Different patterns of hyperalgesia induced by experimental inflammation in human skin
TL;DR: It was concluded that both hyperalgesia to punctate stimuli and brush-evoked pain are due to central nervous plasticity changes rather than nociceptor sensitization.
Abstract: Different types of hyperalgesia were studied after experimental induction of inflammation in small skin areas of healthy volunteers either by topical application of capsaicin solution (1% in 70% ethanol) or by briefly freezing a skin area of similar size to -28 degrees C Sensory tests were performed 30 min after capsaicin application and 22 h after freeze lesions Heat pain thresholds were lowered after both treatments, probably due to nociceptor sensitization Hyperalgesia to four types of mechanical stimulation was studied (i) Hyperalgesia to punctate stimuli was encountered at the skin site directly affected by the noxious chemical or freeze stimulus (1 degree zone) and in the surrounding skin (2 degrees zone) in both models though the area of 2 degrees hyperalgesia to punctate stimuli after freezing was smaller than after capsaicin (ii) Hyperalgesia to gently brushing the skin was prominent after capsaicin in 1 degree and 2 degrees zone, but almost absent after freezing It was concluded that both hyperalgesia to punctate stimuli and brush-evoked pain are due to central nervous plasticity changes rather than nociceptor sensitization As revealed by differential nerve blocks, brush-evoked pain is mediated by low threshold mechanosensitive A beta-fibres, whilst hyperalgesia to punctate stimuli can be elicited when only C-fibres conduct In contrast to hyperalgesia to punctate stimuli it requires continuous background discharges in nociceptor units (iii) Pressure hyperalgesia to tonic stimulation with a blunt probe was encountered in the 1 degree zone of both types of inflammation and is probably due to recruitment of sensitized nociceptor units (iv) Impact hyperalgesia was studied by shooting small bullets against the skin at predetermined velocities It was found in the 1 degree zone after freezing and absent in the capsaicin model Differential nerve blocks revealed that it is probably mediated by sensitized C-fibres In conclusion, different types of inflammatory changes may result in characteristic different patterns of hyperalgesia
Citations
More filters
TL;DR: Here, a conceptual framework for the contribution of plasticity in primary sensory and dorsal horn neurons to the pathogenesis of pain is developed, identifying distinct forms of Plasticity, which are term activation, modulation, and modification, that by increasing gain, elicit pain hypersensitivity.
Abstract: We describe those sensations that are unpleasant, intense, or distressing as painful. Pain is not homogeneous, however, and comprises three categories: physiological, inflammatory, and neuropathic pain. Multiple mechanisms contribute, each of which is subject to or an expression of neural plasticity-the capacity of neurons to change their function, chemical profile, or structure. Here, we develop a conceptual framework for the contribution of plasticity in primary sensory and dorsal horn neurons to the pathogenesis of pain, identifying distinct forms of plasticity, which we term activation, modulation, and modification, that by increasing gain, elicit pain hypersensitivity.
3,543 citations
TL;DR: A global account of mechanisms involved in the induction of pain is provided, including neuronal pathways for the transmission of nociceptive information from peripheral nerve terminals to the dorsal horn, and therefrom to higher centres.
1,752 citations
Cites background from "Different patterns of hyperalgesia ..."
...Such changes are accompaniedÐthough not invariablyÐby spontaneous pain (Bessou and Perl, 1969; Kilo et al., 1994)....
[...]
TL;DR: A comprehensive QST protocol is compiled using well established tests for nearly all aspects of somatosensation to test for patterns of sensory loss or gain, and to assess both cutaneous and deep pain sensitivity.
1,147 citations
TL;DR: More insights are needed into pain mechanisms in OA to enable rational mechanism-based management of pain and to contribute to a substantial socioeconomic burden.
1,096 citations
TL;DR: Transcriptional changes both potentiate the system and alter neuronal phenotype, which includes the acquisition by A fibers of neurochemical features typical of C fibers, enabling these fibers to induce stimulus-evoked hypersensitivity, something only C fiber inputs normally can do.
Abstract: Inflammatory pain manifests as spontaneous pain and pain hypersensitivity. Spontaneous pain reflects direct activation of specific receptors on nociceptor terminals by inflammatory mediators. Pain hypersensitivity is the consequence of early posttranslational changes, both in the peripheral terminals of the nociceptor and in dorsal horn neurons, as well as later transcription-dependent changes in effector genes, again in primary sensory and dorsal horn neurons. This inflammatory neuroplasticity is the consequence of a combination of activity-dependent changes in the neurons and specific signal molecules initiating particular signal-transduction pathways. These pathways phosphorylate membrane proteins, changing their function, and activate transcription factors, altering gene expression. Two distinct aspects of sensory neuron function are changed as a result of these processes, basal sensitivity, or the capacity of peripheral stimuli to evoke pain, and stimulus-evoked hypersensitivity, the capacity of certain inputs to generate prolonged alterations in the sensitivity of the system. Posttranslational changes largely alter basal sensitivity. Transcriptional changes both potentiate the system and alter neuronal phenotype. Potentiation occurs as a result of the up-regulation in the dorsal root ganglion of centrally acting neuromodulators and simultaneously in the dorsal horn of their receptors. This means that the response to subsequent inputs is augmented, particularly those that induce stimulus-induced hypersensitivity. Alterations in phenotype includes the acquisition by A fibers of neurochemical features typical of C fibers, enabling these fibers to induce stimulus-evoked hypersensitivity, something only C fiber inputs normally can do. Elucidation of the molecular mechanisms responsible provides new opportunities for therapeutic approaches to managing inflammatory pain.
565 citations