Articles: hyperalgesia.
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Animal models in pain research have suggested that inclusion of both evoked and nonevoked behavioral measures is needed to better reflect the human pain experience. Individuals with chronic pain are known to experience spontaneous pain, in addition to pain after exposure to an external stimulus. Recently, the dynamic weight bearing (DWB) apparatus was developed to assess for nonevoked hyperalgesia by capturing weight bearing and surface distribution in the paws of mice after acute inflammation. ⋯ Mice with inflammation showed alterations in weight bearing as well as increased thermal hyperalgesia in comparison with control groups. These findings support the use of the DWB test as a tool for measuring nonevoked inflammatory hyperalgesia in a mouse model.
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Review Meta Analysis
From "mechanical" to "neuropathic" back pain concept in FBSS patients. A systematic review based on factors leading to the chronification of pain (part C).
Beyond initial lesions, any form of spinal (re)operation can cause direct potential aggression to the nervous system by contact with neural tissue or by imprinting a morphological change on the neural tissue. The potential consequences of nerve root injury affect both peripheral and axial dermatomal distribution. The hypothesis of a possible neuropathic aspect associated with the back pain component of failed back surgery syndrome (FBSS) therefore appears to be reasonable. Its pathophysiology remains unclear due to the permanent interplay between nociceptive and neuropathic pain components, resulting in the coexistence of physiological and pathological pain at the same anatomical site. This paper is designed to extensively review the fundamental mechanisms leading to chronification of pain and to suggest considering the emerging concept of "neuropathic back pain". ⋯ A clear understanding of the factors leading to the chronification of back pain should help us to move to the choice of mechanism related pain treatments to improve outcomes in FBSS chronic condition.
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Randomized Controlled Trial
GABAergic modulation in central sensitization in humans: a randomized placebo-controlled pharmacokinetic-pharmacodynamic study comparing clobazam with clonazepam in healthy volunteers.
Positive allosteric modulators of GABAA receptors (GAMs) acting at specific subtypes of GABAA receptors effectively restore compromised spinal pain control in rodents. Studies addressing a similar antihyperalgesic effect in humans are sparse and are hampered by sedative effects of nonselective GAMs available for use in humans. We present results from a randomized controlled double-blind crossover study in 25 healthy volunteers, which addressed potential antihyperalgesic actions of clobazam (CBZ) and clonazepam (CLN) at mildly sedating equianticonvulsive doses. ⋯ Active compounds induced stronger sedation than placebo, but these differences disappeared 8 hours after drug application. We demonstrate here that GAMs effectively reduce central sensitization in healthy volunteers. These results provide proof-of-principle evidence supporting efficacy of GAMs as antihyperalgesic agents in humans and should stimulate further research on compounds with improved subtype specificity.
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Biological psychiatry · Mar 2015
Chronic cannabinoid receptor 2 activation reverses paclitaxel neuropathy without tolerance or cannabinoid receptor 1-dependent withdrawal.
Mixed cannabinoid receptor 1 and 2 (CB1 and CB2) agonists such as Δ(9)-tetrahydrocannabinol (Δ(9)-THC) can produce tolerance, physical withdrawal, and unwanted CB1-mediated central nervous system side effects. Whether repeated systemic administration of a CB2-preferring agonist engages CB1 receptors or produces CB1-mediated side effects is unknown. ⋯ Our results highlight the potential of prolonged use of CB2 agonists for managing chemotherapy-induced allodynia with a favorable therapeutic ratio marked by sustained efficacy and absence of tolerance, physical withdrawal, or CB1-mediated side effects.
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There are only 2 small sample studies investigating allodynia in the pediatric population. The aim of this study was to evaluate the frequency of allodynia during cephalalgic attacks in a juvenile population with primary headaches and its association with other symptoms of migraine. ⋯ According to our data, allodynia is common during pediatric migraine attacks. The association between allodynia and physical activity, nausea and phonophobia are supported by studies on adult population and suggests specific physiopathological mechanisms.