- Email: [email protected]
210 ULTRASTRUCTURAL STUDY ABOUT THE NEUROPATHIC PAIN FOLLOWING LUMBAR SPINAL LAMINECTOMY
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
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European Journal of Pain 2006, Vol 10 (suppl S1)
of protein gene product 9.5 (PGP 9.5), a marker of nerve tissue, was utilized to detect the nerve growth in scar tissue under electron microscopy. Results: Results illustrate that the whirl body and the detachment of plasmalemma could be found in Schwann cells of large myelinated fibers. Neurotubule disruption and neurofilament disorganization also developed in small myelinated or unmyelinated fibers. In addition, numerous nerve fibers labeled by PGP 9.5 were observed in scar tissue on light or electron microscopy after 3 months lumbar laminectomy. These small fibers frequently accompany vessels and spread from periphery to central connective tissue of scar. Conclusions: We conclude that the dysmyelination and axonopathy in roots, and the nerve ingrowth in scar tissue could induce neuropathic pain, which might be the main causes of pain syndrome after spine operation.
211 ESTABLISHMENT OF L5/L6 SPINAL NERVE LIGATION MODEL OF NEUROPATHIC PAIN IN MICE AND PHARMACOLOGICAL CHARACTERIZATION T. Kiso ° , T. Watabiki, M. Tsukamoto, T. Aoki, N. Matsuoka. Pharmacology Research Labs., Drug Discovery Res., Astellas Pharma Inc., Tsukuba, Ibaraki, Japan
Abstracts, 5th EFIC Congress, Free Presentations In CCI model 2 weeks after surgery we did not find significant differences between expolatory or whole day activity of allodynic, sham and naive groups, although a slightly decreased immobility and increased grooming could be observed in the 1st hour. In contrast, general activity of STZtreated group was different from naive group. Decreased locomotor activity and rearing was observed (45%, 61% change) from 1st week and later on. From the 2nd week immobility was decreased by 50% and grooming was increased by 50−60%. These behavioral alterations may reflect the development of illness ( ↓ locomotion) and the experienced pain ( ↑ grooming). While activity of neuropathic rats was not changed in the CCI model, diabetic rats showed considerably different spontaneous activity profile than the naive group. 213 THE CANNABINOID AGONIST WIN 55,212−2 PREVENTS THE DEVELOPMENT OF MECHANICAL ALLODYNIA INDUCED BY CHRONIC CISPLATIN IN THE RAT ´ M.I. Mart´ın ° , G. Vera, A. Chiarlone, P. Cabezos, R. Abalo. Area Farmacolog´ıa, U. Rey Juan Carlos, Alcorc´on, Madrid, Spain
Rodent models of L5/L6 spinal nerve ligation (SNL) induce behavioral signs similar to the symptoms of neuropathic pain in humans. The pharmacological characterization of L5/L6 SNL has been done using rat models almost exclusively; however, there have been a few using mice. In this study, we established a mouse model of L5/L6 SNL, and also examined the effects of known antinociceptive drugs on mechanical allodynia in the model. Either the tight ligation of the L5 and L6 spinal nerves or a sham operation was performed on male ICR mice. The paw withdrawal threshold was measured in response to mechanical stimulation with von Frey hairs. Mechanical allodynia in the ipsilateral side paw was observed from days 1 to 28 after surgery. The effects of drugs were evaluated 7−14 days after surgery. Mexiletine (10, 30 and 100 mg/kg p.o.) dose-dependently increased the paw withdrawal threshold. It completely reversed the threshold at 100 mg/kg, but also caused sedation or motor impairment. Gabapentin (100 and 300 mg/kg p.o.) completely reversed the paw withdrawal threshold, but also caused a decrease in locomotor activity. Morphine (1, 3 and 5 mg/kg s.c.) caused a partial recovery of the paw withdrawal threshold, with the maximum effect at 3 mg/kg. This mouse model of L5/L6 SNL results in significant mechanical allodynia, which is a pharmacological response similar to that reported for rats. Therefore, this model will be very useful for the investigation of the effects of novel antinociceptive compounds and the mechanisms of neuropathic pain.
Background and Aims: Recently, we have shown that the synthetic cannabinoid agonist WIN 55,212−2 (WIN) is able to revert allodynia and hyperalgesia induced by chronic paclitaxel (Pain 2005, 118: 23−34). Since cannabinoids exert neuroprotective effects in the central nervous system, the peripheral nervous system could also be protected by these drugs if given prophylactically. Therefore, the aim of the present work was to study whether or not cannabinoids could prevent the development of neuropathic pain induced by antineoplastic drugs. Methods: For 5 consecutive weeks, on each Monday, male Wistar rats received two injections: 1- saline/WIN (0.5−2 mg/kg)/vehicle of WIN; 2saline/cisplatin (1−3 mg/kg). The following parameters were measured: from Monday to Friday, temperature, body weight and food ingestion; on each Tuesday, spontaneous locomotor activity; on each Friday (4 days after treatment), the threshold for mechanical allodynia (von Frey filaments). Results: Treatment with WIN (up to 2 mg/kg) or its vehicle had no effect in the parameters measured. Temperature or spontaneous locomotor activity remained unaltered regardless of the treatment. Cisplatin induced both a reduction in body weight and food ingestion and an intense decrease in the threshold for mechanical allodynia. Although anorexia was not significantly prevented by WIN, this cannabinoid agonist completely avoided the development of mechanical allodynia. Conclusions: Cannabinoids could protect the peripheral nervous system against neuropathy induced by antitumoral drugs. They could be useful as a prophylactic means to avoid pain induced by chemotherapy. Acknowledgements: Supported by Ministerio de Educaci´on y Ciencia (SAF 2003–08003-C02−01).
212 SPONTANEOUS ACTIVITY AND BEHAVIOUR PATTERN OF RATS IN ANIMAL MODELS OF NERVE INJURY TYPE AND DIABETIC NEUROPATHY
214 GENE EXPRESSION ANALYSIS OF DIFFERENT PROTEIN KINASE C ISOZYMES IN METABOLIC AND TRAUMATIC ANIMAL MODELS OF PAINFUL PERIPHERAL NEUROPATHY
K.S. Kord´as ° , L. Felm´erai-Horv´ath, K. Galg´oczy, C. Horv´ath. Neuropharmacology Dept, Gedeon Richter Ltd./Budapest, Hungary
M. Mattioli1 ° , C. Gattuso1 , G. De Siena2 , P. Tarroni1 . 1 AXXAM s.r.l., San Raffaele Biomedical Science Park, Milan, 2 Department of Critical Care Medicine and Surgery, University of Florence, Florence, Italy
Chronic constriction injury (CCI) and streptozotocine (STZ) induced diabetic neuropathy (DNP) are often applied models to examine chronic pain in rats. Since very little is known about general activity of animals our goal was to investigate the behavioral patterns of rats in these pain models. In the CCI model, rats with mechanical allodynia measured with von Frey hairs were included in the study with parallel sham operated and naive groups. From STZ-treated rats those with blood glucose level higher than 14 mM were compared to age-matched naive controls once a week. General activity was recorded using the automated LABORAS™ system. The time spent by locomotion, immobility, rearing and grooming was registered in parallel groups for one hour in DNP and for 24 hours in CCI model.
Background and Aims: Comparative gene expression studies in different animal models represent an important resource for a better understanding of the molecular mechanisms underlying different pain states. The aim of our study was to investigate the expression modulation of the epsilon and gamma isozymes of the Protein Kinase C following neuropathic pain development. Methods: qPCR was used to detect changes in the mRNA expression of two PKC isoforms (Prkce and Prkcc) in three rat models of painful peripheral neuropathy. The mRNA quantitative analysis has been conducted through a comprehensive set of nervous tissues from chronic constriction injury of the sciatic nerve (CCI), sciatic nerve axotomy and streptozotocin (STZ)-induced diabetes animal models.
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
S58
European Journal of Pain 2006, Vol 10 (suppl S1)
of protein gene product 9.5 (PGP 9.5), a marker of nerve tissue, was utilized to detect the nerve growth in scar tissue under electron microscopy. Results: Results illustrate that the whirl body and the detachment of plasmalemma could be found in Schwann cells of large myelinated fibers. Neurotubule disruption and neurofilament disorganization also developed in small myelinated or unmyelinated fibers. In addition, numerous nerve fibers labeled by PGP 9.5 were observed in scar tissue on light or electron microscopy after 3 months lumbar laminectomy. These small fibers frequently accompany vessels and spread from periphery to central connective tissue of scar. Conclusions: We conclude that the dysmyelination and axonopathy in roots, and the nerve ingrowth in scar tissue could induce neuropathic pain, which might be the main causes of pain syndrome after spine operation.
211 ESTABLISHMENT OF L5/L6 SPINAL NERVE LIGATION MODEL OF NEUROPATHIC PAIN IN MICE AND PHARMACOLOGICAL CHARACTERIZATION T. Kiso ° , T. Watabiki, M. Tsukamoto, T. Aoki, N. Matsuoka. Pharmacology Research Labs., Drug Discovery Res., Astellas Pharma Inc., Tsukuba, Ibaraki, Japan
Abstracts, 5th EFIC Congress, Free Presentations In CCI model 2 weeks after surgery we did not find significant differences between expolatory or whole day activity of allodynic, sham and naive groups, although a slightly decreased immobility and increased grooming could be observed in the 1st hour. In contrast, general activity of STZtreated group was different from naive group. Decreased locomotor activity and rearing was observed (45%, 61% change) from 1st week and later on. From the 2nd week immobility was decreased by 50% and grooming was increased by 50−60%. These behavioral alterations may reflect the development of illness ( ↓ locomotion) and the experienced pain ( ↑ grooming). While activity of neuropathic rats was not changed in the CCI model, diabetic rats showed considerably different spontaneous activity profile than the naive group. 213 THE CANNABINOID AGONIST WIN 55,212−2 PREVENTS THE DEVELOPMENT OF MECHANICAL ALLODYNIA INDUCED BY CHRONIC CISPLATIN IN THE RAT ´ M.I. Mart´ın ° , G. Vera, A. Chiarlone, P. Cabezos, R. Abalo. Area Farmacolog´ıa, U. Rey Juan Carlos, Alcorc´on, Madrid, Spain
Rodent models of L5/L6 spinal nerve ligation (SNL) induce behavioral signs similar to the symptoms of neuropathic pain in humans. The pharmacological characterization of L5/L6 SNL has been done using rat models almost exclusively; however, there have been a few using mice. In this study, we established a mouse model of L5/L6 SNL, and also examined the effects of known antinociceptive drugs on mechanical allodynia in the model. Either the tight ligation of the L5 and L6 spinal nerves or a sham operation was performed on male ICR mice. The paw withdrawal threshold was measured in response to mechanical stimulation with von Frey hairs. Mechanical allodynia in the ipsilateral side paw was observed from days 1 to 28 after surgery. The effects of drugs were evaluated 7−14 days after surgery. Mexiletine (10, 30 and 100 mg/kg p.o.) dose-dependently increased the paw withdrawal threshold. It completely reversed the threshold at 100 mg/kg, but also caused sedation or motor impairment. Gabapentin (100 and 300 mg/kg p.o.) completely reversed the paw withdrawal threshold, but also caused a decrease in locomotor activity. Morphine (1, 3 and 5 mg/kg s.c.) caused a partial recovery of the paw withdrawal threshold, with the maximum effect at 3 mg/kg. This mouse model of L5/L6 SNL results in significant mechanical allodynia, which is a pharmacological response similar to that reported for rats. Therefore, this model will be very useful for the investigation of the effects of novel antinociceptive compounds and the mechanisms of neuropathic pain.
Background and Aims: Recently, we have shown that the synthetic cannabinoid agonist WIN 55,212−2 (WIN) is able to revert allodynia and hyperalgesia induced by chronic paclitaxel (Pain 2005, 118: 23−34). Since cannabinoids exert neuroprotective effects in the central nervous system, the peripheral nervous system could also be protected by these drugs if given prophylactically. Therefore, the aim of the present work was to study whether or not cannabinoids could prevent the development of neuropathic pain induced by antineoplastic drugs. Methods: For 5 consecutive weeks, on each Monday, male Wistar rats received two injections: 1- saline/WIN (0.5−2 mg/kg)/vehicle of WIN; 2saline/cisplatin (1−3 mg/kg). The following parameters were measured: from Monday to Friday, temperature, body weight and food ingestion; on each Tuesday, spontaneous locomotor activity; on each Friday (4 days after treatment), the threshold for mechanical allodynia (von Frey filaments). Results: Treatment with WIN (up to 2 mg/kg) or its vehicle had no effect in the parameters measured. Temperature or spontaneous locomotor activity remained unaltered regardless of the treatment. Cisplatin induced both a reduction in body weight and food ingestion and an intense decrease in the threshold for mechanical allodynia. Although anorexia was not significantly prevented by WIN, this cannabinoid agonist completely avoided the development of mechanical allodynia. Conclusions: Cannabinoids could protect the peripheral nervous system against neuropathy induced by antitumoral drugs. They could be useful as a prophylactic means to avoid pain induced by chemotherapy. Acknowledgements: Supported by Ministerio de Educaci´on y Ciencia (SAF 2003–08003-C02−01).
212 SPONTANEOUS ACTIVITY AND BEHAVIOUR PATTERN OF RATS IN ANIMAL MODELS OF NERVE INJURY TYPE AND DIABETIC NEUROPATHY
214 GENE EXPRESSION ANALYSIS OF DIFFERENT PROTEIN KINASE C ISOZYMES IN METABOLIC AND TRAUMATIC ANIMAL MODELS OF PAINFUL PERIPHERAL NEUROPATHY
K.S. Kord´as ° , L. Felm´erai-Horv´ath, K. Galg´oczy, C. Horv´ath. Neuropharmacology Dept, Gedeon Richter Ltd./Budapest, Hungary
M. Mattioli1 ° , C. Gattuso1 , G. De Siena2 , P. Tarroni1 . 1 AXXAM s.r.l., San Raffaele Biomedical Science Park, Milan, 2 Department of Critical Care Medicine and Surgery, University of Florence, Florence, Italy
Chronic constriction injury (CCI) and streptozotocine (STZ) induced diabetic neuropathy (DNP) are often applied models to examine chronic pain in rats. Since very little is known about general activity of animals our goal was to investigate the behavioral patterns of rats in these pain models. In the CCI model, rats with mechanical allodynia measured with von Frey hairs were included in the study with parallel sham operated and naive groups. From STZ-treated rats those with blood glucose level higher than 14 mM were compared to age-matched naive controls once a week. General activity was recorded using the automated LABORAS™ system. The time spent by locomotion, immobility, rearing and grooming was registered in parallel groups for one hour in DNP and for 24 hours in CCI model.
Background and Aims: Comparative gene expression studies in different animal models represent an important resource for a better understanding of the molecular mechanisms underlying different pain states. The aim of our study was to investigate the expression modulation of the epsilon and gamma isozymes of the Protein Kinase C following neuropathic pain development. Methods: qPCR was used to detect changes in the mRNA expression of two PKC isoforms (Prkce and Prkcc) in three rat models of painful peripheral neuropathy. The mRNA quantitative analysis has been conducted through a comprehensive set of nervous tissues from chronic constriction injury of the sciatic nerve (CCI), sciatic nerve axotomy and streptozotocin (STZ)-induced diabetes animal models.