Pain
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Injection of nerve growth factor (NGF) into the masseter muscle is not painful but does induce a localized, quick onset ( approximately 1h) and long-lasting mechanical sensitization in healthy human subjects. We tested the hypothesis that human NGF mechanically sensitizes masseter muscle nociceptors by increasing the sensitivity of peripheral N-methyl-d-aspartate (NMDA) receptors. Co-expression of the NR2B subunit of the NMDA receptor with P75 and TrkA NGF receptors by trigeminal ganglion neurons that innervate the masseter muscle was investigated immunohistochemically. ⋯ There was no effect of NGF on glutamate-evoked nociceptor discharge or glutamate-induced mechanical sensitization. Additional experiments indicated that NGF-induced mechanical sensitization could be partially attenuated with TrkA receptor antibodies, but not P75 receptor antibodies. These findings indicate that human NGF-induced sensitization of masseter nociceptors results, in part, from the activation of TrkA receptors, but does not appear to be mediated through enhanced peripheral NMDA receptor activity.
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Current clinical treatments for neuropathic pain include amitriptyline, a tricyclic antidepressant with mixed pharmacology that is also clinically reported to impair cognitive performance; and gabapentin, a compound that selectively interacts with alpha2delta-1 calcium channel subunits. Since few assessments of cognitive performance have been made in non-human primates with these marketed treatments, the purpose of this study was to determine their relative abilities to alter working memory as measured in mature macaques in their performance of a delayed matching-to-sample task. Four delay intervals of increasing duration provided increasing impairment in task accuracies during vehicle sessions. ⋯ In a series that used a task-relevant distractor to determine gabapentin's effect on attention, drug treatment reversed distractor-impaired accuracy during long delay trials (25.4% above vehicle). The selective improvement in long delay accuracy in both paradigms suggests improvement in encoding or retention components of working memory. It is currently unclear whether the ability of acute administration of gabapentin to modestly improve working memory occurs by a mechanism that could be related to its anti-allodynic mechanism of action.
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Review Meta Analysis
Randomized controlled trials of psychological therapies for management of chronic pain in children and adolescents: an updated meta-analytic review.
The purpose of this meta-analytic review was to quantify the effects of psychological therapies for the management of chronic pain in youth. Specifically, in this review we updated previous systematic reviews of randomized controlled trials by including new trials, and by adding disability and emotional functioning to pain as treatment outcomes. Electronic searches of the Cochrane Register of Randomised Controlled Trials, MEDLINE, PsycLIT, EMBASE, and the Social Sciences Citation Index were conducted from inception through August 2008. ⋯ Studies directly comparing the effects of self-administered versus therapist-administered interventions found similar effects on pain reduction. Psychological therapies result in improvement in pain relief across several different pain conditions in children. Future trials are needed that incorporate non-pain outcome domains, that focus significant therapeutic content on reductions in disability, and that include extended follow-up to better understand maintenance of treatment effects.
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Multicenter Study
Distinctiveness of psychological obstacles to recovery in low back pain patients in primary care.
Many psychological factors have been suggested to be important obstacles to recovery from low back pain, yet most studies focus on a limited number of factors. We compared a more comprehensive range of 20 factors in predicting outcome in primary care. Consecutive patients consulting 8 general practices were eligible to take part in a prospective cohort study; 1591 provided data at baseline and 810 at 6 months. ⋯ Thus, a small number of psychological factors are strongly predictive of outcome in primary care low back pain patients. There is clear redundancy in the measurement of psychological factors. These findings should help to focus targeted interventions for back pain in the future.
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Clinical Trial
NGF induces non-inflammatory localized and lasting mechanical and thermal hypersensitivity in human skin.
Nerve growth factor (NGF) modulates sensitivity and sprouting of nociceptors. We explored the spatial and temporal sensitization induced by NGF injection (1 microg) in human skin. Hyperalgesia was investigated in 16 volunteers (36+/-9 years) at day 1, 3, 7, 21, and 49. ⋯ Spatially restricted hyperalgesia indicates a peripheral rather than central mechanism. The temporal profile of lasting nociceptor sensitization suggests an altered peripheral axonal expression of sensory proteins specifically leading to mechanical and thermal sensitization. Intradermal NGF administration provokes a pattern of sensitization that can be used as experimental model for neuropathic pain.