450 THE MECHANISMS OF MERIDIAN POINTS INJECTED BONE MARROW MESENCHYMAL STEM CELL IMPROVE NEUROPATHIC PAIN IN ZUCKER DIABETIC FATTY RATS

450 THE MECHANISMS OF MERIDIAN POINTS INJECTED BONE MARROW MESENCHYMAL STEM CELL IMPROVE NEUROPATHIC PAIN IN ZUCKER DIABETIC FATTY RATS

Posters / European Journal of Pain Supplements 4 (2010) 47–146 447 DOES TREATING THE PAIN HEAL THE BRAIN? ANATOMICAL AND FUNCTIONAL CHANGES IN PEDIAT...

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Posters / European Journal of Pain Supplements 4 (2010) 47–146

447 DOES TREATING THE PAIN HEAL THE BRAIN? ANATOMICAL AND FUNCTIONAL CHANGES IN PEDIATRIC COMPLEX REGIONAL PAIN SYNDROME AFTER MULTIDISCIPLINARY TREATMENT S. Sava1 , A. Drosos1 , A. Lebel1,2 , D. Leslie2,3,4 , N. Maleki5 , G. Pendse5 , M. Hogan3 , K. Olson3 , E. Firn3 , G. Chiang3 , L. Simons3 , V. Gaughan3 , D. Logan3 , C. Berde2,3,4 , L. Becerra1,5 , D. Borsook1,5 . 1 Pain/Analgesia Imaging Neuroscience (P.A.I.N.) Group, Radiology, Childrens Hospital Boston, Harvard Medical School, Waltham, 2 Anesthesiology, Perioperative and Pain Medicine, Childrens Hospital Boston, Harvard Medical School, Boston, 3 Mayo Family Pediatric Pain and Rehabilitation Center, Childrens Hospital Boston, Harvard Medical School, Waltham, 4 Pain Treatment Services, Childrens Hospital Boston, Harvard Medical School, Boston, 5 P.A.I.N. Group, McLean Hospital, Harvard Medical School, Belmont, MA, USA Introduction: The pain in pediatric complex regional pain syndrome (CRPS) usually resolves after several months, spontaneously or with therapy. In this study, we investigated longitudinal changes in psycho-functional, anatomical (cortical and subcortical volumes, white matter integrity) and functional measures (resting state-based connectivity) in a group of children and adolescents (10–18 years of age) with CRPS. Methods: Thirteen CRPS patients were tested during their painful episode and early recovery. Thirteen age- and gender-matched controls were scanned at similar intervals. Each study session included quantitative sensory testing and MR imaging on a 3T scanner. Measures of cortical thickness and subcortical volumes were obtained using Freesurfer (Fischl et al., Neuron 2002; 33(3): 341–355). For the diffusion tensor imaging (DTI) analysis, a voxelwise statistical analysis comparing the pre- and post-therapy FA maps was performed. Resting state based connectivity analysis was measured using a seed correlation based approach. Results: Our preliminary results show that CRPS patients had improved score on functional and psych-physical measures after treatment. These changes were accompanied by changes in cortical and subcortical volumes over the same period of time, mostly involving frontal and parietal regions as well as thalamus and the basal ganglia. Changes in functional connectivity patterns were observed in sensory (SI), emotional (cingulate; accumbens), integrative (inferior and superior parietal gyri), cognitive (medial frontal cortex) and motor areas (pallidum). Conclusions: By using a combined approach, we show that CRPS pain has widespread effects on brain measures in children and adolescents, and that some of these effects can reverse quickly after the pain subsides. 448 INVOLVEMENT OF NEURONAL NITRIC OXIDE SYNTHASE IN EXPERIMENTAL NEUROPATHIC PAIN IN RATS A. Giardine1 , L.R.G. Britto2 , M. Chacur1 . 1 Department of Anatomy, University of S˜ ao Paulo, Instituto of Biomedical Science, Sao Paulo, 2 Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, S˜ ao Paulo, Brazil Introduction: Several studies suggest that nitric oxide synthase (NOS) is an essential component of normal physiology of cells and that increased production of NO may underlie several pathophysiological conditions. Objectives: The aim of this project is to characterize the involvement of NOS in neuropathic pain. Methods: For the induction of neuropathic pain, surgery was performed on the sciatic nerve, according to the method described by Bennett & Xie (Pain 1988, 87–107). Hyperalgesia and allodynia were assessed using the rat paw pressure test (Randall & Sellito) and von Frey hairs, respectively, before and 7 and 14 days postinjury. Immunohistochemical assays were performed to evaluate nNOS expression. To characterize the involvement of neuronal NOS,

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an inhibitor (7-NI; 2 mg/50 ml) was administered by intratechal route 1 hour before testing. Results: A decrease of nociceptive thresholds of the animals was observed 7 and 14 days post-injury, when compared to baseline levels (before surgery). The administration of 7-NI was able to decrease hyperalgesia by the 7th and 14th day post-injury. On the other hand, the allodinic effect was decreased only when the inhibitor was administered by the 7th day post-injury. The immunohistochemistry assay showed a decrease of the number of labeled cells for nNOS in the experimental groups treated with the inhibitor, in both time points post-injury. Conclusions: Based on our results and literature data, we suggest a role of nNOS in neuropathic pain, acting as a modulator of nociceptive transmission, since the inhibitor of nNOS was able to reduce the sensitization induced by CCI-injury. 449 TREATMENT WITH TREADMILL EXERCISE DECREASED NEUROPATHIC PAIN IN TYPE 1 DIABETIC RATS Y.-W. Chen1 , C.-H. Hung2 , P.-L. Hsieh2 . 1 China Medical University, Taichung, 2 National Cheng Kung University, Tainan, Taiwan R.O.C. Introduction: Few reports on the role of treadmill exercise training on diabetic peripheral neuropathic pain (DPNP) have been reported. Objectives: We hypothesize that treadmill exercise may reduce DPNP and induce heat shock protein 72 (HSP72) expression in nerves of streptozotocin (STZ)-induced diabetic rats. Methods: Male Wistar rats were randomly assigned to four groups: normal sedentary group, normal exercise group, and diabetic rats with/without exercise training group. The trained rats ran on a treadmill 5 days/week, 30–60 min/day with an intensity of 20–25 m/min from Day 3 after STZ-injection. DPNP was evaluated by the withdrawal responses to heat or light touch stimuli, and HSP72 expression in spinal cord and peripheral nerves (the mixture of tibial, peroneal, and sural nerves) were determined by western blotting. Results: A decrease in mechanism threshold (tactile allodynia) and withdrawal latency (thermal hyperalgesia) was seen in the diabetic animals. Exercise training decreased STZ-induced allodynia or hyperalgesia, and normal exercise group showed no significant differences in allodynia or hyperalgesia compared with normal sedentary group. HSP72 expression in spinal cord, sciatic and peripheral nerves was significantly greater in diabetic rats with exercise training than those without exercise training. Conclusions: Treadmill exercise training induced HSP72 expression in the spinal cord, sciatic and peripheral nerves and conferred significant protection against DPNP in the diabetic rats. 450 THE MECHANISMS OF MERIDIAN POINTS INJECTED BONE MARROW MESENCHYMAL STEM CELL IMPROVE NEUROPATHIC PAIN IN ZUCKER DIABETIC FATTY RATS J.-X. Dong1 , C.-J. Zhu1 , P.-J. Rong2 . 1 Clinical Medical School of Chinese Medicine, Capital University of Medical Sciences, 2 Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China Introduction: To explore the mechanisms of meridian point injected Bone Marrow Mesenchymal Stem Cell improve blood flow and neuropathic pain in Zucker Diabetic Fatty rats. Objectives: 24 Zucker Diabetic Fatty (ZDF) rats were randomly divided into 3 groups: meridian points injection Mesenchymal Stem Cell (MSC) group (sanyinjiao, housanli, zhaohai, huantiao, yanglingquan acupoints were selected), thigh muscle injection (TMI) MSC group, and control group. Methods: MSC injection groups rats were received MSC transplantation. 3 weeks after injection of BM-MSC, in each treatment group, hindlimb adductor and gastrocnemius were

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Posters / European Journal of Pain Supplements 4 (2010) 47–146

got from the operative side. We examined immunohistochemical expression quantity of TGF-b1 and TNF-a, and the expression of VEGF-positive capillaries. a-SMA immunohistochemical staining showed small artery in skeletal muscle, calculation of the density of small arteries (number of arterioles/number of muscle fibers). Results: Immunohistochemical expression quantity of TGF-b1, TNFa, the expression of VEGF-positive capillaries and the density of small arteries of the MSC injection group were significantly increased (P < 0.01). Conclusions: Injected MSC along the meridian point, through the MSC secreted more VEGF, TGF-b1 and TNF-a to increased angiogenesis and arteriogenesis so as to improve the neuropathic pain. 451 CENTRAL NERVOUS SYSTEM ACTIVITY IS CRITICAL FOR METHADONE INDUCED ANALGESIA E. Rosenberg, N. Mogga. Anesthesiology, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA Introduction: It has recently been suggested that methadone exerts a substantial portion of its analgesic effect via the peripheral nervous system (Whistler, J. et al. The Journal of Pain 2009; 10: 369– 379). It is unknown whether direct administration of methadone to the peripheral nervous system will elicit analgesia. Objectives: To determine if methadone delivery to a peripheral nerve site following nerve injury will elicit analgesic behavior. Methods: Under an IACUC approved protocol, male Sprague Dawley rats received a sciatic nerve crush injury following baseline testing for Von Frey filament response. A non-irritating silastic catheter was secured alongside the nerve and immediately proximal to the injury site. At day 4 post-injury, hyperalgesic behavior was confirmed (<4g) and animals divided into subcutaneous methadone (n = 3) or perineural methadone administration (n = 4). A dose of 0.5 mg/kg in saline solution at physiologic temperature/pH was injected via the perineural catheter or subcutaneously. Animals were tested for Von Frey response at 30, 60, and 120 minutes. Results: Animals receiving subcutaneous (systemic) methadone showed a statistically significant improvement in analgesia at 120 minutes compared to baseline (15 g±0 vs. 3.18 g±0.57, p < 0.05) via one-way ANOVA. The perineural group failed to show significant difference from baseline at any time point. Conclusions: These findings demonstrate a lack of analgesic efficacy for aqueous methadone administration via perineural injection at a systemically effective dose. This suggests that while methadone may exert some of its action via the peripheral nervous system, central activity is still necessary for the production of analgesia. 452 A RANDOMIZED CONTROLLED TRIAL (RCT) USING DIFFERENT ACUPUNCTURE TECHNIQUES FOR BETTER PAIN RELIEF IN HOSPICE PATIENTS WITH CHRONIC CANCER PAIN R. Akhileswaran1 , W.T. Lim2 , S. Ong2 , F.H. Tong3 , S.B. Tan4 , H.C. Tan5 , J.-J.W. Chen5 . 1 Palliative Medicine, HCA Hospice Care, 2 Medical Oncology, National Cancer Center, 3 Traditional Chinese Medicine, Kwong Wai Shiu Hospital, 4 Singapore Clinical Research Institute, 5 Biostatistics Unit, National Cancer Center, Singapore, Singapore Introduction: A pilot study carried out at our hospice, showed that 82.4% of the patients treated with acupuncture had improved pain relief for their chronic cancer pain. 68% of patients had neuropathic or mixed pain. Based on this, a prospective RCT was carried out to study different acupuncture techniques for chronic cancer pain relief. Objective: To study the effectiveness of different acupuncture techniques in relieving chronic cancer pain in hospice patients. Methods: A double-blind RCT was carried out using three different acupuncture techniques. One was customized according to the patient’s pain (1), one was generalized for pain relief (2) and one

not specific for pain relief (3). Patients recieved 10 treatments, two times weekly for 5 weeks. The patient and clinical staff were blinded to the acupuncture technique used. Pain scores were taken before starting treatment, weekly during treatment, 1 week and 1 month after completing treatment. Results: Of the 30 patients treated, 12 (40%) had neuropathic pain, 11 (36.7%) nociceptive pain, and 7 (23.4%) mixed pains. 5/10 in treatment 1, 3/9 in treatment 2 and 7/11 in treatment 3 showed moderate to good responses. However, there was no statistically significant difference in the three techniques used. 8 patients were excluded from the analysis for different reasons. Details of the acupuncture techniques used and results of the analysis will be highlighted in the poster. Conclusions: This RCT with a small number of patients could not determine whether customized acupuncture techniques for pain relief were superior to generalized ones used for chronic cancer pain in hospice patients. 453 EFFICACY OF LOW LEVEL LASER THERAPY ON PAINFUL SENSORIMOTOR SYMPTOMS IN DIABETIC PATIENTS WITH POLYNEUROPATHY H. Bashiri. Internal Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran Introduction: Distal sensorimotor polyneuropathy (DSP) is one of the most common complaints of diabetic patients. DSP is abnormal tingling that often occurs in feet at night. Common medications are often ineffective and are associated with complication. Laser therapy maybe be a suitable alternative. Methods and materials: A total of 60 patients in Diabetes Research Center of Kermanshah University of Medical Sciences were studied. At first VAS (Visual Analogue Scale) and TCSS (Toronto Clinical Scoring System) were measured by an intrnist and then patients were been divided in two groups, the first group treated with low level laser (2.5 J/cm2 and wave length of 758 nm) and the second group with sham therapy, during 4 weeks. VAS and TCSS were measured before and 2 & 4 weeks after treatment. Results: 14 cases were male (23.3%) and 46 (77.7%) were female. All of patients had type 2 dibetes mellitus. Two groups were matched according to age, height, weight, duration of diabetes and HBA1C. VAS and TCSS values before and 2 & 4 weeks after treatment in case group had significant differences. But in control group there was no significant differences between above values. (p < 0.0001 and p < 0.881 respectively). Also comparison of VAS and TCSS values after treatment between two groups had meaningful differences (p < 0.0001). Conclusion: According to this study use of low level laser in treatment of diabetic sensorimotor polyneuropathy can be a suitable therapeutic option. However it seems complementary studies with larger sample size is needed for better judgment and decision making. 454 NON-PHARMACOLOGICAL TREATMENTS FOR TRIGEMINAL NEURALGIA I. Casanova, J. Porta-Etessam, B. Parejo, L. Gomez, A. Marcos, A. Vela, A. Guerrero, L. Galan. Neurology, Hospital Clinico San Carlos, Madrid, Spain Introduction: Neuromodulator drugs are the first line treatment for trigeminal neuralgia (TN). Even with correct medical treatment, there are up to 15% of patients without adequate control. Other options classically used in TN include several surgical and ablative techniques of the trigeminal nerve. Objectives: To report two patients with refractory-TN treated with non-pharmacological-non-invasive therapies. Methods: Patient 1: 65-year old male with right-V1 postherpetic-TN treated with repetitive-transcraneal-magnetic-stimulation (rTMS).