Pain
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Comparative Study
Self-medication of a cannabinoid CB2 agonist in an animal model of neuropathic pain.
Drug self-administration methods were used to test the hypothesis that rats would self-medicate with a cannabinoid CB(2) agonist to attenuate a neuropathic pain state. Self-medication of the CB(2) agonist (R,S)-AM1241, but not vehicle, attenuated mechanical hypersensitivity produced by spared nerve injury. Switching rats from (R,S)-AM1241 to vehicle self-administration also decreased lever responding in an extinction paradigm. (R,S)-AM1241 self-administration did not alter paw withdrawal thresholds in sham-operated or naive animals. ⋯ Our results suggest that cannabinoid CB(2) agonists may be exploited to treat neuropathic pain with limited drug abuse liability and central nervous system side effects. These studies validate the use of drug self-administration methods for identifying nonpsychotropic analgesics possessing limited abuse potential. These methods offer potential to elucidate novel analgesics that suppress spontaneous neuropathic pain that is not measured by traditional assessments of evoked pain.
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Comparative Study
Sex differences in perceived pain are affected by an anxious brain.
Decades of research confirm that women have greater pain sensitivity than men. Women also show greater overall anxiety sensitivity than men. Given these differences, we hypothesized that sex differences in anxiety would explain sex differences in experienced pain and physiological responses to pain (at both spinal and cortical levels). ⋯ This means that stable predispositions to respond with heightened apprehension contribute to baseline pain sensitivity differences between the sexes. These results indicate that the modulatory effect of affect on pain-related brain processes may explain why men and women experience painful shocks so differently. In our study, the mediating role of anxiety on sex differences in pain was tested and confirmed using path analysis.
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Comparative Study
Effects of self-discrepancies on activity-related behaviour: explaining disability and quality of life in patients with chronic low back pain.
In chronic low back pain (CLBP) research, the self-discrepancy model has been applied to explain dysfunctional avoidance and persistence behaviour. The main aim of this study was to evaluate whether specific self-discrepancies in patients with CLBP are associated with the abovementioned types of activity-related behaviour and whether changes in self-discrepancies over time are associated with changes in activity-related behaviour. Furthermore, the aim was to evaluate whether avoidance and persistence behaviour are associated with a higher level of disability and a diminished quality of life and whether changes over time in avoidance and persistence behaviour result in changes in disability and quality of life. ⋯ Results indicate that patients with CLBP who feel closer to their ideal-other show more characteristics of persistence behaviour. Patients who move further away from their ideal-own also show more characteristics of persistence behaviour. Furthermore, in patients characterized as avoider, a decrease in a patient's daily uptime was associated with a decrease of mental health-related quality of life.
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Comparative Study
Activation of spinal extracellular signal-regulated kinases (ERK) 1/2 is associated with the development of visceral hyperalgesia of the bladder.
Activation of extracellular signal-regulated kinases (ERK) 1/2 in dorsal horn neurons is important for the development of somatic hypersensitivity and spinal central sensitization after peripheral inflammation. However, data regarding the roles of spinal ERK1/2 in the development of visceral hyperalgesia are sparse. Here we studied the activation of ERK1/2 in the lumbosacral spinal cord after innocuous and noxious distention of the inflamed (cyclophosphamide-treated) and noninflamed urinary bladder in mice. ⋯ Functional blockade of spinal ERK1/2 activity via intrathecal administration of the upstream MEK inhibitor U0126 attenuated distention-evoked bladder nociception and caused a significant downward shift of the VMR stimulus-response curve. In summary, we have provided functional and immunohistochemical evidence that activation of lumbosacral spinal ERK1/2 is associated with the development of primary visceral (bladder) hyperalgesia. Our results suggest that aberrant processing of visceral nociceptive information at the level of the lumbosacral spinal cord via activation of ERK1/2 signaling may contribute to chronic bladder pain in the context of inflammation.