Pain
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Chronic musculoskeletal conditions are increasingly conceived as involving altered central nervous system processing, and impaired nociceptive flexor reflex (NFR) appears to reflect altered central nervous system processing. The primary objective was to synthesize the evidence for impaired NFR in these conditions. The secondary objective was to evaluate the NFR stimuli parameters employed by reviewed studies. ⋯ The results indicate that there is evidence of central hyperexcitability in people with chronic musculoskeletal pain. Our review also suggests that shorter inter-pulse duration tends to yield smaller variability in NFR threshold. However, further research investigating optimal stimulation parameters is still warranted.
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Tissue injury during a critical period of early life can facilitate spontaneous glutamatergic transmission within developing pain circuits in the superficial dorsal horn (SDH) of the spinal cord. However, the extent to which neonatal tissue damage strengthens nociceptive synaptic input to specific subpopulations of SDH neurons, as well as the mechanisms underlying this distinct form of synaptic plasticity, remains unclear. Here we use in vitro whole-cell patch clamp recordings from rodent spinal cord slices to demonstrate that neonatal surgical injury selectively potentiates high-threshold primary afferent input to immature lamina II neurons. ⋯ This occurs in a widespread manner within the developing SDH, as incision elevated miniature excitatory postsynaptic current frequency in both GABAergic and presumed glutamatergic lamina II neurons of Gad-GFP transgenic mice. The administration of exogenous nerve growth factor into the rat hindpaw mimicked the effects of early tissue damage on excitatory synaptic function, while blocking trkA receptors in vivo abolished the changes in both spontaneous and primary afferent-evoked glutamatergic transmission following incision. These findings illustrate that neonatal tissue damage can alter the gain of developing pain pathways by activating nerve growth factor-dependent signaling cascades, which modify synaptic efficacy at the first site of nociceptive processing within the central nervous system.
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The purinergic P2X7 receptor is implicated in both neuropathic and inflammatory pain, and has been suggested as a possible target in pain treatment. However, the specific role of the P2X7 receptor in bone cancer pain is unknown. We demonstrated that BALB/cJ P2X7 receptor knockout (P2X7R KO) mice were susceptible to bone cancer pain and moreover had an earlier onset of pain-related behaviours compared with cancer-bearing, wild-type mice. ⋯ However, the recent discovery of a P2X7 receptor splice variant expressed in the knockout mice used for this study complicates the interpretation of the results. The P2X7 splice variant receptor was detected in the spinal cord but not in osteoclasts of the P2X7R KO mouse. Further experiments are needed to elucidate the exact role of the P2X7 receptors in bone cancer pain.
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Randomized Controlled Trial Multicenter Study
Patterns of sickness absence a decade after pain-related multidisciplinary rehabilitation.
Multidisciplinary programmes using a vocational approach can enhance work return in chronic pain patients, but little is known about the long-term effects of rehabilitation. The current study examined the patterns of sickness absence 10 years after participation in 3 treatment groups (physiotherapy, cognitive behavioural therapy, and vocational multidisciplinary rehabilitation) in comparison to a control group receiving treatment-as-usual. Cost-effectiveness was also assessed. ⋯ The corresponding reduction of sickness absence after physiotherapy and cognitive behavioural therapy was not significantly different from the control group. The effect of rehabilitation seems to be more pronounced for disability pension than for sick leave. The economic analyses showed substantial cost savings for individuals in the multidisciplinary group compared to the control group.