Articles: hyperalgesia.
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Arzneimittel Forsch · Jan 2004
Randomized Controlled Trial Clinical TrialAnalgesic effects of low-dose intravenous orphenadrine in the state of capsaicin hyperalgesia. A randomised, placebo-controlled, double-blind cross-over study using laser somatosensory evoked potentials obtained from capsaicin-irritated skin in healthy volunteers.
The present investigation aimed to elucidate the analgesic efficacy of 30 mg of intravenous orphenadrine citrate (CAS 4682-36-4) in a human pain model. Eighteen healthy female and male subjects were enrolled and received single infusions of 30 mg orphenadrine citrate and matching placebo in two periods which were separated by a 1 week washout period. The study was designed as a randomised, double-blind, placebo-controlled, two-period, cross-over trial. ⋯ The effect on the central component was highly significant and more pronounced than the peripheral effect of the drug. The analgesic effect developed fast, was already present during infusion, was ongoing, and exceeded the observational period of 4 h after start of infusion. In summary, orphenadrine citrate was able to exert an analgesic/anti-hyperalgesic effect in a low-dose paradigm (30 mg dose) which was predominantly due to central/spinal mechanisms in this capsaicin model with laser somatosensory evoked potentials.
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J. Invest. Dermatol. · Jan 2004
Ultraviolet radiation-induced inflammation as a model for cutaneous hyperalgesia.
The effects of UVA-I and solar simulated radiation on skin sensitivity to thermal and mechanical stimuli were compared in normal volunteers. Individual minimal erythema doses (MED) for each source were determined and previously unexposed buttock skin was exposed to 1, 2 and 3 MED of each spectrum. Erythema, and mechanical and thermal pain thresholds were quantified from 3 to 72 hours post-irradiation. ⋯ These data demonstrate the usefulness of UVR-induced inflammation as a model of cutaneous hypersensitivity. This model has clinical relevance for the study of hyperalgesia in general and the abnormal sensitivity of sunburnt skin in particular. It is likely to be useful in the assessment of peripherally acting analgesic drugs.
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Anesthesia and analgesia · Jan 2004
Randomized Controlled Trial Clinical TrialThe sunburn pain model: the stability of primary and secondary hyperalgesia over 10 hours in a crossover setting.
It was our aim to study the within-day stability and between-day repeatability of ultraviolet B (UVB) light-induced primary and secondary hyperalgesia over 10 h. Twenty hours after UVB irradiation of a skin spot (r = 2.5 cm) on the upper leg of 8 healthy volunteers the areas of secondary hyperalgesia to pinprick and pain tolerance thresholds to heat (HPTT) and electrical stimuli (5 and 250 Hz, electrical pain tolerance thresholds [EPTT]) were assessed. Measurements were repeated for 10 h at 2-h intervals and in 2 different sessions. Large areas of secondary hyperalgesia to pin prick were observed (5995 mm(2); SD, 1645). Primary hyperalgesia was evidenced by significant decreases of HPTT (mean difference, 6.5 degrees C; 95% confidence interval, 6.1-6.8; P < 0.001) and EPTT at 250 Hz (mean difference, 0.45 mA; 95% confidence interval, 0.13-0.78; P < 0.05) compared to normal skin. There was no trend within one session of either primary (P = 0.14 for HPTT) or secondary hyperalgesia (P = 0.95) and no difference between the two sessions (primary hyperalgesia, P = 0.28; secondary hyperalgesia, P = 0.07). The sunburn pain model provides a long time course of stable hyperalgesia with a high within-day stability and between-day repeatability for primary and secondary hyperalgesia. ⋯ The sunburn pain model provides a long time course of stable hyperalgesia with a high within-day stability and between-day repeatability for primary and secondary hyperalgesia.
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Transmission of noxious-stimulus-evoked inputs in the spinal and trigeminal systems is mediated primarily through excitatory glutamatergic synapses using alpha amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA), kainate and N-methyl-D-aspartate (NMDA) subtypes of glutamate receptors. Glutamatergic synapses exhibit multiple forms of short-lasting and long-lasting synaptic plasticity. Persistent enhancement of nociceptive transmission, known as "central sensitization," is a form of lasting plasticity that is similar mechanistically to long-term potentiation of glutamatergic transmission in other regions of the central nervous system. ⋯ Central sensitization is thus an expression of increased synaptic gain at glutamatergic synapses in central nociceptive-transmission neurons and thereby contributes importantly to pain hypersensitivity. In addition, recent evidence has revealed a new player in the mechanisms underlying pain hypersensitivity following nerve injury--microglia. Understanding of the roles of microglia may lead to new strategies for the diagnosis and management of neuropathic pain.