Pain
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Cancer patients treated with antimitotic drugs in the taxane and vinca alkaloid classes sometimes develop a chronic painful peripheral neuropathy whose cause is not understood. In animal models of painful peripheral neuropathy due to nerve trauma or diabetes there is obvious axonal degeneration accompanied by an abnormal incidence of spontaneous discharge in A-fiber and C-fiber nociceptors. But animals with paclitaxel- and vincristine-evoked neuropathic pain do not have axonal degeneration at the level of the peripheral nerve. ⋯ Compared to vehicle-injected controls, we find a significant increase in spontaneously discharging A-fibers and C-fibers. Moreover, we show that prophylactic treatment with acetyl-l-carnitine (ALC), which blocks the development of the paclitaxel-evoked pain, causes a significant decrease (ca. 50%) in the incidence of A-fibers and C-fibers with spontaneous discharge. These results suggest that abnormal spontaneous afferent discharge is likely to be a factor in the pathogenesis of chemotherapy-evoked painful peripheral neuropathy, and that the therapeutic effects of ALC may be due to the suppression of this discharge.
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Randomized Controlled Trial
Pharmacological dissection of the paradoxical pain induced by a thermal grill.
We investigated the role of the glutamatergic and endogenous opioidergic systems in the paradoxical pain evoked by the simultaneous application of innocuous warm and cold stimuli to the skin with a "thermal grill". Two parallel randomized, double-blind, cross-over studies, including two groups of 12 healthy volunteers, were carried out to compare the effects of i.v. ketamine or naloxone to those of placebo, on the sensations produced by a thermode (i.e. thermal grill) composed of six bars applied on the palmar surface of the right hand. The temperature of alternate (even- and odd-numbered) bars could be controlled independently by Peltier elements to produce various patterns of the grill. ⋯ By contrast, naloxone had no effect on paradoxical pain, normal pain or non-painful thermal sensations. This study demonstrates for the first time that the "thermal grill illusion of pain" can be modulated pharmacologically. This paradoxical pain, which involves the glutamatergic systems, acting through the NMDA receptors, but not the tonic endogenous opioids systems, might share some mechanisms with pathological pain.
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Psychosocial factors are crucial for understanding and treating chronic pain in adults, but also in children. For children, very few questionnaires for a multidimensional pain assessment exist. In adults, the Multidimensional Pain Inventory (MPI; [Kerns RD, Turk DC, Rudy TE. ⋯ Validity analyses yielded a pattern of correlations with measures of depression, trait anxiety, pain activity, child behaviors, pain-related cognitions, and parenting behavior that is consistent with psychometric data of the adult MPI and previous findings on psychosocial aspects of chronic pediatric pain. Significant differences between children depending on patient status (participants in experimental or treatment studies, outpatients, inpatients) suggest external validity of the PEQ. Despite the preliminary nature of the psychometric evaluation, the child and parent PEQ seem promising for a comprehensive assessment of pediatric pain.