Pain
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Randomized Controlled Trial
Reduction of allodynia in patients with complex regional pain syndrome: A double-blind placebo-controlled trial of topical ketamine.
A double-blind placebo-controlled crossover trial was used to determine the effects of topical ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, on the sensory disturbances in 20 patients with complex regional pain syndrome (CRPS). On two occasions separated by at least one week, sensory tests to light touch, pressure, punctate stimulation, light brushing and thermal stimuli were performed in the symptomatic and contralateral limb and on each side of the forehead before and 30min after 10% ketamine cream was applied to the symptomatic or healthy limb. Venous blood for the plasma estimations of ketamine and norketamine was obtained 1h after application of the creams. ⋯ Allodynia and hyperalgesia were detected in the ipsilateral forehead to a range of stimuli (brushing, pressure, punctate stimulation, cold, heat, and warmth). In several patients, ketamine treatment of the symptomatic limb inhibited allodynia to brushing the ipsilateral forehead, suggesting that the mechanism that mediates allodynia in the symptomatic limb contributed to allodynia at more remote sites. The present study shows promise for the use of topical ketamine as opposed to parenteral and oral forms which often result in undesirable side effects.
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Deep-brain stimulation (DBS) of the posterior hypothalamus has been shown to be clinically effective for drug-resistant chronic cluster headache, but the underlying mechanism is still not understood. The hypothalamus as an important centre of homeostasis is connected among others to the trigeminal system via the trigeminohypothalamic tract. We aimed to elucidate whether hypothalamic stimulation affects thermal sensation and pain perception only in the clinically affected region (the first trigeminal branch) or in other regions as well. ⋯ Short-term interruption of stimulation did not induce any changes in DBS patients. Clinically relevant differences were found neither between non-stimulated cluster headache patients and healthy controls nor between the affected and the non-affected sides in the chronic cluster headache patients without DBS. These results support the notion that neurostimulation of the posterior hypothalamus is specific for cluster headache and only affects certain aspects of pain sensation.
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Oxaliplatin is a platinum-based chemotherapy drug characterized by the development of a painful peripheral neuropathy which is reproduced in rodent animal models with features observed in humans. Our focus was to explore the alterations of intracellular second messengers at supraspinal level in oxaliplatin-induced mechanical hyperalgesia. In our experiments, chronic administration of oxaliplatin to rats induced mechanical hyperalgesia which lasted for many days. ⋯ Distinct PKC-activated MAPK pathways, including p38MAPK, ERK1/2 and JNK, were investigated in chronic oxaliplatin rat. A dramatic phosphorylation increase, Calphostin C sensitive, could be observed in thalamus and PAG for p38MAPK. These data show that, in oxaliplatin-induced neuropathy, enhanced mechanical nociception is strictly correlated with increased phosphorylation of specific intracellular mediators in PAG and thalamus brain regions pointing to a role of these supraspinal centers in oxaliplatin-induced neuropathic pain mechanism.
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Patients with neuropathic pain syndromes are heterogeneous. They present with a variety of sensory symptoms and pain qualities. The knowledge of these data and etiology-specific differences is important to optimize clinical trial design and to develop more effective drugs. ⋯ All subgroups occur in relevant numbers in both entities but the frequencies differ between PHN and DPN. Since sensory symptoms likely translate into pain-generating mechanisms enrichment for potential treatment responders might be possible in clinical trials by assessing the sensory profiles. Patient-Reported Outcomes can be used to obtain a precise sensory characterization of each patient.