Articles: neuralgia.
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Refractory to most types of treatment, neuropathic pain (NP) is a major problem for people living with spinal cord injury (SCI). The underlying mechanisms among problems related to treatment are poorly understood. The aim of the present study was to investigate the association between cortical reorganization and NP after SCI. Twenty-four individuals with sensorimotor complete and incomplete paraplegia and tetraplegia (12 with NP, 13 pain free) and 31 healthy individuals were examined. Functional magnetic resonance imaging was used to assess activation in primary somatosensory and motor cortices in response to motor (ie, active and passive wrist extension) and sensory (ie, heat and brushing) tasks applied on the dorsum of the hand. In individuals with SCI, there were no group-level differences in task-related activation (ie, movement or sensory) compared with the healthy controls. However, based on the Euclidean distance measure, individuals with SCI demonstrated a lateral shift of peak activity in primary sensory and motor cortices (P < .05). Among those with NP, chronic pain intensity inversely correlated with the magnitude of the shift in the primary motor cortex during active wrist extension. The findings reveal that NP in motor and sensory tasks at or above the level of the lesion is not associated with increased plasticity. In line with previous studies, changes in somatotopy and activation after SCI are rather limited and the influence of NP on plasticity remains controversial. ⋯ Using functional magnetic resonance imaging, we have provided novel evidence that reorganization (i.e., topographical shifts in peak activity) in the primary motor cortex after spinal cord injury is limited to individuals without neuropathic pain.
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To determine the direct and indirect effects of function on clinical variables such as age, pain intensity, years of the disease, severity of symptoms, and depression in women with electrodiagnostic and clinical diagnosis of carpal tunnel syndrome (CTS). ⋯ Our study demonstrated that function mediates the relationship between depression and symptoms severity with pain intensity in women with CTS. Future longitudinal studies will help to determine the clinical implications of these findings.
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Neuropsychopharmacology · Dec 2015
A Cannabinoid CB1 Receptor-Positive Allosteric Modulator Reduces Neuropathic Pain in the Mouse with No Psychoactive Effects.
The CB1 receptor represents a promising target for the treatment of several disorders including pain-related disease states. However, therapeutic applications of Δ(9)-tetrahydrocannabinol and other CB1 orthosteric receptor agonists remain limited because of psychoactive side effects. Positive allosteric modulators (PAMs) offer an alternative approach to enhance CB1 receptor function for therapeutic gain with the promise of reduced side effects. ⋯ In the whole animal, ZCZ011 is brain penetrant, increased the potency of these orthosteric agonists in mouse behavioral assays indicative of cannabimimetic activity, including antinociception, hypothermia, catalepsy, locomotor activity, and in the drug discrimination paradigm. Administration of ZCZ011 alone was devoid of activity in these assays and did not produce a conditioned place preference or aversion, but elicited CB1 receptor-mediated antinociceptive effects in the chronic constriction nerve injury model of neuropathic pain and carrageenan model of inflammatory pain. These data suggest that ZCZ011 acts as a CB1 PAM and provide the first proof of principle that CB1 PAMs offer a promising strategy to treat neuropathic and inflammatory pain with minimal or no cannabimimetic side effects.
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Painful diabetic neuropathy is a common complication of diabetes produced by mechanisms that as yet are incompletely defined. The aim of this study was to investigate the roles of nuclear factor-κB (NF-κB) in the regulation of purinergic receptor P2X ligand-gated ion channel 3 (P2X3R) plasticity in dorsal root ganglion (DRG) neurons of rats with painful diabetes. Here, we showed that hindpaw pain hypersensitivity in streptozocin-induced diabetic rats was attenuated by treatment with purinergic receptor antagonist suramin or A-317491. ⋯ The inhibition of p65 signaling using the NF-κB inhibitor pyrrolidine dithiocarbamate or recombinant lentiviral vectors designated as lentiviral vector-p65 small interfering RNA remarkably suppressed P2X3R activities and attenuated diabetic pain hypersensitivity. Insulin treatment significantly attenuated pain hypersensitivity and suppressed the expression of p65 and P2X3Rs. Our findings suggest that the p2x3r gene promoter DNA demethylation and enhanced interaction with p65 contributes to P2X3R sensitization and diabetic pain hypersensitivity.
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Postherpetic neuralgia (PHN) is a particularly challenging neuropathic pain condition, especially when it involves the trigeminal nerve. Peripheral nerve stimulation (PNS) can provide 50-70% improvement in pain to many who fail medical management. However, this pain relief can be incomplete, and residual pain may persist for many years. Here we report a case that was successfully managed by a novel technique of combining supraorbital nerve stimulation with botulinum toxin type A (BTA) for intractable ophthalmic PHN. ⋯ In a patient with trigeminal PHN, local injection of BTA effectively reduced pain remaining after treatment with PNS.