Pain
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Cold allodynia, pain in response to cooling, occurs during or within hours of oxaliplatin infusion and is thought to arise from a direct effect of oxaliplatin on peripheral sensory neurons. To characterize the pathophysiological mechanisms underlying acute oxaliplatin-induced cold allodynia, we established a new intraplantar oxaliplatin mouse model that rapidly developed long-lasting cold allodynia mediated entirely through tetrodotoxin-sensitive Nav pathways. ⋯ Intraplantar injection of the Nav1.6 activator Cn2 elicited spontaneous pain, mechanical allodynia, and enhanced 4-aminopyridine-induced cold allodynia. These findings provide behavioural evidence for a crucial role of Nav1.6 in multiple peripheral pain pathways including cold allodynia.
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Sciatica after disc herniation may be associated with compression of spinal nerves, but also inflammatory substances released from the nucleus pulposus (NP) leaking into the spinal canal. Here, in an animal model mimicking clinical intervertebral disc herniation, we investigate the effect of NP on neuronal activity. In anaesthetized Lewis rats, extracellular single-unit recordings of spinal dorsal horn neurons were performed, and the C-fibre responses were examined. ⋯ In accordance with earlier studies, we showed a significant increase in the C-fibre response and an upregulation of the gene expression of interleukin 1β and tumour necrosis factor 180 minutes after application of NP onto the nerve roots. Moreover, based on a polymerase chain reaction array of 84 common inflammatory cytokines at the same time point, we demonstrated a highly significant upregulation of colony-stimulating factor 1 also termed macrophage colony-stimulating factor and Fas ligand. The pronounced upregulation of Csf1 and Fas ligand 180 minutes after application of NP onto the nerve roots suggests that macrophage activation and apoptosis may be involved in pain hypersensitivity and other sensory abnormalities after disc herniation.
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Cannabinoid agonists such as Δ(9)-tetrahydrocannabinol (THC) are more potent and/or efficacious antinociceptive agents in female than male rats using acute pain models. We tested the hypothesis that THC is more effective in females than males using a model of longer-lasting, inflammatory pain. THC's anti-allodynic, anti-hyperalgesic, and anti-edema effects were examined 1, 3, and 7 days after injection of complete Freund's adjuvant (CFA) into the hind paw. ⋯ THC's anti-edema effect in males. This study suggests that cannabinoids may be better at reducing edema in males while being more effective against inflammatory pain in females. Furthermore, sex differences in THC's peripheral effects against inflammatory pain may be a result of activation of both types of cannabinoid receptors in females, in contrast to predominantly CB1 receptors in males.
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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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Randomized Controlled Trial Multicenter Study
Endogenous opioid function mediates the association between laboratory-evoked pain sensitivity and morphine analgesic responses.
Predictors of responsiveness to opioid analgesic medications are not well understood. This study tested whether individual differences in endogenous opioid (EO) function are associated with analgesic responsiveness to morphine. In randomized, counterbalanced order over 3 sessions, 45 chronic low back pain participants and 31 healthy controls received an opioid antagonist (8 mg naloxone), morphine (0.08 mg/kg), or placebo. ⋯ These latter associations were significantly mediated by EO function for 4 of these 5 pain outcomes (all P values<0.05). In the laboratory-evoked pain context, opioid analgesic medications may supplement inadequate EO analgesia, with little incremental benefit in those with preexisting high EO function. Implications for personalized medicine are discussed.