Articles: hyperalgesia.
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Randomized Controlled Trial
The effect of a combination of gabapentin and donepezil in an experimental pain model in healthy volunteers: results of a randomized controlled trial.
This double-blind, placebo-controlled, 3-period cross-over, 4-treatment option, incomplete block study (ClinicalTrials.gov number NCT01485185), with an adaptive design for sample size re-estimation, was designed to evaluate gabapentin plus donepezil in an established experimental model of electrical hyperalgesia. Thirty healthy male subjects aged 18-55 years were randomized to receive gabapentin 900 mg or gabapentin 900 mg+donepezil 5mg for 2 of the 3 treatment periods, with 50% of subjects randomized to receive placebo (negative control) and 50% to gabapentin 1800 mg (positive control) for the remaining period. Each treatment period was 14 days. ⋯ Gabapentin+donepezil (n=30) significantly reduced the area of hyperalgesia vs gabapentin 900 mg (n=30; -11.73 cm(2); 95% CI -21.04 to -2.42; P=0.014), with supportive results for allodynia (-6.62 cm(2); 95% CI -13.29-0.04; P=0.052). The adverse event profile for gabapentin+donepezil was similar to the same dose of gabapentin. Data are supportive of further clinical investigation of a gabapentin-and-donepezil combination in patients with an inadequate response to gabapentin.
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Comparative Study
TRPA1 contributes to capsaicin-induced facial cold hyperalgesia in rats.
Orofacial cold hyperalgesia is known to cause severe persistent pain in the face following trigeminal nerve injury or inflammation, and transient receptor potential (TRP) vanilloid 1 (TRPV1) and TRP ankylin 1 (TRPA1) are thought to be involved in cold hyperalgesia. However, how these two receptors are involved in cold hyperalgesia is not fully understood. To clarify the mechanisms underlying facial cold hyperalgesia, nocifensive behaviors to cold stimulation, the expression of TRPV1 and TRPA1 in trigeminal ganglion (TG) neurons, and TG neuronal excitability to cold stimulation following facial capsaicin injection were examined in rats. ⋯ Approximately 30% of TG neurons innervating the lateral facial skin expressed both TRPV1 and TRPA1, and about 64% of TRPA1-positive neurons also expressed TRPV1. The TG neuronal excitability to noxious cold stimulation was significantly increased following facial capsaicin injection and this increase was recovered by pretreatment with TRPA1 antagonist. These findings suggest that TRPA1 sensitization via TRPV1 signaling in TG neurons is involved in cold hyperalgesia following facial skin capsaicin injection.
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Hyperalgesia in different musculoskeletal structures including bones is a major clinical problem. An experimental bone hyperalgesia model was developed in the present study. Hyperalgesia was induced by three different weights impacted on the shinbone in 16 healthy male and female subjects. ⋯ Females developed more pronounced hyperalgesia reflected in reduced IPTs and PPTs (p < 0.05). Temporal summation was significantly (p < 0.05) facilitated after induction of hyperalgesia with the strongest facilitation in males. The developed bone pain and hyperalgesia model may provide the basis for studying this fundamental mechanism of bone-related hyperalgesia and be used for profiling compounds developed for this target.
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Relationships between the paradoxical painful and non painful sensations induced by a thermal grill.
The simultaneous application of innocuous cutaneous warm and cold stimuli with a thermal grill can induce both paradoxical pain and paradoxical warmth (heat). The goal of this study was to investigate further the relationships between these paradoxical sensations. Stimuli were applied to the palms of the right hands of 21 volunteers with a thermode consisting of 6 bars, the temperature of which was controlled by Peltier elements. ⋯ The intensities of the warmth and unpleasantness evoked by the stimuli were directly related to the magnitude of the warm-cold differential. Our results suggest that there is a continuum between the painful and nonpainful paradoxical sensations evoked by the thermal grill that may share pathophysiological mechanisms. These data also confirm the existence of strong relationships between the thermoreceptive and nociceptive systems and the utility of the thermal grill for investigating these relationships.
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Neuroscience bulletin · Dec 2014
Toll-like receptor 4-mediated nuclear factor-κB activation in spinal cord contributes to chronic morphine-induced analgesic tolerance and hyperalgesia in rats.
Nuclear factor kappa B (NF-κB) in the spinal cord is involved in pro-inflammatory cytokine-mediated pain facilitation. However, the role of NF-κB activation in chronic morphine-induced analgesic tolerance and the underlying mechanisms remain unclear. In the present study, we found that the level of phosphorylated NF-κB p65 (p-p65) was increased in the dorsal horn of the lumbar 4-6 segments after intrathecal administration of morphine for 7 consecutive days, and the p-p65 was co-localized with neurons and astrocytes. ⋯ In another experiment, rats receiving PDTC or SN50 beginning on day 7 of morphine injection showed partial recovery of the anti-nociceptive effects of morphine and attenuation of the withdrawal-induced abnormal pain. Meanwhile, intrathecal pretreatment with lipopolysaccharide from Rhodobacter sphaeroides, an antagonist of toll-like receptor 4 (TLR4), blocked the activation of NF-κB, and prevented the development of morphine tolerance and withdrawal-induced abnormal pain. These data indicated that TLR4-mediated NF-κB activation in the spinal cord is involved in the development and maintenance of morphine analgesic tolerance and withdrawal-induced pain hypersensitivity.