Pain
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Growth factors such as nerve growth factor and glial cell line-derived neurotrophic factor are known to induce pain sensitization. However, a plethora of other growth factors is released during inflammation and tissue regeneration, and many of them are essential for wound healing. Which wound-healing factors also alter the sensitivity of nociceptive neurons is not well known. We studied the wound-healing factor, basic fibroblast growth factor (bFGF), for its role in pain sensitization. Reverse transcription polymerase chain reaction showed that the receptor of bFGF, FGFR1, is expressed in lumbar rat dorsal root ganglia (DRG). We demonstrated presence of FGFR1 protein in DRG neurons by a recently introduced quantitative automated immunofluorescent microscopic technique. FGFR1 was expressed in all lumbar DRG neurons as quantified by mixture modeling. Corroborating the mRNA and protein expression data, bFGF induced Erk1/2 phosphorylation in nociceptive neurons, which could be blocked by inhibition of FGF receptors. Furthermore, bFGF activated Erk1/2 in a dose- and time-dependent manner. Using single-cell electrophysiological recordings, we found that bFGF treatment of DRG neurons increased the current-density of NaV1.8 channels. Erk1/2 inhibitors abrogated this increase. Importantly, intradermal injection of bFGF in rats induced Erk1/2-dependent mechanical hyperalgesia. ⋯ Analyzing intracellular signaling dynamics in nociceptive neurons has proven to be a powerful approach to identify novel modulators of pain. In addition to describing a new sensitizing factor, our findings indicate the potential to investigate wound-healing factors for their role in nociception.
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This article reports the development of natural history and active treatment benchmarks for psychological treatments of chronic pain. The benchmarks were derived from randomized controlled trials (RCTs) reported in a published meta-analysis. In two preliminary studies we surveyed small samples of active clinicians working in U. ⋯ The average ES across outcome domains for the treatment arms was approximately 0.35. These benchmarks may be used to assess the effectiveness of routine clinical treatments for chronic pain. The application of these data and the limitations of the study are discussed.
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Menthol, the cooling natural product of peppermint, is widely used in medicinal preparations for the relief of acute and inflammatory pain in sports injuries, arthritis, and other painful conditions. Menthol induces the sensation of cooling by activating TRPM8, an ion channel in cold-sensitive peripheral sensory neurons. Recent studies identified additional targets of menthol, including the irritant receptor, TRPA1, voltage-gated ion channels and neurotransmitter receptors. ⋯ L-menthol- and WS-12-induced analgesia was blocked by naloxone, suggesting activation of endogenous opioid-dependent analgesic pathways. Our data show that TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain. In contrast to menthol, selective TRPM8 agonists may produce analgesia more effectively, with diminished side effects.
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Randomized Controlled Trial Comparative Study
Modulation of the human nociceptive flexion reflex by pleasant and unpleasant odors.
The nociceptive withdrawal reflex (NWR), a defensive response that allows withdrawal from a noxious stimulus, is a reliable index of spinal nociception in humans. It has been shown that various kinds of stimuli (emotional, visual, auditory) can modulate the transmission and perception of pain. The aim of the present study was to evaluate, by means of the NWR, the modulatory effect on the spinal circuitry of olfactory stimuli with different emotional valence. ⋯ A significant effect of olfactory stimuli on subjective pain ratings were found at both ISIs for pleasant vs unpleasant odors (P<.000), and for both pleasant and unpleasant odors vs neutral and basal conditions (P<.000). No statistical differences in subjective pain ratings at different ISIs were found. Consistent with the notion that NWR magnitude and pain perception can be modulated by stimuli with different emotional valence, these results show that olfactory stimuli, too, can modulate spinal nociception in humans.
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Vision is important for avoiding encounters with objects in the environment that may imperil physical integrity. We tested whether, in the absence of vision, a lower pain threshold would arise from an adaptive shift to other sensory channels. We therefore measured heat and cold pain thresholds and responses to suprathreshold heat stimuli in 2 groups of congenitally blind and matched normal-sighted participants. ⋯ Thresholds for nonpainful thermal stimulation did not differ between groups. The results of the pain questionnaires further indicated that blind subjects are more attentive to signals of external threats. These findings indicate that the absence of vision from birth induces a hypersensitivity to painful stimuli, lending new support to a model of sensory integration of vision and pain processing.