Pain
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TRPA1 is an ion channel of the TRP family that is expressed in some sensory neurons. TRPA1 activity provokes sensory symptoms of peripheral neuropathy, such as pain and paraesthesia. We have used a grease gap method to record axonal membrane potential and evoked compound action potentials (ECAPs) in vitro from human sural nerves and studied the effects of mustard oil (MO), a selective activator of TRPA1. ⋯ Capsaicin caused a profound reduction in C fibre conduction in both species but had no effect on the amplitude of the A component. Lidocaine (30 mM) depolarized rat saphenous nerves acutely, and when rat nerves were pretreated with 30 mM lidocaine to mimic the exposure of human nerves to local anaesthetic during surgery, the effects of MO were abolished whilst the effects of capsaicin were unchanged. This study demonstrates that the local anaesthetic lidocaine desensitizes TRPA1 ion channels and indicates that it may have additional mechanisms for treating neuropathic pain that endure beyond simple sodium channel blockade.
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Brain responses to the activation of C-fibres are obtained only if the co-activation of Aδ-fibres is avoided. Methods to activate C-fibres selectively have been proposed, but are unreliable or difficult to implement. Here, we propose an approach combining a new laser stimulator to generate constant-temperature heat pulses with an adaptive paradigm to maintain stimulus temperature above the threshold of C-fibres but below that of Aδ-fibres, and examine whether this approach can be used to record reliable C-fibre laser-evoked brain potentials. ⋯ Reliable individual-level electroencephalogram (EEG) responses were identified, both in the time domain (hand: N2: 704 ± 179 ms, P2: 984 ± 149 ms; foot: N2: 1314 ± 171 ms, P2: 1716 ± 171 ms) and the time-frequency (TF) domain. Using a control dataset in which no stimuli were delivered, a Receiver Operating Characteristics analysis showed that the magnitude of the phase-locked EEG response corresponding to the N2-P2, objectively quantified in the TF domain, discriminated between absence vs presence of C-fibre responses with a high sensitivity (hand: 85%, foot: 80%) and specificity (hand: 90%, foot: 75%). This approach could thus be particularly useful for the diagnostic workup of small-fibre neuropathies and neuropathic pain.
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Randomized Controlled Trial
Management of acute whiplash: A randomized controlled trial of multidisciplinary stratified treatments.
Acute whiplash is a heterogeneous disorder that becomes persistent in 40% to 60% of cases. Estimates of recovery have not changed in recent decades. This randomized, single-blind, controlled trial tested whether multidisciplinary individualized treatments for patients with acute whiplash (<4 weeks postinjury) could reduce the incidence of chronicity at 6 mo by 50% compared to usual care. ⋯ Analysis revealed no significant differences in frequency of recovery (NDI ≤ 8%) between pragmatic and usual care groups at 6 months (OR 95%, CI=0.55, 0.23-1.29), P=0.163) or 12 mo (OR 95%, CI=0.65, 0.28-1.47, P=0.297). There was no improvement in current nonrecovery rates at 6 mo (63.6%, pragmatic care; 48.8%, usual care), indicating no advantage of the early multiprofessional intervention. Baseline levels of pain and disability had a significant bearing on recovery both at 6 and 12 mo in both groups, suggesting that future research focus on finding early effective pain management, particularly for the subgroup of patients with initial high levels of pain and disability, towards improving recovery rates.
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To explore definitions for multisite pain, and compare associations with risk factors for different patterns of musculoskeletal pain, we analysed cross-sectional data from the Cultural and Psychosocial Influences on Disability (CUPID) study. The study sample comprised 12,410 adults aged 20-59 years from 47 occupational groups in 18 countries. A standardised questionnaire was used to collect information about pain in the past month at each of 10 anatomical sites, and about potential risk factors. ⋯ In comparison with pain involving only 1-3 sites, it showed much stronger associations (relative to no pain) with risk factors such as female sex (PRR 1.6 vs 1.1), older age (PRR 2.6 vs 1.1), somatising tendency (PRR 4.6 vs 1.3), and exposure to multiple physically stressing occupational activities (PRR 5.0 vs 1.4). After adjustment for number of sites with pain, these risk factors showed no additional association with a distribution of pain that was widespread according to the frequently used American College of Rheumatology criteria. Our analysis supports the classification of pain at multiple anatomical sites simply by the number of sites affected, and suggests that extensive pain differs importantly in its associations with risk factors from pain that is limited to only a small number of anatomical sites.