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209 MICROSTRUCTURAL CHANGES IN RAT BRAIN DUE TO CHRONIC PELVIC PAIN: A DIFFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING STUDY
Topic B: SYSTEMS (PHYSIOLOGY, ANATOMY, ANIMAL MODELS)
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taneous activity, increased responses to noxious peripheral stimulation and increased central glutamatergic drive in ON-cells) may contribute to neuropathic hypersensitivity in the SNI model.
Discussion: The results of this study show, for the first time, the hyperalgesic effects of a more prolonged systemic administration of ET-1, stressing its potential role in different pathological clinical conditions.
207 ENHANCED EFFICACY OF CARBAMAZEPINE IN A RAT MODEL OF CANCER-INDUCED BONE PAIN
209 MICROSTRUCTURAL CHANGES IN RAT BRAIN DUE TO CHRONIC PELVIC PAIN: A DIFFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING STUDY
R.M. Gordon-Williams ° , C.E. Urch, A.H. Dickenson. Dept. Pharmacology, University College London, UK Background & Aims: Pain resulting from metastases to bone is a frequent problem facing clinicians, of which breakthrough pain is the most problematic. In our model of Cancer-Induced Bone pain (CIBP), development of pain-like behaviours correlates with increasing responses of superficial and deep wide dynamic range (WDR) dorsal horn (DH) neurones. Abnormal sodium channel activity may contribute to these changes. Therefore carbamazepine, efficacious in trigeminal neuralgia and in models of neuropathic and inflammatory pain, was studied on DH neuronal responses in CIBP. Materials & Methods: MRMT-1 carcinoma cells were injected into the left tibia of male Sprague-Dawley rats and pain behaviours were assessed by ambulatory score, withdrawal to von Frey filaments and acetone. At peak behaviour (Post-op days 15−18), the effect of subcutaneous carbamazepine (1, 10, 25 mg/kg) was studied on responses of DH WDR neurones to electrical, von Frey and thermal stimuli in both sham and MRMT halothane anaesthetised rats using in-vivo extracellular recordings. Results: MRMT-1 injection caused development of pain-like behaviour and hyperexcitable responses of DH WDR neurones to all stimuli. In MRMT-1 group 25 mg/kg significantly reduced neuronal responses to mechanical stimuli (6 g), noxious heat (>40ºC), as well as input, C fibre and Post-Discharge measures (p < 0.05). In shams no significant effects were seen at any dose. Conclusions: Carbamazepine is effective at reducing evoked neuronal responses only in MRMT-1 injected animals, indicating pathophysiological changes in CIBP allow the actions of carbamazepine to become apparent. These results suggest that carbamazepine may be a useful adjuvant therapy in painful bony metastases.
M. Hascalik1 ° , H.M. Karakas2 , O. Celik3 , A.K. Firat2 , S. Hascalik3 . Clinic, Yesilyurt State Hospital, Malatya, 2 Department of Radiology, School of Medicine, University of Inonu, Malatya, 3 Department of Obstetrics and Gynecology, School of Medicine, University of Inonu, Malatya, Turkey 1 Anesthesiology
Background: Chronic pelvic pain is a non-malignant pain that is perceived in the structures of female pelvis. It must be continuous or recurrent for at least 6 months. Although pain signals are important factors of the organism’s survival, they have to be down regulated to prevent any severe disturbance of the organism’s function. In this study, effects of acute and chronic noxious stimuli on the diffusional characteristics of female rat brains were investigated. Methods: Ten adult Wistar-albino female rats were imaged with a 1.5 T clinical MR scanner. Hypertonic saline was intraperitoneally given on a daily basis for 15 days as a pain-inciting agent. Diffusion weighted images (DWI) were obtained at prestimulus, and at 1st and 15th day after the initial saline administration and apparent diffusion coefficient (ADC) maps were constructed. Results: Cerebral ADC values were insignificantly decreased at 1st day relative to prestimulus period (p = 0.187). ADC values were significantly increased between the 1st (737±23 mm2 /s × 10−3 ) and the 15th day (837±91 mm2 /s × 10−3 ) to exceed prestimulus values (777±67 mm2 /s × 10−3 ) (p < 0.002). The difference between ADC values of prestimulus period and the 15th day was roughly significant (p = 0.054). Conclusion: These results reflect the presence of transient microstructural alterations that develop during chronic irritation.
208 SIGNS OF ALTERED NOCICEPTION AFTER PROLONGED ADMINISTRATION OF ENDOTHELIN-1 IN RATS K. Deseure1 , G. Hans1,2 ° . 1 Laboratory for Pain Research/University of Antwerp, 2 Multidisciplinary Pain Center/Antwerp University Hospital, Belgium Introduction: Increasing evidence indicates that Endothelin-1 (ET-1) plays a role in peripheral nociceptive signalling. ET-1 is shown to be involved in the pathogenesis of pain states ranging from trauma to cancer. However, until now all behavioural and neurophysiological studies have been based on acute administration of ET-1. We investigated the effects of a more prolonged administration of ET-1 on thermal and mechanical hyperalgesia. Methodology: Sprague-Dawley rats (n = 12) were habituated to the different testing procedures (hot plate testing, von Frey stimulation and pin prick testing) on days −2 and −1. Baseline values were obtained one day before pump implantation (day −1). Rats were subcutaneously implanted with osmotic minipumps that released 22.8mg of ET-1/day. Rats were tested on post-pump days +2, +3, +5, +7, +10 and +17. Results: Rats treated with ET-1 developed thermal hyperalgesia from postoperative day 3 till the end of ET-1 treatment (day +7). This effect gained statistical significance on day +7. Three days after pump removal (day +10), hot plate latencies returned to the normal, preoperative values. ET-1 treated animals also displayed signs of increased sensitivity to both von Frey hair as well as pin prick stimulation of the cutaneous dorsal area where the ET-1 was released into the subcutaneous tissue. Animals also displayed a clinical pattern of increased body shaking on days +2 and +3.
210 ULTRASTRUCTURAL STUDY ABOUT THE NEUROPATHIC PAIN FOLLOWING LUMBAR SPINAL LAMINECTOMY C.Y. Tseng1 , P.Y. Chen1 , C.F. Huang3 , C.H. Chien1 , I.M. Jou2 ° . 1 Department of Anatomy, 2 Department of Orthopedics, National Cheng-Kung University, Tainan, 3 Department of Neurology, Sin-Lau Christian Hospital, Tainan, Taiwan Background & aims: Lumbar laminectomy is a surgical procedure, which is often performed to relieve the serious nerve root compression in chronic low back pain. Unfortunately, continuous pain symptom might be persisting in about 40% patients following this procedure. There are many causes of this pain syndrome and the most common one is epidural fibrosis. Numerous reports suggest that scar fibrosis causes recurrent radicular pain. By our previous animal study, the scar tissue has minimal compression effect under light microscopy, but the scar fibrosis may induce neovascularization and axon swelling in cauda equine after laminectomy in rats. In this study, we first investigated the ultrastructural changes in the nerve roots after laminectomy in rats. Furthermore, immunohistochemistry
S57
taneous activity, increased responses to noxious peripheral stimulation and increased central glutamatergic drive in ON-cells) may contribute to neuropathic hypersensitivity in the SNI model.
Discussion: The results of this study show, for the first time, the hyperalgesic effects of a more prolonged systemic administration of ET-1, stressing its potential role in different pathological clinical conditions.
207 ENHANCED EFFICACY OF CARBAMAZEPINE IN A RAT MODEL OF CANCER-INDUCED BONE PAIN
209 MICROSTRUCTURAL CHANGES IN RAT BRAIN DUE TO CHRONIC PELVIC PAIN: A DIFFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING STUDY
R.M. Gordon-Williams ° , C.E. Urch, A.H. Dickenson. Dept. Pharmacology, University College London, UK Background & Aims: Pain resulting from metastases to bone is a frequent problem facing clinicians, of which breakthrough pain is the most problematic. In our model of Cancer-Induced Bone pain (CIBP), development of pain-like behaviours correlates with increasing responses of superficial and deep wide dynamic range (WDR) dorsal horn (DH) neurones. Abnormal sodium channel activity may contribute to these changes. Therefore carbamazepine, efficacious in trigeminal neuralgia and in models of neuropathic and inflammatory pain, was studied on DH neuronal responses in CIBP. Materials & Methods: MRMT-1 carcinoma cells were injected into the left tibia of male Sprague-Dawley rats and pain behaviours were assessed by ambulatory score, withdrawal to von Frey filaments and acetone. At peak behaviour (Post-op days 15−18), the effect of subcutaneous carbamazepine (1, 10, 25 mg/kg) was studied on responses of DH WDR neurones to electrical, von Frey and thermal stimuli in both sham and MRMT halothane anaesthetised rats using in-vivo extracellular recordings. Results: MRMT-1 injection caused development of pain-like behaviour and hyperexcitable responses of DH WDR neurones to all stimuli. In MRMT-1 group 25 mg/kg significantly reduced neuronal responses to mechanical stimuli (6 g), noxious heat (>40ºC), as well as input, C fibre and Post-Discharge measures (p < 0.05). In shams no significant effects were seen at any dose. Conclusions: Carbamazepine is effective at reducing evoked neuronal responses only in MRMT-1 injected animals, indicating pathophysiological changes in CIBP allow the actions of carbamazepine to become apparent. These results suggest that carbamazepine may be a useful adjuvant therapy in painful bony metastases.
M. Hascalik1 ° , H.M. Karakas2 , O. Celik3 , A.K. Firat2 , S. Hascalik3 . Clinic, Yesilyurt State Hospital, Malatya, 2 Department of Radiology, School of Medicine, University of Inonu, Malatya, 3 Department of Obstetrics and Gynecology, School of Medicine, University of Inonu, Malatya, Turkey 1 Anesthesiology
Background: Chronic pelvic pain is a non-malignant pain that is perceived in the structures of female pelvis. It must be continuous or recurrent for at least 6 months. Although pain signals are important factors of the organism’s survival, they have to be down regulated to prevent any severe disturbance of the organism’s function. In this study, effects of acute and chronic noxious stimuli on the diffusional characteristics of female rat brains were investigated. Methods: Ten adult Wistar-albino female rats were imaged with a 1.5 T clinical MR scanner. Hypertonic saline was intraperitoneally given on a daily basis for 15 days as a pain-inciting agent. Diffusion weighted images (DWI) were obtained at prestimulus, and at 1st and 15th day after the initial saline administration and apparent diffusion coefficient (ADC) maps were constructed. Results: Cerebral ADC values were insignificantly decreased at 1st day relative to prestimulus period (p = 0.187). ADC values were significantly increased between the 1st (737±23 mm2 /s × 10−3 ) and the 15th day (837±91 mm2 /s × 10−3 ) to exceed prestimulus values (777±67 mm2 /s × 10−3 ) (p < 0.002). The difference between ADC values of prestimulus period and the 15th day was roughly significant (p = 0.054). Conclusion: These results reflect the presence of transient microstructural alterations that develop during chronic irritation.
208 SIGNS OF ALTERED NOCICEPTION AFTER PROLONGED ADMINISTRATION OF ENDOTHELIN-1 IN RATS K. Deseure1 , G. Hans1,2 ° . 1 Laboratory for Pain Research/University of Antwerp, 2 Multidisciplinary Pain Center/Antwerp University Hospital, Belgium Introduction: Increasing evidence indicates that Endothelin-1 (ET-1) plays a role in peripheral nociceptive signalling. ET-1 is shown to be involved in the pathogenesis of pain states ranging from trauma to cancer. However, until now all behavioural and neurophysiological studies have been based on acute administration of ET-1. We investigated the effects of a more prolonged administration of ET-1 on thermal and mechanical hyperalgesia. Methodology: Sprague-Dawley rats (n = 12) were habituated to the different testing procedures (hot plate testing, von Frey stimulation and pin prick testing) on days −2 and −1. Baseline values were obtained one day before pump implantation (day −1). Rats were subcutaneously implanted with osmotic minipumps that released 22.8mg of ET-1/day. Rats were tested on post-pump days +2, +3, +5, +7, +10 and +17. Results: Rats treated with ET-1 developed thermal hyperalgesia from postoperative day 3 till the end of ET-1 treatment (day +7). This effect gained statistical significance on day +7. Three days after pump removal (day +10), hot plate latencies returned to the normal, preoperative values. ET-1 treated animals also displayed signs of increased sensitivity to both von Frey hair as well as pin prick stimulation of the cutaneous dorsal area where the ET-1 was released into the subcutaneous tissue. Animals also displayed a clinical pattern of increased body shaking on days +2 and +3.
210 ULTRASTRUCTURAL STUDY ABOUT THE NEUROPATHIC PAIN FOLLOWING LUMBAR SPINAL LAMINECTOMY C.Y. Tseng1 , P.Y. Chen1 , C.F. Huang3 , C.H. Chien1 , I.M. Jou2 ° . 1 Department of Anatomy, 2 Department of Orthopedics, National Cheng-Kung University, Tainan, 3 Department of Neurology, Sin-Lau Christian Hospital, Tainan, Taiwan Background & aims: Lumbar laminectomy is a surgical procedure, which is often performed to relieve the serious nerve root compression in chronic low back pain. Unfortunately, continuous pain symptom might be persisting in about 40% patients following this procedure. There are many causes of this pain syndrome and the most common one is epidural fibrosis. Numerous reports suggest that scar fibrosis causes recurrent radicular pain. By our previous animal study, the scar tissue has minimal compression effect under light microscopy, but the scar fibrosis may induce neovascularization and axon swelling in cauda equine after laminectomy in rats. In this study, we first investigated the ultrastructural changes in the nerve roots after laminectomy in rats. Furthermore, immunohistochemistry