Articles: hyperalgesia.
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Randomized Controlled Trial Comparative Study
Topically administered ketamine reduces capsaicin-evoked mechanical hyperalgesia.
The n-methyl-d-aspartate receptor antagonists such as ketamine relieve chronic pain but their oral and parenteral use is limited by the adverse effects. Experimental studies indicate that the peripheral n-methyl-d-aspartate receptors are involved in nociception. Recent clinical findings suggest that ketamine gel alleviates neuropathic pain, but no placebo-controlled randomized studies are available on the neurosensory effects of ketamine gel in experimental neurogenic pain. ⋯ A significant reduction of mechanical hyperalgesia was produced by topically and pre-emptively applied ketamine in healthy patients. We propose that the mechanism of action would be the reduction of central sensitization caused by the absorption of ketamine in circulation.
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Randomized Controlled Trial
A PET activation study of brush-evoked allodynia in patients with nerve injury pain.
Acute experimental brush-evoked allodynia induces a cortical activation pattern that differs from that typically seen during experimental nociceptive pain. In this study, we used positron emission tomography to measure changes in regional cerebral blood flow (rCBF) in patients with clinical allodynia. Nine patients with peripheral nerve injury were scanned during rest, brush-evoked allodynia, and brushing of normal contralateral skin. ⋯ A direct post hoc comparison of brush -and allodynia-induced rCBF changes showed that allodynia was associated with significantly stronger activations in orbitofrontal cortex and ipsilateral insula whereas non-painful brushing more strongly activated SI and BA 5/7. These findings indicate that activity in the cortical network involved in the sensory-discriminative processing of nociceptive pain is downregulated in neuropathic pain. Instead, there is an upregulation of activity in the orbitofrontal and insular cortices, which is probably due to the stronger emotional load of neuropathic pain and higher computational demands of processing a mixed sensation of brush and pain.
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Proc. Natl. Acad. Sci. U.S.A. · Dec 2005
Randomized Controlled Trial Comparative StudyPharmacological modulation of pain-related brain activity during normal and central sensitization states in humans.
Abnormal processing of somatosensory inputs in the central nervous system (central sensitization) is the mechanism accounting for the enhanced pain sensitivity in the skin surrounding tissue injury (secondary hyperalgesia). Secondary hyperalgesia shares clinical characteristics with neurogenic hyperalgesia in patients with neuropathic pain. Abnormal brain responses to somatosensory stimuli have been found in patients with hyperalgesia as well as in normal subjects during experimental central sensitization. ⋯ We found that (i) gabapentin reduced the activations in the bilateral operculoinsular cortex, independently of the presence of central sensitization; (ii) gabapentin reduced the activation in the brainstem, only during central sensitization; (iii) gabapentin suppressed stimulus-induced deactivations, only during central sensitization; this effect was more robust than the effect on brain activation. The observed drug-induced effects were not due to changes in the baseline fMRI signal. These findings indicate that gabapentin has a measurable antinociceptive effect and a stronger antihyperalgesic effect most evident in the brain areas undergoing deactivation, thus supporting the concept that gabapentin is more effective in modulating nociceptive transmission when central sensitization is present.
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Randomized Controlled Trial Comparative Study
Different profiles of buprenorphine-induced analgesia and antihyperalgesia in a human pain model.
Different mechanisms were proposed for opioid-induced analgesia and antihyperalgesia, which might result in different pharmacodynamics. To address this issue, the time course of analgesic and antihyperalgesic effects of intravenous (i.v.) and sublingual (s.l.) buprenorphine was assessed in an experimental human pain model. Fifteen volunteers were enrolled in this randomized, double-blind, and placebo controlled cross-over study. ⋯ The half-life of buprenorphine-induced analgesic and antihyperalgesic effects were 171 and 288 min, respectively. In contrast to pure mu-receptor agonists, buprenorphine exerts a lasting antihyperalgesic effect in our model. It will be of major clinical interest whether this difference will translate into improved treatment of pain states dominated by central sensitization.
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Randomized Controlled Trial
Activation of naloxone-sensitive and -insensitive inhibitory systems in a human pain model.
We investigated naloxone effects in a model of electrically induced pain and hyperalgesia. In a double-blind, placebo-controlled, cross-over study, 15 volunteers underwent four 150-minute sessions of high-current-density electrical stimulation of their forearms. After 60 minutes, naloxone or placebo was given intravenously (increasing plasma concentrations of 0.1, 1, and 10 ng/mL; 30 minutes each) in 3 of the 4 sessions. Pain ratings and areas of mechanical hyperalgesia were assessed at regular intervals during all sessions. The low doses of naloxone did not cause any significant change of pain rating of areas of hyperalgesia. In terms of intrasession effects, pain ratings and areas of hyperalgesia significantly decreased during the sessions to 62% (pain rating), 70% (area of punctuate hyperalgesia), and 82% (area of allodynia) of the initial values. Naloxone (10 ng/ml) reversed these decreases. In terms of between-session effects, the time course of pain ratings remained constant from session to session. In contrast, the areas of punctate hyperalgesia successively decreased to 60% of initial value at the fourth repetition. The session effect was not reversed by naloxone. High-current-density electrical stimulation provokes central sensitization, but in addition inhibitory systems are activated that are only partly naloxone-sensitive. ⋯ Endogenous inhibitory systems are of major importance for clinical pain conditions, but are not reflected in traditional human pain models. Here we show activation of a naloxone-sensitive short-term and a naloxone-insensitive long-term inhibitory system in a new model of electrically induced pain and hyperalgesia.