Pain
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Our previous work indicates that the intrathecal administration of neuropeptide Y (NPY) acts at its cognate receptors to reduce behavioral signs of nociception in several models of inflammatory pain, including the formalin test. The present study extends these findings to a rat model of peripheral neuropathic pain, and then evaluates the hypothesis that NPY inhibits inflammation- and nerve injury-induced activation of spinal nociceptive transmission. Here we show that NPY dose-dependently reduced behavioral signs of mechanical and cold hypersensitivity in the spared nerve injury (SNI) model. ⋯ We found that intrathecal NPY reduced both formalin- and SNI-induced Fos expression. NPY inhibition of SNI-induced Fos expression was localized to the sural (uninjured) innervation territory, and could be blocked by intrathecal BIBO3304 and BIIE0246. We conclude that NPY acts at spinal Y1 and Y2 receptors to reduce spinal neuron activity and behavioral signs of inflammatory or neuropathic pain.
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Comparative Study
Selective stimulation of GalR1 and GalR2 in rat substantia gelatinosa reveals a cellular basis for the anti- and pro-nociceptive actions of galanin.
Galanin modulates spinal nociceptive processing by interacting with two receptors, GalR1 and GalR2. The underlying neurophysiological mechanisms were examined by whole-cell recording from identified neurons in the substantia gelatinosa of young adult rats. GalR1 was activated with a 'cocktail' containing the GalR1/2 agonist, AR-M 961 (0.5 microM), in the presence of the GalR2 antagonist, M871 (1.0-2.5 microM). ⋯ GalR2 was also located presynaptically, as AR-M 1896 increased the interevent interval of spontaneous EPSCs in both delay and tonic cells. By contrast, the 'GalR1 agonist cocktail' had little effect on spontaneous EPSCs, suggesting that presynaptic terminals do not express GalR1. These diverse actions of GalR1 and GalR2 activation on both inhibitory and excitatory neurons are discussed in relation to the known spinal antinociceptive and pro-nociceptive actions of galanin, to the possible association of GalR1 with the inhibitory G-protein, G(i/o) and to report that GalR2 activation suppresses Ca2+ channel currents.
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Pain is common in patients with multiple sclerosis (MS), but estimates of its prevalence have varied widely. The literature describing pain in MS patients spans four decades and has employed a range of different methodologies. We undertook a systematic review in order to summarize current understanding of the association between MS and pain and provide a basis for the design and interpretation of future studies. ⋯ Putative mechanisms of pain in patients with MS are discussed, and a classification of pain in MS is proposed. Few randomized clinical trials of treatments for MS pain have been conducted, and the limitations of current knowledge regarding approaches for treating MS pain are discussed. Suggestions for future studies that would increase understanding of the natural history, mechanisms, and treatment of pain in patients with MS are presented.
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Multicenter Study Comparative Study
Neurophysiological characterization of postherniotomy pain.
Inguinal herniotomy is one of the most frequent surgical procedures and chronic pain affecting everyday activities is reported in approximately 10% of patients. However, the neurophysiological changes and underlying pathophysiological mechanisms of postherniotomy pain are not known in detail, thereby precluding advances in treatment strategies and prophylaxis. Therefore, we examined forty-six patients reporting moderate to severe postherniotomy pain affecting daily activities for more than a year postoperatively, and compared them with a control group of patients without pain 1 yr postoperatively. ⋯ The specific finding of reduced pain detection threshold over the external inguinal annulus is consistent with damage to the cutaneous innervation territory of nervous structures in the inguinal region. The correspondence between pain location and sensory disturbance suggests that the pain is neuropathic in nature. Whether the underlying pathophysiological mechanisms are related to direct intraoperative nerve injury or nerve injury due to an inflammatory mesh response remains to be determined.
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Comparative Study
Exposure to movement in chronic back pain: evidence of successful generalization across a reaching task.
According to the fear-avoidance model, kinesiophobia (pain-related fear) is an important factor in the development of chronic pain and disability through the maintenance of maladaptive avoidance behaviors. Using a paradigm that required repeated exposure to a reaching task, the current study investigated generalization of pain and harm expectancy corrections (i.e., the tendency to bring expectations in line with experience) in chronic low back pain sufferers with high versus low levels of kinesiophobia. Sixty participants were asked to consecutively perform four adaptations of a reaching task, each introducing an element of increased intensity. ⋯ Further, highly kinesiophobic female, but not male, participants demonstrated greater overprediction of harm relative to low kinesiophobic counterparts during the first reaching trial. Finally, in contrast to previous investigations, highly kinesiophobic participants showed successful generalization of pain expectancy corrections across movement tasks. Possible clinical implications of the findings are noted.