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97 Workshop Summary: TOPICAL AND TRANSDERMAL TREATMENTS FOR NEUROPATHIC PAIN
Invited Presentations / Workshop – Therapy 4 / European Journal of Pain 11(S1) (2007) S1–S57
randomized to receive a single dose of investigational zoster vaccine or placebo. Subjects were actively followed for HZ with the aid of an interactive Automated Telephone Response System, and more than 95% of the enrolled subjects were successfully followed to the end of the Study. A HZ-specific assessment tool, the Zoster Brief Pain Inventory (ZBPI), was developed and validated to capture HZ pain and discomfort, including unpleasant sensations such as allodynia and pruritus not always characterized as pain by persons with HZ. Clinically significant PHN was defined as HZ-associated pain or discomfort rated as P3 (on a 0-to-10 scale) persisting or appearing more than 90 days after HZ rash onset. ZBPI worst pain scores <3 are not associated with significant decrements in quality of life or ability to carry out activities of daily living, and thus were not considered to represent clinically significant PHN. Zoster vaccine reduced the Incidence of clinically significant PHN by 66.5% (P < 0.001), and the reduction was identical in both age strata. The zoster vaccine was well tolerated, and it neither caused nor induced HZ [Oxman MN, et al. N Engl J Med 2005;352:2271–84]. Immunological assays at baseline confirmed a progressive loss of VZV-CMI with increasing age (P < 0.001), and no significant age-related change in titers of antibody to VZV (P = 0.75). At 6 weeks after vaccination, VZV immune responses in vaccine recipients were significantly increased over baseline (P < 0.001) and compared to responses in placebo recipients, and significant increases were sustained at 1, 2, and 3 years. VZV-CMI responses in the vaccine group were greater in subjects 60–69 years of age than in those P70 (P < 0.01). These age-related differences in VZVCMI were paralleled by age-related differences in the incidence and severity of PHN, and in the clinical efficacy of the zoster vaccine. These results will be discussed in relation to the neuropathology and mechanisms of PHN. doi:10.1016/j.ejpain.2007.03.109
96 INVASIVE TREATMENT OF HERPES ZOSTER AND POSTHERPETIC NEURALGIA A.J.M. van Wijck Pain Clinic, University Medical Center Utrecht, The Netherlands Several invasive treatments are used for the treatment of herpes zoster (HZ) postherpetic neuralgia (PHN). They include subcutaneous injections, peripheral nerve blocks, sympathetic blocks, epidural injections, intrathecal injections and spinal cord stimulation (Opstelten, 2004; Kumar, 2004). The intervention can be aimed at relieve of acute pain in HZ, prevention of PHN or treat-
S39
ment of PHN. The efficacy of invasive therapies for the treatment of acute pain has been established in several randomized controlled trials (RCTs). For prevention of PHN, results of 2 RCTs are conflicting. One trial that used an epidural catheter for multiple injections of bupivacaine and methylprednisolone showed a significant reduction of PHN (Pasqualucci, 2000). A second trial that used a single epidural injection with bupivacain and methylprednisolone showed no preventive effect on PHN (van Wijck, 2006). One trial showed reduction of pain in patients with PHN by intrathecal administration of methylprednisolone (Kotani, 2000). References Opstelten, W. et al. (2004). Interventions to prevent postherpetic neuralgia: cutaneous and percutaneous techniques. Pain, 107(3), 202–206. Kumar, V. et al. (2004). Neuraxial and sympathetic blocks in herpes zoster and postherpetic neuralgia: an appraisal of current evidence. Reg Anesth Pain Med, 29, 454–461. Pasqualucci, A. et al. (2000). Prevention of post-herpetic neuralgia: acyclovir and prednisolone versus epidural local anesthetic and methylprednisolone. Acta Anaesthesiol Scand, 44, 910–918. van Wijck, A. J. et al. (2006). The PINE study of epidural steroids and local anaesthetics to prevent postherpetic neuralgia: a randomised controlled trial. Lancet, 367, 219–224. Kotani, N. et al. (2000). Intrathecal Methylprednisolone for Intractable Postherpetic Neuralgia. N Engl J Med, 343, 1514–1519. doi:10.1016/j.ejpain.2007.03.110
Workshop – Therapy 4: TOPICAL AND TRANSDERMAL TREATMENTS FOR NEUROPATHIC PAIN
97 Workshop Summary: TOPICAL AND TRANSDERMAL TREATMENTS FOR NEUROPATHIC PAIN G. Gourlay Pain Management Unit, Flinders Medical Centre, Adelaide, Australia This Workshop will consider various topical and transdermal interventions for the treatment of a variety of neuropathic pain states. The focus will be clearly on treatment options as mechanistic and diagnostic issues will be covered in other Workshops at this Congress. The role of topical capsaicin in general, but particularly more recent information concerning high dose capsaicin patches will be presented by Dr. Backonja. In recent years cutaneous application of lignocaine via patches containing 5% lignocaine, has become a recommended treatment for neuropathic pain. Evidence, advantages and limitations of these topical treatment strategies will be presented by Dr. Wasner. Further, the possibility of predicting the efficacy of topical agents in
S40
Invited Presentations / Workshop – Therapy 4 / European Journal of Pain 11(S1) (2007) S1–S57
subgroups of patients will be discussed. Finally, Dr. Alon will consider the role of transdermal fentanyl and buprenorphine in the treatment of neuropathic pain. Evidence for the role of these interventions together with the strengths and limitations of each treatment modality in reducing pain and increasing function will be presented. Ample opportunity will be made available for questions. doi:10.1016/j.ejpain.2007.03.111
98 HIGH-CONCENTRATION CAPSAICIN FOR TREATMENT OF PHN AND HIV NEUROPATHY PAIN M. Backonja
ther, capsaicin may enjoy a renaissance according to preliminary studies of topical application in high concentration. Evidence, advantages and limitations of these topical treatment strategies are in the focus of this workshop. Further, the suggested underlying pain-relieving mechanisms will be discussed as well as the question, whether it is possible to predict the efficacy of topical agents in subgroups of patients. Supported by the Alexander von Humboldt-Foundation, the Deutsche Forschungsgemeinschaft (DFG Ba 1921/1-3), the German Ministry of Research and Education within the German Research Network on Neuropathic Pain (BMBF, 01EM 05/04) and Pfizer Germany (unrestricted educational grant). doi:10.1016/j.ejpain.2007.03.113
Department of Neurology, University of Wisconsin, Madison, WI, USA High-concentration capsaicin has been studied by now in a number of studies for treatment of pain in PHN and HIV neuropathy. Early phase studies demonstrated good tolerability, in spite of the fact that concentrations used were in order of magnitude higher then currently available commercial preparations, and prolonged efficacy. These observations lead to studies which explored the dose (in the case of topical agent such as high-concentration capsaicin duration of application is proportionate to the dose) range and duration of the analgesic effect. All of the studies conducted thus far have consistently demonstrated good tolerability and prolong analgesic effect which for most patients who obtain benefit lasts up to 3 months. Because capsaicin is a pungent agent traditional placebo cannot be used so as the control low concentration capsaicin was used, and in this case it was possible to demonstrate the efficacy of high-concentration capsaicin. doi:10.1016/j.ejpain.2007.03.112
99 TOPICAL LIDOCAINE AND CAPSAICIN: DOES THE NEUROPATHIC PAIN NEEDS A SECOND SKIN? G. Wasner Prince of Wales, Medical Research Institute, University of New South Wales, Randwick, NSW, Australia Division of Neurological Pian Research and Therapy, Department of Neurology, University Clinic SchleswigHolstein, Campus Kiel, Germany In recent years cutaneous application of lidocaine, e.g. via patches containing 5% lidocaine, has become a recommended treatment for neuropathic pain. Fur-
100 TOPICAL AND PERIPHERALLY ACTING ANALGESICS FOR NEUROPATHIC PAIN MANAGEMENT E. Alon *, M. Jaquenod-Linder, C. Wanner Schmid Department of Anesthesia, University Hospital of Zurich, Switzerland Topical anesthetics are being investigated as an additional option in pain management and can play an important role in the therapeutic armamentarium of the pain specialist. They may be effective in reducing pain and improving function in patients with a variety of neuropathic and non-neuropathic pain conditions. The mechanism of action of topical anesthetics is largely within the peripheral nervous system. However, recent clinical investigations suggest that the effect of topical anesthetics on peripheral processing of pain transmission may lead to the dampening of central pain mechanisms as well. Thus, indirectly, topical anesthetics may relieve the discomfort associated with central, as well as peripheral, pain states. Much of the recent clinical research on topical anesthetics has been conducted using the topical lidocaine 5% patch. Although the lidocaine patch is indicated for postherpetic neuralgia (PHN), several studies evaluated the safety and efficacy in patients with painful conditions other than PHN such as low back pain and osteoarthritis. These studies suggest that the lidocaine patch may also be effective for pain conditions not considered to be neuropathic in origin. The systemic absorption of lidocaine from the patch is minimal. The patch has demonstrated relief from pain and tactile allodynia with a minimal risk or systemic adverse effects or drug–drug interactions. Most adverse events occurred at the application sites; no
randomized to receive a single dose of investigational zoster vaccine or placebo. Subjects were actively followed for HZ with the aid of an interactive Automated Telephone Response System, and more than 95% of the enrolled subjects were successfully followed to the end of the Study. A HZ-specific assessment tool, the Zoster Brief Pain Inventory (ZBPI), was developed and validated to capture HZ pain and discomfort, including unpleasant sensations such as allodynia and pruritus not always characterized as pain by persons with HZ. Clinically significant PHN was defined as HZ-associated pain or discomfort rated as P3 (on a 0-to-10 scale) persisting or appearing more than 90 days after HZ rash onset. ZBPI worst pain scores <3 are not associated with significant decrements in quality of life or ability to carry out activities of daily living, and thus were not considered to represent clinically significant PHN. Zoster vaccine reduced the Incidence of clinically significant PHN by 66.5% (P < 0.001), and the reduction was identical in both age strata. The zoster vaccine was well tolerated, and it neither caused nor induced HZ [Oxman MN, et al. N Engl J Med 2005;352:2271–84]. Immunological assays at baseline confirmed a progressive loss of VZV-CMI with increasing age (P < 0.001), and no significant age-related change in titers of antibody to VZV (P = 0.75). At 6 weeks after vaccination, VZV immune responses in vaccine recipients were significantly increased over baseline (P < 0.001) and compared to responses in placebo recipients, and significant increases were sustained at 1, 2, and 3 years. VZV-CMI responses in the vaccine group were greater in subjects 60–69 years of age than in those P70 (P < 0.01). These age-related differences in VZVCMI were paralleled by age-related differences in the incidence and severity of PHN, and in the clinical efficacy of the zoster vaccine. These results will be discussed in relation to the neuropathology and mechanisms of PHN. doi:10.1016/j.ejpain.2007.03.109
96 INVASIVE TREATMENT OF HERPES ZOSTER AND POSTHERPETIC NEURALGIA A.J.M. van Wijck Pain Clinic, University Medical Center Utrecht, The Netherlands Several invasive treatments are used for the treatment of herpes zoster (HZ) postherpetic neuralgia (PHN). They include subcutaneous injections, peripheral nerve blocks, sympathetic blocks, epidural injections, intrathecal injections and spinal cord stimulation (Opstelten, 2004; Kumar, 2004). The intervention can be aimed at relieve of acute pain in HZ, prevention of PHN or treat-
S39
ment of PHN. The efficacy of invasive therapies for the treatment of acute pain has been established in several randomized controlled trials (RCTs). For prevention of PHN, results of 2 RCTs are conflicting. One trial that used an epidural catheter for multiple injections of bupivacaine and methylprednisolone showed a significant reduction of PHN (Pasqualucci, 2000). A second trial that used a single epidural injection with bupivacain and methylprednisolone showed no preventive effect on PHN (van Wijck, 2006). One trial showed reduction of pain in patients with PHN by intrathecal administration of methylprednisolone (Kotani, 2000). References Opstelten, W. et al. (2004). Interventions to prevent postherpetic neuralgia: cutaneous and percutaneous techniques. Pain, 107(3), 202–206. Kumar, V. et al. (2004). Neuraxial and sympathetic blocks in herpes zoster and postherpetic neuralgia: an appraisal of current evidence. Reg Anesth Pain Med, 29, 454–461. Pasqualucci, A. et al. (2000). Prevention of post-herpetic neuralgia: acyclovir and prednisolone versus epidural local anesthetic and methylprednisolone. Acta Anaesthesiol Scand, 44, 910–918. van Wijck, A. J. et al. (2006). The PINE study of epidural steroids and local anaesthetics to prevent postherpetic neuralgia: a randomised controlled trial. Lancet, 367, 219–224. Kotani, N. et al. (2000). Intrathecal Methylprednisolone for Intractable Postherpetic Neuralgia. N Engl J Med, 343, 1514–1519. doi:10.1016/j.ejpain.2007.03.110
Workshop – Therapy 4: TOPICAL AND TRANSDERMAL TREATMENTS FOR NEUROPATHIC PAIN
97 Workshop Summary: TOPICAL AND TRANSDERMAL TREATMENTS FOR NEUROPATHIC PAIN G. Gourlay Pain Management Unit, Flinders Medical Centre, Adelaide, Australia This Workshop will consider various topical and transdermal interventions for the treatment of a variety of neuropathic pain states. The focus will be clearly on treatment options as mechanistic and diagnostic issues will be covered in other Workshops at this Congress. The role of topical capsaicin in general, but particularly more recent information concerning high dose capsaicin patches will be presented by Dr. Backonja. In recent years cutaneous application of lignocaine via patches containing 5% lignocaine, has become a recommended treatment for neuropathic pain. Evidence, advantages and limitations of these topical treatment strategies will be presented by Dr. Wasner. Further, the possibility of predicting the efficacy of topical agents in
S40
Invited Presentations / Workshop – Therapy 4 / European Journal of Pain 11(S1) (2007) S1–S57
subgroups of patients will be discussed. Finally, Dr. Alon will consider the role of transdermal fentanyl and buprenorphine in the treatment of neuropathic pain. Evidence for the role of these interventions together with the strengths and limitations of each treatment modality in reducing pain and increasing function will be presented. Ample opportunity will be made available for questions. doi:10.1016/j.ejpain.2007.03.111
98 HIGH-CONCENTRATION CAPSAICIN FOR TREATMENT OF PHN AND HIV NEUROPATHY PAIN M. Backonja
ther, capsaicin may enjoy a renaissance according to preliminary studies of topical application in high concentration. Evidence, advantages and limitations of these topical treatment strategies are in the focus of this workshop. Further, the suggested underlying pain-relieving mechanisms will be discussed as well as the question, whether it is possible to predict the efficacy of topical agents in subgroups of patients. Supported by the Alexander von Humboldt-Foundation, the Deutsche Forschungsgemeinschaft (DFG Ba 1921/1-3), the German Ministry of Research and Education within the German Research Network on Neuropathic Pain (BMBF, 01EM 05/04) and Pfizer Germany (unrestricted educational grant). doi:10.1016/j.ejpain.2007.03.113
Department of Neurology, University of Wisconsin, Madison, WI, USA High-concentration capsaicin has been studied by now in a number of studies for treatment of pain in PHN and HIV neuropathy. Early phase studies demonstrated good tolerability, in spite of the fact that concentrations used were in order of magnitude higher then currently available commercial preparations, and prolonged efficacy. These observations lead to studies which explored the dose (in the case of topical agent such as high-concentration capsaicin duration of application is proportionate to the dose) range and duration of the analgesic effect. All of the studies conducted thus far have consistently demonstrated good tolerability and prolong analgesic effect which for most patients who obtain benefit lasts up to 3 months. Because capsaicin is a pungent agent traditional placebo cannot be used so as the control low concentration capsaicin was used, and in this case it was possible to demonstrate the efficacy of high-concentration capsaicin. doi:10.1016/j.ejpain.2007.03.112
99 TOPICAL LIDOCAINE AND CAPSAICIN: DOES THE NEUROPATHIC PAIN NEEDS A SECOND SKIN? G. Wasner Prince of Wales, Medical Research Institute, University of New South Wales, Randwick, NSW, Australia Division of Neurological Pian Research and Therapy, Department of Neurology, University Clinic SchleswigHolstein, Campus Kiel, Germany In recent years cutaneous application of lidocaine, e.g. via patches containing 5% lidocaine, has become a recommended treatment for neuropathic pain. Fur-
100 TOPICAL AND PERIPHERALLY ACTING ANALGESICS FOR NEUROPATHIC PAIN MANAGEMENT E. Alon *, M. Jaquenod-Linder, C. Wanner Schmid Department of Anesthesia, University Hospital of Zurich, Switzerland Topical anesthetics are being investigated as an additional option in pain management and can play an important role in the therapeutic armamentarium of the pain specialist. They may be effective in reducing pain and improving function in patients with a variety of neuropathic and non-neuropathic pain conditions. The mechanism of action of topical anesthetics is largely within the peripheral nervous system. However, recent clinical investigations suggest that the effect of topical anesthetics on peripheral processing of pain transmission may lead to the dampening of central pain mechanisms as well. Thus, indirectly, topical anesthetics may relieve the discomfort associated with central, as well as peripheral, pain states. Much of the recent clinical research on topical anesthetics has been conducted using the topical lidocaine 5% patch. Although the lidocaine patch is indicated for postherpetic neuralgia (PHN), several studies evaluated the safety and efficacy in patients with painful conditions other than PHN such as low back pain and osteoarthritis. These studies suggest that the lidocaine patch may also be effective for pain conditions not considered to be neuropathic in origin. The systemic absorption of lidocaine from the patch is minimal. The patch has demonstrated relief from pain and tactile allodynia with a minimal risk or systemic adverse effects or drug–drug interactions. Most adverse events occurred at the application sites; no