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388 CONTACT HEAT EVOKED POTENTIALS IN CAPSAICIN INDUCED HEAT HYPERALGESIA
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Posters / European Journal of Pain Supplements 4 (2010) 47–146
385 EFFECTS OF EARLY RETINIOC ACID TREATMENT ON INFLAMMATION IN A RAT MODEL OF CENTRAL NEUROPATHIC PAIN S. van Neerven1,2,3 , R. Deumens1 , R. Jaken1 , E. Joosten1 , J. Mey2 . 1 Department of Anesthesiology, Maastricht University Medical Centre, Maastricht, The Netherlands; 2 Institute of Biology 2, RWTH Aachen, Aachen, Germany; 3 EURON Graduate School of Neuroscience, Maastricht, The Netherlands Introduction: Neuroimmune responses following spinal cord injury have been shown to largely contribute to mechanical allodynia and immune-suppressive therapies may therefore be of specific interest in treatment of central neuropathic pain. Our laboratory previously showed that retinoic acid (RA) has highly potent anti-inflammatory effects. Objectives: Investigate the anti-inflammatory effect of retinoic acid in a rat model of central neuropathic pain. Methods: Female Sprague Dawley rats received intrathecal bolus injections of 0, 2.5, 10, or 100 ng all-trans RA at 48, 24, and/or 0 hrs before being subjected to contusion injury of the low thoracic (T9) spinal cord. Animals were sacrificed at 6 hrs following injury, when pro-inflammatory cytokines are known to reach peak-levels. Spinal cord tissues were processed for mRNA analysis for a wide range of pro-inflammatory molecules. Results: A strong induction of IL-1b (6.9-fold), IL-6 (12.5-fold), and a moderate increase of TNFa (1.4-fold) were observed at the spinal injury site at 6 hrs following injury. At this time point, the spread of increased cytokine transcripts did not reach more than three spinal levels. None of the intrathecal dosages of RA attenuate the injury-induced increased levels of cytokine transcripts. Moreover, prolonging the pre-treatment period was ineffective at decreasing cytokine transcripts. Conclusions: Intrathecal RA treatment does not attenuate the early rises in pro-inflammatory cytokine levels following spinal cord injury in the rat. Treatment of early spinal-cord-injury-induced inflammation and consequently central neuropathic pain using RA, therefore, requires further investigation including period-oftreatment and optimal drug delivery routes. 386 DURATION OF LEARNED PLACEBO ANALGESIC RESPONSES L. Colloca. University of Turin Medical School, Turin, Italy Introduction: In the last few years, there has been an increased emphasis on learning as a modulator factor of placebo analgesia because prior exposure to a benefit via pharmacological or biologically-significant cues powerfully change behavior and clinical outcomes. An important direction for translational research is to determine the resistance to extinction of a placebo-induced analgesia. Objectives: Here we probed the duration over time of conditioned placebo analgesic responses. Methods: The paradigm consisted in two sessions of conditioning and 4 sessions of testing whereby 144 phasic painful stimulations were delivered on the dorsum of foot. Placebo manipulation was obtained by pairing green light to stimuli that were lowered, whereas a red light was associated with a series of control painful stimuli (conditioning phase). All the stimuli were set as those of control during the testing phase following two conditioned sessions. At the end of each stimulation, pain intensity was assessed by means of Numerical Rating Scale (NRS), ranging from 0 = no pain to 10 = maximum pain. Results: After prior exposure to effective treatments and repetitive reinforcements, we observed strong long-lasting conditioned placebo analgesic responses to painful stimulations. In fact, these effects did not extinct over the four sessions of testing (session 1, p < 0.001; session 2, p < 0.001; session 3, p < 0.01; session 4, p < 0.001). Conclusions: These findings contribute to increase our knowledge about the effectiveness of placebos. From an ethical perspective, this
is important for considering the use of placebos in clinics. Learned placebo responses represent one of the most promising strategy to managing neuropathic pain. 387 OROFACIAL PAIN FOLLOWING TRAUMATIC EVENTS IN THE NECK T. Shinozaki1 , H. Kamo1 , K. Iwata2 , Y. Imamura1 . 1 Oral Diagnosis, 2 Physiology, Nihon University School of Dentistry, Tokyo, Japan Introduction: Recently, neuropathic component has been emphasized in the pain mechanism of whiplash injuries. It is known that some cervical conditions can lead to orofacial pain. Objective: This study was conducted to investigate whether or not orofacial pain can be elicited following cervical tissue injuries. Methods: Five patients suffering from chronic unilateral orofacial pain after a traumatic event of the neck that hadn’t been relieved by dental treatment were enrolled in this study. To identify the origin of the pain, peripheral sensory inputs from the orofacial tissues and deep cervical tissues were blocked with 1. Local infiltration of 2% lidocaine around the painful orofacial region (OI), 2. Trigger point injection (TPI) with 1% lidocaine in masticatory and superficial cervical muscles, and finally 3. Deep cervical plexus block (CPB) with normal saline followed by 1% lidocaine. Orofacial pain after each procedure was evaluated using a pain relief score (PRS) comparing with pain intensity before treatment. Results: OI led to an unsatisfactory pain relief. PRS varied from 3/10 to 7/10 after TPI in the masticatory and cervical muscles. CPB at the level of C3–5 showed a significant pain relief with lidocaine but not with normal saline. Conclusions: Pain relief obtained by CPB was significantly lower than that of other procedures. Persistent orofacial pain that hadn’t been relieved by any previous therapeutic interventions was significantly alleviated by CPB. The results obtained in this study showed a possibility that some kinds of orofacial pain may be due to peripheral/central sensitization following traumatic cervical events. 388 CONTACT HEAT EVOKED POTENTIALS IN CAPSAICIN INDUCED HEAT HYPERALGESIA C.S. Madsen1 , N.B. Finnerup1 , B. Johnsen2 , A. Fuglsang-Frederiksen2 , T.S. Jensen1 . 1 Danish Pain Research Center, 2 Department of Clinical Neurophysiology, Aarhus University Hospital, Aarhus, Denmark Introduction: Capsaicin evoked sensory symptoms mimic the symptoms seen in neuropathic pain, but there is limited knowledge about the contribution of C and A delta fibers in capsaicin induced heat hyperalgesia. Objectives: To examine changes in perceived pain intensity and heat evoked potentials following capsaicin application. Methods: Twenty heat stimuli of 51°C were delivered using the contact heat evoked potential stimulator (CHEPS) and heat hyperalgesia was induced by topical application of 200 ml capsaicin (5%) on the dorsum of both hands. At the left wrist, a selective A delta nerve fiber block was performed by superficial radial nerve compression before capsaicin application. Results: We have preliminary data from 18 subjects. On the right arm, capsaicin yielded a decrease in N2 latency from mean 344.1±38.0 ms to 308.2±39.8 ms recorded from the vertex (Cz) position (p = 0.004, paired t-test) and an increase in pain ratings (p < 0.001). On the left arm, the A delta fiber blockade caused a decrease in heat evoked pain ratings (p < 0.001) and reproducible ultra-late CHEPs (>1000 ms) were recorded in 2 subjects. The subsequent capsaicin application caused an increase in heat evoked pain (p = 0.032) and ultra-late CHEPs were recorded in 10 subjects. Conclusions: Our findings suggest that capsaicin facilitates both A delta and C fiber mediated responses to heat.
Posters / European Journal of Pain Supplements 4 (2010) 47–146
385 EFFECTS OF EARLY RETINIOC ACID TREATMENT ON INFLAMMATION IN A RAT MODEL OF CENTRAL NEUROPATHIC PAIN S. van Neerven1,2,3 , R. Deumens1 , R. Jaken1 , E. Joosten1 , J. Mey2 . 1 Department of Anesthesiology, Maastricht University Medical Centre, Maastricht, The Netherlands; 2 Institute of Biology 2, RWTH Aachen, Aachen, Germany; 3 EURON Graduate School of Neuroscience, Maastricht, The Netherlands Introduction: Neuroimmune responses following spinal cord injury have been shown to largely contribute to mechanical allodynia and immune-suppressive therapies may therefore be of specific interest in treatment of central neuropathic pain. Our laboratory previously showed that retinoic acid (RA) has highly potent anti-inflammatory effects. Objectives: Investigate the anti-inflammatory effect of retinoic acid in a rat model of central neuropathic pain. Methods: Female Sprague Dawley rats received intrathecal bolus injections of 0, 2.5, 10, or 100 ng all-trans RA at 48, 24, and/or 0 hrs before being subjected to contusion injury of the low thoracic (T9) spinal cord. Animals were sacrificed at 6 hrs following injury, when pro-inflammatory cytokines are known to reach peak-levels. Spinal cord tissues were processed for mRNA analysis for a wide range of pro-inflammatory molecules. Results: A strong induction of IL-1b (6.9-fold), IL-6 (12.5-fold), and a moderate increase of TNFa (1.4-fold) were observed at the spinal injury site at 6 hrs following injury. At this time point, the spread of increased cytokine transcripts did not reach more than three spinal levels. None of the intrathecal dosages of RA attenuate the injury-induced increased levels of cytokine transcripts. Moreover, prolonging the pre-treatment period was ineffective at decreasing cytokine transcripts. Conclusions: Intrathecal RA treatment does not attenuate the early rises in pro-inflammatory cytokine levels following spinal cord injury in the rat. Treatment of early spinal-cord-injury-induced inflammation and consequently central neuropathic pain using RA, therefore, requires further investigation including period-oftreatment and optimal drug delivery routes. 386 DURATION OF LEARNED PLACEBO ANALGESIC RESPONSES L. Colloca. University of Turin Medical School, Turin, Italy Introduction: In the last few years, there has been an increased emphasis on learning as a modulator factor of placebo analgesia because prior exposure to a benefit via pharmacological or biologically-significant cues powerfully change behavior and clinical outcomes. An important direction for translational research is to determine the resistance to extinction of a placebo-induced analgesia. Objectives: Here we probed the duration over time of conditioned placebo analgesic responses. Methods: The paradigm consisted in two sessions of conditioning and 4 sessions of testing whereby 144 phasic painful stimulations were delivered on the dorsum of foot. Placebo manipulation was obtained by pairing green light to stimuli that were lowered, whereas a red light was associated with a series of control painful stimuli (conditioning phase). All the stimuli were set as those of control during the testing phase following two conditioned sessions. At the end of each stimulation, pain intensity was assessed by means of Numerical Rating Scale (NRS), ranging from 0 = no pain to 10 = maximum pain. Results: After prior exposure to effective treatments and repetitive reinforcements, we observed strong long-lasting conditioned placebo analgesic responses to painful stimulations. In fact, these effects did not extinct over the four sessions of testing (session 1, p < 0.001; session 2, p < 0.001; session 3, p < 0.01; session 4, p < 0.001). Conclusions: These findings contribute to increase our knowledge about the effectiveness of placebos. From an ethical perspective, this
is important for considering the use of placebos in clinics. Learned placebo responses represent one of the most promising strategy to managing neuropathic pain. 387 OROFACIAL PAIN FOLLOWING TRAUMATIC EVENTS IN THE NECK T. Shinozaki1 , H. Kamo1 , K. Iwata2 , Y. Imamura1 . 1 Oral Diagnosis, 2 Physiology, Nihon University School of Dentistry, Tokyo, Japan Introduction: Recently, neuropathic component has been emphasized in the pain mechanism of whiplash injuries. It is known that some cervical conditions can lead to orofacial pain. Objective: This study was conducted to investigate whether or not orofacial pain can be elicited following cervical tissue injuries. Methods: Five patients suffering from chronic unilateral orofacial pain after a traumatic event of the neck that hadn’t been relieved by dental treatment were enrolled in this study. To identify the origin of the pain, peripheral sensory inputs from the orofacial tissues and deep cervical tissues were blocked with 1. Local infiltration of 2% lidocaine around the painful orofacial region (OI), 2. Trigger point injection (TPI) with 1% lidocaine in masticatory and superficial cervical muscles, and finally 3. Deep cervical plexus block (CPB) with normal saline followed by 1% lidocaine. Orofacial pain after each procedure was evaluated using a pain relief score (PRS) comparing with pain intensity before treatment. Results: OI led to an unsatisfactory pain relief. PRS varied from 3/10 to 7/10 after TPI in the masticatory and cervical muscles. CPB at the level of C3–5 showed a significant pain relief with lidocaine but not with normal saline. Conclusions: Pain relief obtained by CPB was significantly lower than that of other procedures. Persistent orofacial pain that hadn’t been relieved by any previous therapeutic interventions was significantly alleviated by CPB. The results obtained in this study showed a possibility that some kinds of orofacial pain may be due to peripheral/central sensitization following traumatic cervical events. 388 CONTACT HEAT EVOKED POTENTIALS IN CAPSAICIN INDUCED HEAT HYPERALGESIA C.S. Madsen1 , N.B. Finnerup1 , B. Johnsen2 , A. Fuglsang-Frederiksen2 , T.S. Jensen1 . 1 Danish Pain Research Center, 2 Department of Clinical Neurophysiology, Aarhus University Hospital, Aarhus, Denmark Introduction: Capsaicin evoked sensory symptoms mimic the symptoms seen in neuropathic pain, but there is limited knowledge about the contribution of C and A delta fibers in capsaicin induced heat hyperalgesia. Objectives: To examine changes in perceived pain intensity and heat evoked potentials following capsaicin application. Methods: Twenty heat stimuli of 51°C were delivered using the contact heat evoked potential stimulator (CHEPS) and heat hyperalgesia was induced by topical application of 200 ml capsaicin (5%) on the dorsum of both hands. At the left wrist, a selective A delta nerve fiber block was performed by superficial radial nerve compression before capsaicin application. Results: We have preliminary data from 18 subjects. On the right arm, capsaicin yielded a decrease in N2 latency from mean 344.1±38.0 ms to 308.2±39.8 ms recorded from the vertex (Cz) position (p = 0.004, paired t-test) and an increase in pain ratings (p < 0.001). On the left arm, the A delta fiber blockade caused a decrease in heat evoked pain ratings (p < 0.001) and reproducible ultra-late CHEPs (>1000 ms) were recorded in 2 subjects. The subsequent capsaicin application caused an increase in heat evoked pain (p = 0.032) and ultra-late CHEPs were recorded in 10 subjects. Conclusions: Our findings suggest that capsaicin facilitates both A delta and C fiber mediated responses to heat.