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Attenuation of tactile allodynia in a rat model of neuropathic pain
Abstracts
e39
135
dose levels of 100 mg/kg displayed no significant difference from the control.
Pain assessment in monosodium iodoacetate (MIA)-induced osteoarthritis (OA) model Rana Samadfam, Luc Chouinard, Kevin Norton, Susan Smith
doi:10.1016/j.vascn.2013.01.142
Charles River Laboratories, Montreal, QC, Canada
137
Major findings in the basic science of pain have failed to bring new drugs into clinical practice, partly due to the fact that the preclinical models used for pain assessments do not adequately represent the clinical condition. A potential approach to evaluate antinociceptives is using animal models with diseases e.g. OA. The objectives of this study were to determine the dose of MIA to induce joint discomfort and assess pain endpoints. Adult rats received an intra-articular injection of saline or MIA at 1 or 3 mg/dose. Baseline allodynia was evaluated on Day 14 using: body position, gait, tactile allodynia (VFF) and dynamic weight bearing (DWB). Animals dosed with 1 mg/dose generally had less severe OA symptoms with normal body position and gait and only trends of an altered weight bearing of the right rear paw compared to controls. Animals treated with 3 mg/dose had more severe OA had normal gait and clearly showed signs of joint discomfort (right rear paw) as measured by DWB. Animals with severe symptoms of OA were treated with Naproxen and pain was evaluated at 4 and 6 h post dose. Naproxen reduced pain in the majority of the 3 mg/dose animals as evidenced by balanced weight distribution and comparable use of both rear paws. These results indicate that reflexive pain measures were successfully measured at 1 mg/dose. However, the 3 mg/dose produced consistent quantitative changes and was considered the optimal dose of MIA to assess pain.
Early iron deficiency and attentional deficits from basic science to treatment Wael Mohamed
doi:10.1016/j.vascn.2013.01.141
136 Attenuation of tactile allodynia in a rat model of neuropathic pain Giuseppina Iacono, Kevin Norton Charles River Laboratories, Montreal, QC, Canada Neuropathic pain is defined as pain initiated or caused by a primary lesion or dysfunction in the nervous system and is an area of largely unmet therapeutic need, with reports indicating that b50% of patients suffering from neuropathic pain achieve relief with any single therapy. Spinal nerve ligation (SNL) models has been proposed as a suitable method for inducing neuropathic pain, with reports suggesting that this model induces a higher degree of tactile allodynia than other neuropathic pain models e.g. chronic constriction injury and partial sciatic nerve ligation. Baseline tactile sensitivity, on the left hind paw, was assessed in male Sprague–Dawley rats using standard Von Frey filaments and animals displaying a threshold of b15 g were excluded. Animals underwent surgery to unilaterally ligate the L5 and L6 spinal nerves, with the exception of a surgical sham group. Two weeks following the surgical procedure, rats were assessed for postsurgery thresholds and animals displaying a hind paw withdrawal threshold b4.0 g were considered as displaying tactile allodynia and assigned to vehicle and treated groups. Animals were treated with vehicle, WIN55,212-2 (1, 2 and 4 mg/kg) or gabapentin (100, 300 and 900 mg/kg). Win 55,212-2 resulted in a dose dependent increase in the pain threshold of the affected paw to tactile allodynia at dose levels of 1, 2 and 4 mg/kg. Whilst Gabapentin appeared to be effective at dose levels of 300 and 900 mg/kg, in attenuating allodynia, however
Menoufiya Medical School, Menoufiya, Egypt Introduction: A number of investigators have shown that in humans, the most salient deleterious effect of iron deficiency (ID) early in life is persistent cognitive impairment. Objectives: The aim of this work was to test the hypothesis that rats made iron deficient in early infancy exhibit cognitive deficits similar to those seen in humans at adolescence. A second aim was to investigate whether the deficit could be treated pharmacologically. Methods: Sprague–Dawley rats were made iron deficient (ID) starting at postnatal day 4 by being placed with iron-deficient dams (vs. control). At weaning, all pups were placed on an iron-sufficient diet for the remainder of the study. At 45 days of age, the animals were tested for attention set shifting. After testing, the animals were assigned to one of three methylphenidate (MePh) dose groups, 1, 5 or 10 mg/kg, p.o., vs. vehicle control and treated daily for 15 days prior to a second round of attention set shift testing and continued throughout testing. Results: The results showed that ID rats performed more poorly than controls overall on attention set-shift testing. MePh improved ID rats' performance and lower doses were more effective than higher doses. Conclusions: This is the first demonstration that MePh can improve cognitive deficits produced by early ID in animals. These findings may open the possibility of pharmacotherapy to treat the persistent cognitive difficulties in children who were severely iron deficient in early infancy.
doi:10.1016/j.vascn.2013.01.143
138 Acute anesthetized measurements of right ventricular and pulmonary artery pressure in a rat model of pulmonary artery hypertension Dezhi Xing, Rodney Smith, James Hennan, Paul Levesque Bristol-Myers Squibb, Pennington, NJ, USA Pulmonary artery hypertension (PAH) is a serious illness that affects both the lungs and the right side of the heart. PAH is a difficult safety signal to assess in preclinical models and clinical trials, but it has been linked to drug administration in certain therapies such as kinase inhibitors for oncology. The aim of this study was to establish a rat PAH model with assessment of right ventricular pressure (RVP) and pulmonary artery (PAP). Male, SD rats received either vehicle (3 ml/kg, n = 4) or monocrotaline (70 mg/kg, n = 4) or (80 mg/kg, n = 4). Five weeks after dosing, rats were anesthetized with ketamine (25 mg/kg) and xylazine (15 mg/kg). An endotracheal tube was inserted into the trachea and connected to respirator to control respiration. After opening the chest, a 2 F Millar catheter was
e39
135
dose levels of 100 mg/kg displayed no significant difference from the control.
Pain assessment in monosodium iodoacetate (MIA)-induced osteoarthritis (OA) model Rana Samadfam, Luc Chouinard, Kevin Norton, Susan Smith
doi:10.1016/j.vascn.2013.01.142
Charles River Laboratories, Montreal, QC, Canada
137
Major findings in the basic science of pain have failed to bring new drugs into clinical practice, partly due to the fact that the preclinical models used for pain assessments do not adequately represent the clinical condition. A potential approach to evaluate antinociceptives is using animal models with diseases e.g. OA. The objectives of this study were to determine the dose of MIA to induce joint discomfort and assess pain endpoints. Adult rats received an intra-articular injection of saline or MIA at 1 or 3 mg/dose. Baseline allodynia was evaluated on Day 14 using: body position, gait, tactile allodynia (VFF) and dynamic weight bearing (DWB). Animals dosed with 1 mg/dose generally had less severe OA symptoms with normal body position and gait and only trends of an altered weight bearing of the right rear paw compared to controls. Animals treated with 3 mg/dose had more severe OA had normal gait and clearly showed signs of joint discomfort (right rear paw) as measured by DWB. Animals with severe symptoms of OA were treated with Naproxen and pain was evaluated at 4 and 6 h post dose. Naproxen reduced pain in the majority of the 3 mg/dose animals as evidenced by balanced weight distribution and comparable use of both rear paws. These results indicate that reflexive pain measures were successfully measured at 1 mg/dose. However, the 3 mg/dose produced consistent quantitative changes and was considered the optimal dose of MIA to assess pain.
Early iron deficiency and attentional deficits from basic science to treatment Wael Mohamed
doi:10.1016/j.vascn.2013.01.141
136 Attenuation of tactile allodynia in a rat model of neuropathic pain Giuseppina Iacono, Kevin Norton Charles River Laboratories, Montreal, QC, Canada Neuropathic pain is defined as pain initiated or caused by a primary lesion or dysfunction in the nervous system and is an area of largely unmet therapeutic need, with reports indicating that b50% of patients suffering from neuropathic pain achieve relief with any single therapy. Spinal nerve ligation (SNL) models has been proposed as a suitable method for inducing neuropathic pain, with reports suggesting that this model induces a higher degree of tactile allodynia than other neuropathic pain models e.g. chronic constriction injury and partial sciatic nerve ligation. Baseline tactile sensitivity, on the left hind paw, was assessed in male Sprague–Dawley rats using standard Von Frey filaments and animals displaying a threshold of b15 g were excluded. Animals underwent surgery to unilaterally ligate the L5 and L6 spinal nerves, with the exception of a surgical sham group. Two weeks following the surgical procedure, rats were assessed for postsurgery thresholds and animals displaying a hind paw withdrawal threshold b4.0 g were considered as displaying tactile allodynia and assigned to vehicle and treated groups. Animals were treated with vehicle, WIN55,212-2 (1, 2 and 4 mg/kg) or gabapentin (100, 300 and 900 mg/kg). Win 55,212-2 resulted in a dose dependent increase in the pain threshold of the affected paw to tactile allodynia at dose levels of 1, 2 and 4 mg/kg. Whilst Gabapentin appeared to be effective at dose levels of 300 and 900 mg/kg, in attenuating allodynia, however
Menoufiya Medical School, Menoufiya, Egypt Introduction: A number of investigators have shown that in humans, the most salient deleterious effect of iron deficiency (ID) early in life is persistent cognitive impairment. Objectives: The aim of this work was to test the hypothesis that rats made iron deficient in early infancy exhibit cognitive deficits similar to those seen in humans at adolescence. A second aim was to investigate whether the deficit could be treated pharmacologically. Methods: Sprague–Dawley rats were made iron deficient (ID) starting at postnatal day 4 by being placed with iron-deficient dams (vs. control). At weaning, all pups were placed on an iron-sufficient diet for the remainder of the study. At 45 days of age, the animals were tested for attention set shifting. After testing, the animals were assigned to one of three methylphenidate (MePh) dose groups, 1, 5 or 10 mg/kg, p.o., vs. vehicle control and treated daily for 15 days prior to a second round of attention set shift testing and continued throughout testing. Results: The results showed that ID rats performed more poorly than controls overall on attention set-shift testing. MePh improved ID rats' performance and lower doses were more effective than higher doses. Conclusions: This is the first demonstration that MePh can improve cognitive deficits produced by early ID in animals. These findings may open the possibility of pharmacotherapy to treat the persistent cognitive difficulties in children who were severely iron deficient in early infancy.
doi:10.1016/j.vascn.2013.01.143
138 Acute anesthetized measurements of right ventricular and pulmonary artery pressure in a rat model of pulmonary artery hypertension Dezhi Xing, Rodney Smith, James Hennan, Paul Levesque Bristol-Myers Squibb, Pennington, NJ, USA Pulmonary artery hypertension (PAH) is a serious illness that affects both the lungs and the right side of the heart. PAH is a difficult safety signal to assess in preclinical models and clinical trials, but it has been linked to drug administration in certain therapies such as kinase inhibitors for oncology. The aim of this study was to establish a rat PAH model with assessment of right ventricular pressure (RVP) and pulmonary artery (PAP). Male, SD rats received either vehicle (3 ml/kg, n = 4) or monocrotaline (70 mg/kg, n = 4) or (80 mg/kg, n = 4). Five weeks after dosing, rats were anesthetized with ketamine (25 mg/kg) and xylazine (15 mg/kg). An endotracheal tube was inserted into the trachea and connected to respirator to control respiration. After opening the chest, a 2 F Millar catheter was