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278 PLACEBO RESPONSE CHARACTERISTICS IN EIGHT PREGABALIN DIABETIC PERIPHERAL NEUROPATHY TRIALS
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Posters / European Journal of Pain Supplements 4 (2010) 47–146
This factor structure may inform us about mechanisms of NeP and guide targeted therapies. Stabbing and heavy pain qualities predict pregabalin pain response in patients with painful DPN and PHN. However, they may not be as useful when baseline pain is incorporated in the predictive model. 276 PERIPHERAL NERVE STIMULATION IN PATIENTS WITH CHRONIC NEUROPATHIC PAIN AFTER SURGERY T.P. Enggaard, C. Scherer, C. Andersen. Department of Anaesthesiology and Intensive Care Medicine, Odense University Hospital, Odense, Denmark Introduction: Neuropathic pain due to peripheral nerve lesions after surgery is described as the most important cause of long-term postsurgical pain and may represent a major unrecognised clinical problem [1]. Pharmacological treatment has shown to relieve neuropathic pain. However, adverse effects are often problematic [2]. Non-pharmacological treatment such as Transcutaneous Electrical Nerve Stimulation (TENS) can be an option, since patients with peripheral neuropathic pain are among the best TENS-responding groups [3]. However, the use of longterm treatment with TENS is limited due to inconvenience for the patients. Peripheral nerve stimulation (PNS) by subcutaneous electrodes connected to an Implanted Pulse Generator (IPG) has undergone technical refinements in recent years and may be an alternative to TENS. Objectives: Presentation of two case reports with use of peripheral nerve stimulation in patients with neuropathic pain after surgery. Methods: Long-term follow-up with focus on how to optimise the procedures and minimise the costs. Results: Both patients experienced long-term analgesic effect with PNS. However, battery life time of the IPGs was less than 12 months due to high energy consumption. Rechargeable IPGs were in both cases successfully implanted. Conclusions: In two cases of otherwise intractable neuropathic pain after surgery, the patients experienced significant pain relief due to peripheral nerve stimulation. Rechargeable pulse generators could be an option in case of high energy consumption using conventional implanted pulse generators. Reference(s) [1] Lancet 2006; 367: 1618–25. [2] Wall and Melzack’s Textbook of pain, 5th Edition, chapter 31+32. [3] Wall and Melzack’s Textbook of pain, 5th Edition, chapter 38.
277 TREATMENT INDUCED DIABETIC NEUROPATHY – AN ACUTE, REVERSIBLE, PAINFUL SMALL FIBER AND AUTONOMIC NEUROPATHY C. Gibbons, R. Freeman. Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Introduction: Acute neuropathic pain may occur in diabetic patients in association with rigorous glycemic control, also known as ‘insulin neuritis”. The mechanism and clinical features are not fully elucidated. Objective: To describe the clinical, laboratory and histological features, and outcome of diabetic patients presenting with acute painful neuropathy. Methods: Sixteen subjects had neurologic examinations, autonomic testing, laboratory studies, retinal, renal and pain assessments over 18 months. Selected subjects had skin biopsies for evaluation of intra-epidermal nerve fiber density. Results: All subjects developed severe pain (10/10) within 8 weeks of glucose control. There was a high prevalence of allodynia, hyperalgesia, autonomic symptoms and test abnormalities. Reduced intra-epidermal nerve fiber density (IENFD) was seen in all tested subjects. After 18 months of glycemic control, there were substantial improvements in pain, autonomic symptoms, autonomic test results
and IENFD. Greater improvements autonomic symptoms and test results were seen in patients with type 1 diabetes (P < 0.001). Other microvascular complications, retinopathy and nephropathy – thought to be mediated by proinflammatory cytokines – worsened in all subjects. Conclusion: Treatment induced neuropathy is characterized by acute, severe pain, peripheral nerve degeneration and autonomic dysfunction after rapid glucose regulation. Generalized worsening of microvascular disease following intensive glycemic therapy suggests a common underlying pathophysiological mechanism. Proinflammatory cytokines may be implicated. Symptoms, signs and objective measures of small myelinated and unmyelinated nerve fibers can improve in diabetic patients despite a history of poor glucose control. These data may have implications for neuropathic pain therapeutic trials. 278 PLACEBO RESPONSE CHARACTERISTICS IN EIGHT PREGABALIN DIABETIC PERIPHERAL NEUROPATHY TRIALS R. Freeman1 , B. Emir2 , E. Whalen2 , Y. Xu2 , T.K. Murphy2 . 1 Beth Israel Deaconess Medical Center, Boston, MA, 2 Pfizer Inc., New York, NY, USA Introduction: A high placebo-response diminishes the likelihood of detecting drug effect in clinical trials. Identifying factors associated with placebo-response in neuropathic pain trials may lead to clinical trial designs with lower placebo-response and increase the likelihood of detecting efficacy. Objectives: To analyze features that increase the placebo-response in 4 High Placebo-Response (HPR = reduction in weekly mean pain score (MPS) at last visit >2) pregabalin studies of patients with painful diabetic peripheral neuropathy and identify predictors of placebo-response. Methods: The 4 HPR studies were compared with 4 low placeboresponse (LPR) studies. We compared the HPR and LPR studies with respect to age, gender and baseline MPS. Results: Two HPR trials were conducted before and 2 after the pregabalin approval. HPR trials tended to have greater likelihood of receiving active drug in treatment arms [Active to placebo ratios in HPR studies: 4:1-(1) and 2:1-(3) vs LPR studies: 3:1-(1), 2:1-(1) and 1:1-(2)]. HPR studies had higher placebo relief in MPS than LPR studies in elderly patients (age ≥60), −2.31 vs. −1.09. Patients aged <60 showed little difference in placebo-response. Among patients with severe baseline MPS, HPR studies had higher placebo relief in MPS than LPR studies, −2.67 vs. −1.39, however, patients with moderate baseline MPS showed little difference in placeboresponse, −1.55 and −1.14, respectively. Conclusions: HPR trials tended to have a high active drug to placebo ratio. Elderly patients and patients with severe baseline pain were observed to have a higher placebo response than younger or moderate baseline pain patients. 279 NEW TECHNIQUES TREATING ELDERLY PATIENTS WITH RADICULAR PAIN & NEUROPATHIC SYMPTOMS USING INTERSPINOUS PROCESS IMPLANTS (MLIF) FOR SEVERE LUMBAR SPONDYLOSIS S. Eidelson, H. Geisse, J. Fleming, D. Eidelson. South Palm Orthospine Institute, Delray Beach, FL, USA Study Design: Surgical procedures pose an increased risk of postoperative complications when patients are elderly with multiple comorbidities. The comorbidities currently considered to increase surgical risk include heart disease, diabetes, obesity, and hypertension. Further characterization of patient’s postoperative complications in relation to comorbidities suggests that procedures requiring less surgical time and blood loss lower perioperative complications. In this pilot study, 75 patients from 66 to 88 years of age were studied. The investigators seek to provide clinical results using less invasive spinal implants as an alternative to more complex traditional invasive surgical procedures.
Posters / European Journal of Pain Supplements 4 (2010) 47–146
This factor structure may inform us about mechanisms of NeP and guide targeted therapies. Stabbing and heavy pain qualities predict pregabalin pain response in patients with painful DPN and PHN. However, they may not be as useful when baseline pain is incorporated in the predictive model. 276 PERIPHERAL NERVE STIMULATION IN PATIENTS WITH CHRONIC NEUROPATHIC PAIN AFTER SURGERY T.P. Enggaard, C. Scherer, C. Andersen. Department of Anaesthesiology and Intensive Care Medicine, Odense University Hospital, Odense, Denmark Introduction: Neuropathic pain due to peripheral nerve lesions after surgery is described as the most important cause of long-term postsurgical pain and may represent a major unrecognised clinical problem [1]. Pharmacological treatment has shown to relieve neuropathic pain. However, adverse effects are often problematic [2]. Non-pharmacological treatment such as Transcutaneous Electrical Nerve Stimulation (TENS) can be an option, since patients with peripheral neuropathic pain are among the best TENS-responding groups [3]. However, the use of longterm treatment with TENS is limited due to inconvenience for the patients. Peripheral nerve stimulation (PNS) by subcutaneous electrodes connected to an Implanted Pulse Generator (IPG) has undergone technical refinements in recent years and may be an alternative to TENS. Objectives: Presentation of two case reports with use of peripheral nerve stimulation in patients with neuropathic pain after surgery. Methods: Long-term follow-up with focus on how to optimise the procedures and minimise the costs. Results: Both patients experienced long-term analgesic effect with PNS. However, battery life time of the IPGs was less than 12 months due to high energy consumption. Rechargeable IPGs were in both cases successfully implanted. Conclusions: In two cases of otherwise intractable neuropathic pain after surgery, the patients experienced significant pain relief due to peripheral nerve stimulation. Rechargeable pulse generators could be an option in case of high energy consumption using conventional implanted pulse generators. Reference(s) [1] Lancet 2006; 367: 1618–25. [2] Wall and Melzack’s Textbook of pain, 5th Edition, chapter 31+32. [3] Wall and Melzack’s Textbook of pain, 5th Edition, chapter 38.
277 TREATMENT INDUCED DIABETIC NEUROPATHY – AN ACUTE, REVERSIBLE, PAINFUL SMALL FIBER AND AUTONOMIC NEUROPATHY C. Gibbons, R. Freeman. Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Introduction: Acute neuropathic pain may occur in diabetic patients in association with rigorous glycemic control, also known as ‘insulin neuritis”. The mechanism and clinical features are not fully elucidated. Objective: To describe the clinical, laboratory and histological features, and outcome of diabetic patients presenting with acute painful neuropathy. Methods: Sixteen subjects had neurologic examinations, autonomic testing, laboratory studies, retinal, renal and pain assessments over 18 months. Selected subjects had skin biopsies for evaluation of intra-epidermal nerve fiber density. Results: All subjects developed severe pain (10/10) within 8 weeks of glucose control. There was a high prevalence of allodynia, hyperalgesia, autonomic symptoms and test abnormalities. Reduced intra-epidermal nerve fiber density (IENFD) was seen in all tested subjects. After 18 months of glycemic control, there were substantial improvements in pain, autonomic symptoms, autonomic test results
and IENFD. Greater improvements autonomic symptoms and test results were seen in patients with type 1 diabetes (P < 0.001). Other microvascular complications, retinopathy and nephropathy – thought to be mediated by proinflammatory cytokines – worsened in all subjects. Conclusion: Treatment induced neuropathy is characterized by acute, severe pain, peripheral nerve degeneration and autonomic dysfunction after rapid glucose regulation. Generalized worsening of microvascular disease following intensive glycemic therapy suggests a common underlying pathophysiological mechanism. Proinflammatory cytokines may be implicated. Symptoms, signs and objective measures of small myelinated and unmyelinated nerve fibers can improve in diabetic patients despite a history of poor glucose control. These data may have implications for neuropathic pain therapeutic trials. 278 PLACEBO RESPONSE CHARACTERISTICS IN EIGHT PREGABALIN DIABETIC PERIPHERAL NEUROPATHY TRIALS R. Freeman1 , B. Emir2 , E. Whalen2 , Y. Xu2 , T.K. Murphy2 . 1 Beth Israel Deaconess Medical Center, Boston, MA, 2 Pfizer Inc., New York, NY, USA Introduction: A high placebo-response diminishes the likelihood of detecting drug effect in clinical trials. Identifying factors associated with placebo-response in neuropathic pain trials may lead to clinical trial designs with lower placebo-response and increase the likelihood of detecting efficacy. Objectives: To analyze features that increase the placebo-response in 4 High Placebo-Response (HPR = reduction in weekly mean pain score (MPS) at last visit >2) pregabalin studies of patients with painful diabetic peripheral neuropathy and identify predictors of placebo-response. Methods: The 4 HPR studies were compared with 4 low placeboresponse (LPR) studies. We compared the HPR and LPR studies with respect to age, gender and baseline MPS. Results: Two HPR trials were conducted before and 2 after the pregabalin approval. HPR trials tended to have greater likelihood of receiving active drug in treatment arms [Active to placebo ratios in HPR studies: 4:1-(1) and 2:1-(3) vs LPR studies: 3:1-(1), 2:1-(1) and 1:1-(2)]. HPR studies had higher placebo relief in MPS than LPR studies in elderly patients (age ≥60), −2.31 vs. −1.09. Patients aged <60 showed little difference in placebo-response. Among patients with severe baseline MPS, HPR studies had higher placebo relief in MPS than LPR studies, −2.67 vs. −1.39, however, patients with moderate baseline MPS showed little difference in placeboresponse, −1.55 and −1.14, respectively. Conclusions: HPR trials tended to have a high active drug to placebo ratio. Elderly patients and patients with severe baseline pain were observed to have a higher placebo response than younger or moderate baseline pain patients. 279 NEW TECHNIQUES TREATING ELDERLY PATIENTS WITH RADICULAR PAIN & NEUROPATHIC SYMPTOMS USING INTERSPINOUS PROCESS IMPLANTS (MLIF) FOR SEVERE LUMBAR SPONDYLOSIS S. Eidelson, H. Geisse, J. Fleming, D. Eidelson. South Palm Orthospine Institute, Delray Beach, FL, USA Study Design: Surgical procedures pose an increased risk of postoperative complications when patients are elderly with multiple comorbidities. The comorbidities currently considered to increase surgical risk include heart disease, diabetes, obesity, and hypertension. Further characterization of patient’s postoperative complications in relation to comorbidities suggests that procedures requiring less surgical time and blood loss lower perioperative complications. In this pilot study, 75 patients from 66 to 88 years of age were studied. The investigators seek to provide clinical results using less invasive spinal implants as an alternative to more complex traditional invasive surgical procedures.