The journal of pain : official journal of the American Pain Society
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Administration of the neurotrophin nerve growth factor (NGF) to rats and humans has been shown to induce both thermal and mechanical hyperalgesia and is used as a model of inflammatory pain. Here we describe a mouse model of secondary hyperalgesia after NGF application. NGF was injected into the biceps femoris muscle unilaterally, and at various intervals afterwards the electromyographic (EMG) activity from the same muscle was recorded in response to mechanical von Frey hair stimulation of the plantar surface of the hind paw in isoflurane-anesthetized mice. Secondary cutaneous hyperalgesia in the hind paw reached a peak 60 minutes after injection and returned to baseline levels after an additional 60 minutes. This was followed by a second increase in EMG magnitude at 24 hours after injection that was still present after 5 days. The effects of NGF were dose-dependent, and a dose of 2 microg/g NGF had the maximal observed effect. No increase in EMG magnitude occurred on the untreated side. This study describes a quantitative mouse model of prolonged secondary cutaneous hyperalgesia after NGF-induced muscle inflammation that can be used for genetic manipulations of putative central molecular pathways that underlie secondary hyperalgesia. ⋯ This study describes the development of a novel model of NGF-induced secondary hyperalgesia. The development of this model will allow further investigations into the processes that underlie the development of secondary hyperalgesia and pain associated with the musculature.
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Injury to the nerve can produce changes in dorsal horn function and pain. This facilitated processing may be mediated in part by voltage-sensitive calcium channels. Activation of these channels increases intracellular calcium, thereby mediating transmitter release and activating cascades serving to alter membrane excitability and initiate protein transcription. Molecular techniques reveal the complexity and multiplicity of these channels. At the spinal level, blocking of several of these calcium channels, notably those of the N type, can prominently alter pain behavior. These effects are consistent with the high levels of expression on primary afferents and dorsal horn neurons of these channels. More recently, agents binding to auxiliary subunits such as the alpha2delta of these calcium channels diminish excitability of the membrane without completely blocking channel function. Drugs that bind to this site, highly expressed in the superficial dorsal horn, will diminish neuropathic pain states. Continuing developments in our understanding of these channel functions promises to advance the control of aberrant spinal functions initiated by nerve injury. ⋯ Pharmacologic studies showing the role of spinal voltage-sensitive calcium channels in neuropathic pain models provide evidence suggesting their applicability in human pain states.
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Pain draws on attentional resources, thereby disturbing the pursuit of ongoing activities. Several studies have made use of the primary task paradigm to study the disruptive function of pain on attention. In this paradigm, participants perform an attentionally demanding task, while they are occasionally distracted by mild electrical stimulation. Deterioration in task performance (in terms of speed and accuracy) is then taken as an index of attentional interference. One major finding with this paradigm was that pain catastrophizing enhances attentional interference. The current study aimed to replicate this finding and to explore the possible influence of anxiety sensitivity and injury/illness sensitivity on attentional interference. Healthy volunteers (n = 48) performed an auditory discrimination task and were thereby occasionally distracted by low electrocutaneous stimulations. The performance on the discrimination task was subsequently related to participants' scores on the Pain Catastrophizing Scale, the Anxiety Sensitivity Index, and the Injury/illness Sensitivity Index. We were unable to demonstrate an association of either injury/illness sensitivity or anxiety sensitivity with attentional interference. Results did, however, confirm the finding that pain catastrophizing enhances attentional interference. ⋯ The present study showed that pain disrupts ongoing activities. This effect is enlarged in those with high levels of pain catastrophizing and is related to the threatening nature of pain stimuli. The role of anxiety sensitivity and injury/illness sensitivity seems to differ from the role of catastrophizing and needs further research.
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The effect of pain processing on attention capacity during visual search was examined in 2 experiments. In the first experiment, we investigated whether pain draws on the same limited resources as attentional task performance. It was hypothesized that pain would negatively affect task performance under different load manipulations. Low and high load conditions of a visual search task were presented in a mixed design combined with a painfully cold or neutral cold pressor test. Performance was not affected by pain. In experiment 2, low and high load conditions were separated in different blocks to study whether pain perception was affected when task load could be anticipated. Again, pain did not significantly affect task performance. In contrast, subjective pain intensity scores were significantly lower after performing the high load compared with the low load condition. Simultaneous recordings of event-related potentials indicated an increased negativity during the pain compared with the control condition. Also, in the early (350 to 450 msec) interval of event-related potentials, an increase in negativity was found for the high load compared with the low load condition. Topographic distributions suggested that pain and task load are mediated by qualitatively different resources. ⋯ Our findings indicate that highly demanding attentional task performance and pain processing interfere as a result of difficulties in allocating attention. The clinical relevance of this finding is that performing a highly demanding task might distract attention from pain.
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Devices designed for mechanical pain threshold studies are often difficult to implement. The purpose of this study was to investigate a simple tool based on calibrated forceps to induce quantifiable mechanical stimulation in the rat on a linear scale. The most suitable protocol was tested by determining the effects of 3 repetitive measurements on both hind paws, respectively, during long-term (9 days), mid-term (1 day), and short-term (2 hours). Only threshold increase related to weight gain over long-term was observed, suggesting that moderate rat training can be used. The capacity of the device to reveal hyperalgesia was tested in a model of carrageenan-induced inflammation in the hind paw. The hyperalgesia was maximal 6 hours after carrageenan injection and progressively decreased. Similar, although more variable, responses were observed with von Frey filaments. Morphine-induced analgesia resulted in a dose-dependent increase of paw threshold. Tolerance to morphine administrated on a once daily schedule (10 mg/kg) during 5 days was revealed by a significant decrease in analgesia by day 3. Taken together, these results demonstrated accuracy of this device for easy, fast, and reproducible measure of mechanical pain threshold on rat limbs. Moreover, it allows the performance of rat testing with minimal constraint, which reduces data variability. ⋯ The calibrated forceps is an easy to use device well-suited to rapidly test mechanical pain threshold with accuracy. It is well-designed for preclinical behavioral screening of noxious or analgesic properties of molecules.