Objective: Individual differences in the sensitivity to pain and the factors that may contribute to these differences are well studied. Nevertheless, there is no single test that can reliably classify subjects as bein...Objective: Individual differences in the sensitivity to pain and the factors that may contribute to these differences are well studied. Nevertheless, there is no single test that can reliably classify subjects as being sensitive or insensitive to pain. Methods: In the present study, hierarchical clustering and K-means cluster analysis was used to identify subgroups among 191 healthy subjects (105 females, 86 males) according to their sensitivity to pain. Group determination was based on the subjects’ response to experimental noxious stimuli of heat (pain intensity), cold (cold pain threshold, tolerance, and intensity), and conditioned pain modulation (CPM, tested by co-administering repeated short painful heat stimuli and a conditioning tonic cold pain stimulation). In addition, in order to determine if the subjects in these subgroups differed on personality traits scores on Cloninger’s Tridimensional Personality Questionnaire (TPQ, outcome measure) for the three dimensions of personality: Novelty Seeking (NS);Harm Avoidance (HA);and Reward Dependence (RD) were calculated. Results: Based on pain scores, subjects were grouped as low pain (57%) with a low level of sensitivity in pain parameters, or high pain (43%) cluster members. The high pain had significant higher scores of HA (p = 0.05) and RD (p = 0.05) than the low pain group. Conclusions: This method of sub-grouping may be useful for identifying the mechanisms underlying individual variability in the sensitivity to pain and may point to groups at risk for experiencing high levels of clinical pain.展开更多
Increased reactive oxygen species by the activation of NADPH oxidase（NOX） contributes to the development of diabetic complications.Apocynin,a NOX inhibitor,increases sciatic nerve conductance and blood flow in diabe...Increased reactive oxygen species by the activation of NADPH oxidase（NOX） contributes to the development of diabetic complications.Apocynin,a NOX inhibitor,increases sciatic nerve conductance and blood flow in diabetic rats.We investigated potential protective effect of apocynin in rat diabetic neuropathy and its precise mechanism of action at molecular level.Rat models of streptozotocin-induced diabetes were treated with apocynin（30 and 100 mg/kg per day,intragastrically） for 4 weeks.Mechanical hyperalgesia and allodynia were determined weekly using analgesimeter and dynamic plantar aesthesiometer.Western blot analysis and histochemistry/immunohistochemistry were performed in the lumbar spinal cord and sciatic nerve respectively.Streptozotocin injection reduced pain threshold in analgesimeter,but not in aesthesiometer.Apocynin treatment increased pain threshold dose-dependently.Western blot analysis showed an increase in catalase and NOX-p47 phox protein expression in the spinal cord.However,protein expressions of neuronal and inducible nitric oxide synthase（n NOS,i NOS）,superoxide dismutase,glutathion peroxidase,nitrotyrosine,tumor necrosis factor-α,interleukin-6,interleukin-1β,aldose reductase,cyclooxygenase-2 or MAC-1（marker for increased microgliosis） in the spinal cord remained unchanged.Western blot analysis results also demonstrated that apocynin decreased NOX-p47 phox expression at both doses and catalase expression at 100 mg/kg per day.Histochemistry of diabetic sciatic nerve revealed marked degeneration.n NOS and i NOS immunoreactivities were increased,while S-100 immunoreactivity（Schwann cell marker） was decreased in sciatic nerve.Apocynin treatment reversed these changes dose-dependently.In conclusion,decreased pain threshold of diabetic rats was accompanied by increased NOX and catalase expression in the spinal cord and increased degeneration in the sciatic nerve characterized by increased NOS expression and Schwann cell loss.Apocynin treatment attenuates neuropathic pain by decelerating the increased oxidative stress-mediated pathogenesis in diabetic rats.展开更多
文摘Objective: Individual differences in the sensitivity to pain and the factors that may contribute to these differences are well studied. Nevertheless, there is no single test that can reliably classify subjects as being sensitive or insensitive to pain. Methods: In the present study, hierarchical clustering and K-means cluster analysis was used to identify subgroups among 191 healthy subjects (105 females, 86 males) according to their sensitivity to pain. Group determination was based on the subjects’ response to experimental noxious stimuli of heat (pain intensity), cold (cold pain threshold, tolerance, and intensity), and conditioned pain modulation (CPM, tested by co-administering repeated short painful heat stimuli and a conditioning tonic cold pain stimulation). In addition, in order to determine if the subjects in these subgroups differed on personality traits scores on Cloninger’s Tridimensional Personality Questionnaire (TPQ, outcome measure) for the three dimensions of personality: Novelty Seeking (NS);Harm Avoidance (HA);and Reward Dependence (RD) were calculated. Results: Based on pain scores, subjects were grouped as low pain (57%) with a low level of sensitivity in pain parameters, or high pain (43%) cluster members. The high pain had significant higher scores of HA (p = 0.05) and RD (p = 0.05) than the low pain group. Conclusions: This method of sub-grouping may be useful for identifying the mechanisms underlying individual variability in the sensitivity to pain and may point to groups at risk for experiencing high levels of clinical pain.
基金supported by the Research Fund of Ege University(Project No.2010-TIP-076)
文摘Increased reactive oxygen species by the activation of NADPH oxidase（NOX） contributes to the development of diabetic complications.Apocynin,a NOX inhibitor,increases sciatic nerve conductance and blood flow in diabetic rats.We investigated potential protective effect of apocynin in rat diabetic neuropathy and its precise mechanism of action at molecular level.Rat models of streptozotocin-induced diabetes were treated with apocynin（30 and 100 mg/kg per day,intragastrically） for 4 weeks.Mechanical hyperalgesia and allodynia were determined weekly using analgesimeter and dynamic plantar aesthesiometer.Western blot analysis and histochemistry/immunohistochemistry were performed in the lumbar spinal cord and sciatic nerve respectively.Streptozotocin injection reduced pain threshold in analgesimeter,but not in aesthesiometer.Apocynin treatment increased pain threshold dose-dependently.Western blot analysis showed an increase in catalase and NOX-p47 phox protein expression in the spinal cord.However,protein expressions of neuronal and inducible nitric oxide synthase（n NOS,i NOS）,superoxide dismutase,glutathion peroxidase,nitrotyrosine,tumor necrosis factor-α,interleukin-6,interleukin-1β,aldose reductase,cyclooxygenase-2 or MAC-1（marker for increased microgliosis） in the spinal cord remained unchanged.Western blot analysis results also demonstrated that apocynin decreased NOX-p47 phox expression at both doses and catalase expression at 100 mg/kg per day.Histochemistry of diabetic sciatic nerve revealed marked degeneration.n NOS and i NOS immunoreactivities were increased,while S-100 immunoreactivity（Schwann cell marker） was decreased in sciatic nerve.Apocynin treatment reversed these changes dose-dependently.In conclusion,decreased pain threshold of diabetic rats was accompanied by increased NOX and catalase expression in the spinal cord and increased degeneration in the sciatic nerve characterized by increased NOS expression and Schwann cell loss.Apocynin treatment attenuates neuropathic pain by decelerating the increased oxidative stress-mediated pathogenesis in diabetic rats.
