topical lidocaine in painful neuropathies. Trials using combination therapy and comparative trials have recently appared, which has contributed to propose new evidence based therapeutic algorithms [1]. Emerging compounds include cannabinoids, topically applied capsaicin in high concentrations (8%), and botulinum toxin that have all been recently found effective in clinical trials. New molecular entities in clinical development including various glutamate antagonists, cytokine inhibitors, vanilloid-receptor antagonists, ion-channel blockers and neuronal nicotinic agonists. The challenge for future years will be better identify responder profiles to these drugs in order to reduce therapeutic failures. Reference(s) [1] N. Attal, G. Cruccu, R. Baron, M. Haanpa¨ a, ¨ P. Hansson, T.S. Jensen, T. Nurmikko EFNS guidelines on the pharmacological treatment of neuropathic pain: 2009; revision E J Neurol in press.
37 DEFINING RESPONDER PROFILES TO CURRENT AND EMERGING DRUG TREATMENT FOR NEUROPATHIC PAIN? R. Baron. Division of Neurological Pain Research and Therapy, Universit¨ atsklinikum Schleswig-Holstein, Kiel, Germany A new hypothetical concept was proposed in which pain is analyzed on the basis of underlying mechanisms rather than on the basis of the etiology. If a precise phenotypic characterization is combined with a selection of drugs acting at those particular mechanisms, it should ultimately be possible to design optimal treatments for the individual patient. Such research can only be performed in large cohorts of patients, ideally on a Research Network level. The German Research Network on Neuropathic Pain established a large data-base that includes epidemiological, clinical and history data as well as a standardized quantitative sensory testing (QST). Up to now more than 2000 patients with different neuropathic pain states have been examined. Furthermore, epidemiological and clinical data on the symptomatology of 2100 patients with painful diabetic neuropathy (DPN) and postherpetic neuralgia (PHN) from a cross sectional survey (painDETECT) are available. In several entities such as postherpetic neuralgia and painful diabetic neuropathy different sensory profiles could be analyzed which occur in different frequencies. The second step to be solved is the question whether an individual somatosensory phenotype really mirrors distinct pain mechanisms? For this purpose the technique of somatosensory pattern recognition was used and first results have been achieved. This approach uses the somatosensory patterns that are specific for human surrogate models of pain in which the underlying mechanisms are relatively well understood. The last and decisive question is whether these different phenotypes (which are presumably related to different mechanisms) are really associated with different treatment outcomes. In patients with focal neuropathic pain the somatosensory patterns were compared with the response to cutaneous lidocaine treatment. The patterns did not predict the response. Another study analyzed the response of neuropathic pain patients to systemic opioids. In this study the integrity of primary afferent nociceptors clearly correlated with a positive response to opioids. The results of such multi-center network trials will ultimately substantiate the mechanism based treatment concept in neuropathic pain.
Reference(s) Baron R, et al. A cross sectional cohort survey in 2100 patients with painful diabetic neuropathy and postherpetic neuralgia: Differences in demographic data and sensory symptoms. Pain 2009;146: 34–40. Rolke R, et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): Standardized protocol and reference values. Pain 2006;123: 231–43.
C3. Recent Developments in Post Herpetic Neuralgia 38 WORKSHOP SUMMARY: RECENT DEVELOPMENTS IN POST HERPETIC NEURALGIA A. Rice. Anaesthetics, Pain Medicine and Intensive Care, Imperial College London, London, UK • Chair & speaker 1: Andrew Rice (London, United Kingdom) • Speaker 2: Robert Dworkin (Rochester, USA) • Speaker 3: Maija Haanpaa (Helsinki, Finland) Herpes zoster and postherpetic neuralgia (PHN) are not only important in the context of neuropathic pain, but are also diseases that are predicted to expand in terms of global significance with the increased prevalence of herpes zoster as a result of an ageing developed world population, the world-wide pandemic of HIV disease and the increasing number of people receiving organ transplants. We are currently witnessing major and exciting developments, from several quarters, in our understanding of the mechanisms, prevention and treatment of herpes zoster and PHN. The workshop will focus on three of these: Participants will learn about: 1. Recent developments in attempting to model aspects of zoster associated pain in experimental animals. The use of complex behavioral paradigms to measure co-morbidities such as anxiety in these models (Rice). 2. Approaches for the prevention of both herpes zoster and PHN and their potential impact on the prevalence of these conditions. (Dworkin) 3. Appropriate clinical management strategies for the treatment of PHN based upon a systematic review of the available evidence, with a particular focus on the problems of prescribing in elderly patients (Haanpaa). 4. There will be 30 minutes for discussion. 39 MODELING VARICELLA ZOSTER-ASSOCIATED PAIN A. Rice. Anaesthetics, Pain Medicine and Intensive Care, Imperial College London, London, UK Because varicella zoster virus (VZV) is not a primary pathogen in rodents, it was thought for many years that it would not be possible to reproduce aspects of human VZV infection in rodents. However, it is now known that VZV in fact does become resident in the dorsal root ganglia cells of infected rats. This infection is associated with the development of pain-like behaviors and other features of neuropathic pain. Inoculation of rats with VZV is associated with the appearance of markers of VZV infection in dorsal root ganglion cells and a viral “dose” dependant, and persistent, hypersensitivity of limb withdrawal to static and dynamic mechanical stimuli. This hypersensitivity is reversible by drugs which are clinically effective in postherpetic neuralgia (PHN) (e.g. gabapentin, amitriptyline and morphine), but not by antiviral drugs, implying that active viral replication is not required for this behavioral response. Furthermore, VZV infected animals display a pharmacologicallysensitive fear/anxiety-like behavior (thigmotaxis), which perhaps reflects the anxiety reported by a significant proportion of patients with PHN and/or spontaneous pain. Analysis of biochemical markers of neuropathy has demonstrated some similarities to other
Oral presentations / European Journal of Pain Supplements 4 (2010) 1–46
36 OVERVIEW OF CURRENT AND EMERGING DRUG TREATMENTS FOR NEUROPATHIC PAIN AND RECOMMENDATIONS FOR USE N. Attal. Centre d’Evaluation et de Traitement de la Douleur, INSERM U 987 and APHP, Boulogne Billancourt, France Neuropathic pain remains extremely challenging to treat. A number of studies has confirmed the efficacy of tricyclic antidepressants, gabapentin, pregabalin, opioids, and tramadol for various neuropathic pain conditions and of selective serotonin noradrenaline reuptake inhibitors and topical lidocaine in painful neuropathies. Trials using combination therapy and comparative trials have recently appared, which has contributed to propose new evidence based therapeutic algorithms [1]. Emerging compounds include cannabinoids, topically applied capsaicin in high concentrations (8%), and botulinum toxin that have all been recently found effective in clinical trials. New molecular entities in clinical development including various glutamate antagonists, cytokine inhibitors, vanilloid-receptor antagonists, ion-channel blockers and neuronal nicotinic agonists. The challenge for future years will be better identify responder profiles to these drugs in order to reduce therapeutic failures. Reference(s) [1] N. Attal, G. Cruccu, R. Baron, M. Haanpa¨ a, ¨ P. Hansson, T.S. Jensen, T. Nurmikko EFNS guidelines on the pharmacological treatment of neuropathic pain: 2009; revision E J Neurol in press.
37 DEFINING RESPONDER PROFILES TO CURRENT AND EMERGING DRUG TREATMENT FOR NEUROPATHIC PAIN? R. Baron. Division of Neurological Pain Research and Therapy, Universit¨ atsklinikum Schleswig-Holstein, Kiel, Germany A new hypothetical concept was proposed in which pain is analyzed on the basis of underlying mechanisms rather than on the basis of the etiology. If a precise phenotypic characterization is combined with a selection of drugs acting at those particular mechanisms, it should ultimately be possible to design optimal treatments for the individual patient. Such research can only be performed in large cohorts of patients, ideally on a Research Network level. The German Research Network on Neuropathic Pain established a large data-base that includes epidemiological, clinical and history data as well as a standardized quantitative sensory testing (QST). Up to now more than 2000 patients with different neuropathic pain states have been examined. Furthermore, epidemiological and clinical data on the symptomatology of 2100 patients with painful diabetic neuropathy (DPN) and postherpetic neuralgia (PHN) from a cross sectional survey (painDETECT) are available. In several entities such as postherpetic neuralgia and painful diabetic neuropathy different sensory profiles could be analyzed which occur in different frequencies. The second step to be solved is the question whether an individual somatosensory phenotype really mirrors distinct pain mechanisms? For this purpose the technique of somatosensory pattern recognition was used and first results have been achieved. This approach uses the somatosensory patterns that are specific for human surrogate models of pain in which the underlying mechanisms are relatively well understood. The last and decisive question is whether these different phenotypes (which are presumably related to different mechanisms) are really associated with different treatment outcomes. In patients with focal neuropathic pain the somatosensory patterns were compared with the response to cutaneous lidocaine treatment. The patterns did not predict the response. Another study analyzed the response of neuropathic pain patients to systemic opioids. In this study the integrity of primary afferent nociceptors clearly correlated with a positive response to opioids. The results of such multi-center network trials will ultimately substantiate the mechanism based treatment concept in neuropathic pain.
Reference(s) Baron R, et al. A cross sectional cohort survey in 2100 patients with painful diabetic neuropathy and postherpetic neuralgia: Differences in demographic data and sensory symptoms. Pain 2009;146: 34–40. Rolke R, et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): Standardized protocol and reference values. Pain 2006;123: 231–43.
C3. Recent Developments in Post Herpetic Neuralgia 38 WORKSHOP SUMMARY: RECENT DEVELOPMENTS IN POST HERPETIC NEURALGIA A. Rice. Anaesthetics, Pain Medicine and Intensive Care, Imperial College London, London, UK • Chair & speaker 1: Andrew Rice (London, United Kingdom) • Speaker 2: Robert Dworkin (Rochester, USA) • Speaker 3: Maija Haanpaa (Helsinki, Finland) Herpes zoster and postherpetic neuralgia (PHN) are not only important in the context of neuropathic pain, but are also diseases that are predicted to expand in terms of global significance with the increased prevalence of herpes zoster as a result of an ageing developed world population, the world-wide pandemic of HIV disease and the increasing number of people receiving organ transplants. We are currently witnessing major and exciting developments, from several quarters, in our understanding of the mechanisms, prevention and treatment of herpes zoster and PHN. The workshop will focus on three of these: Participants will learn about: 1. Recent developments in attempting to model aspects of zoster associated pain in experimental animals. The use of complex behavioral paradigms to measure co-morbidities such as anxiety in these models (Rice). 2. Approaches for the prevention of both herpes zoster and PHN and their potential impact on the prevalence of these conditions. (Dworkin) 3. Appropriate clinical management strategies for the treatment of PHN based upon a systematic review of the available evidence, with a particular focus on the problems of prescribing in elderly patients (Haanpaa). 4. There will be 30 minutes for discussion. 39 MODELING VARICELLA ZOSTER-ASSOCIATED PAIN A. Rice. Anaesthetics, Pain Medicine and Intensive Care, Imperial College London, London, UK Because varicella zoster virus (VZV) is not a primary pathogen in rodents, it was thought for many years that it would not be possible to reproduce aspects of human VZV infection in rodents. However, it is now known that VZV in fact does become resident in the dorsal root ganglia cells of infected rats. This infection is associated with the development of pain-like behaviors and other features of neuropathic pain. Inoculation of rats with VZV is associated with the appearance of markers of VZV infection in dorsal root ganglion cells and a viral “dose” dependant, and persistent, hypersensitivity of limb withdrawal to static and dynamic mechanical stimuli. This hypersensitivity is reversible by drugs which are clinically effective in postherpetic neuralgia (PHN) (e.g. gabapentin, amitriptyline and morphine), but not by antiviral drugs, implying that active viral replication is not required for this behavioral response. Furthermore, VZV infected animals display a pharmacologicallysensitive fear/anxiety-like behavior (thigmotaxis), which perhaps reflects the anxiety reported by a significant proportion of patients with PHN and/or spontaneous pain. Analysis of biochemical markers of neuropathy has demonstrated some similarities to other