The journal of pain : official journal of the American Pain Society
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Neuropathic pain is a major clinical problem, and several animal models have been developed to investigate its mechanisms and its treatment. In this report, the role of the rostral ventromedial medulla (RVM) in the early events of the chronic constriction injury (CCI) model was investigated in behavioral and electrophysiological experiments. Placing the 4 CCI ligatures around the sciatic nerve induced large discharges and residual ongoing activity in spinal nociceptive neurons. Two weeks after CCI ligation, the rats showed behavioral hyperalgesia and allodynia as well as increased ongoing activity and responsiveness of spinal nociceptive neurons to innocuous and noxious stimuli. Blockade of excitatory synapses in the RVM by a kynurenate microinjection (2 nmol in 0.5 muL) 5 minutes before placement of the sciatic ligatures had no immediate effect on spinal neuronal activity but largely prevented the activation of spinal neurons. In kynurenate microinjected rats, behavioral hyperalgesia and allodynia developed slowly and incompletely, which corresponded with an incompletely developed hyperexcitability of spinal neurons. To the best of our knowledge, these results show for the first time that the initial response to nerve damage requires facilitation from the RVM. ⋯ The present and previous findings indicate that descending facilitation from brainstem nuclei critically contributes to the spinal hyperexcitability that underlies neuropathic pain. The present results indicate that this contribution begins at the very moment the nerve is damaged and should be prevented and treated accordingly.
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Two issues relating to prescription opioid nonmedical use that to our knowledge have not been comprehensively addressed in the peer-reviewed literature are discussed: Motives for nonmedical use and the extent of nonmedical use of prescription opioids in other countries. The United States' national annual survey on illicit drug use in the general population (National Survey on Drug Use and Health) asks respondents whether they have used prescription opioids for nonmedical purposes but does not assess motives for such use. By not assessing motives, nonmedical users who use only for pain relief and nonmedical users who have other motives for use are grouped together, but 2 recent epidemiological studies suggest that these 2 groups may differ in a propensity to have substance use-related problems. We suggest that the survey add a question that assesses motives for nonmedical use. Regarding whether countries besides the United States have problems associated with nonmedical use of prescription opioids, after searching for epidemiological surveys and other materials potentially relevant to this issue, we were unable to determine the extent of nonmedical use of prescription opioids in other countries or draw cross-national comparisons. We suggest that more countries include specific questions about nonmedical use of prescription opioids in their national epidemiological surveys. ⋯ We believe that critical information surrounding the nonmedical use of prescription opioids is not being gathered. Such information would allow for a better understanding of the problem. We invite discussion and commentaries regarding the issues we raise to more effectively address this public health issue.
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Allodynia means that innocuous tactile stimulation is felt as pain. Accordingly, cerebral activations during allodynia or touch should markedly differ. The aim of this study was to investigate whether the imagination of allodynia affects brain processing of touch in healthy subjects. Seventeen healthy subjects divided into 2 subgroups were investigated: The first group (n = 7) was familiar with allodynia, based on previous pain studies, whereas the second group (n = 10) had never knowingly experienced allodynia. Using functional magnetic resonance imaging, 2 experimental conditions were investigated. In one condition the subjects were simply touched at their left hand, whereas during the other condition they were asked to imagine pain (allodynia) during tactile stimulation of the right hand and to estimate the imagined pain on a numeric rating scale. Data processing and analysis were performed with the use of SPM5. The group analysis of all subjects revealed that tactile stimulation activated contralateral somatosensory cortices (S1 [primary] and S2 [secondary]), but the imagination of allodynia led to an additional activation of anterior cingulate cortex and bilateral activation of S2, insular cortex, and prefrontal cortices. Subgroup analysis using rating-weighted predictors revealed activation of the contralateral thalamus, anterior cingulate cortex, and amygdala and a bilateral activation of S1, S2, and insular cortex and prefrontal cortices in allodynia-experienced subjects. In contrast, allodynia-inexperienced subjects only activated contralateral S1 and bilateral S2. Just the imagination that touch is painful is able to partly activate the central pain system, but only when the subject has previous experience of this. According to our results, the medial pain system is involved in the encoding of imagined allodynia. ⋯ This article reports that pain experience is able to alter central processing of sensory stimuli. Pain knowledge appears to be able to shift "normal" tactile processing to a different quality, resulting in modified brain activity. Therefore, our study may contribute to the current understanding of human pain and will promote future research on this field.
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The nonmedical use of prescription opioids (POs), and related harmful consequences, has increased in many populations in recent years in North America. Existing survey data are typically limited to descriptive prevalence statistics, and fail to examine important determinants or circumstances (including motives) of nonmedical PO use. We advocate that such analytical queries should become integral elements in future surveys. Developing the needed survey items, however, requires conceptual thoughtfulness and rigor, especially given POs' potential for both therapeutic (eg, analgesic) effects and abuse. These considerations are concretely relevant for possible "self-medicating" nonmedical usage of POs as well as with regards to varying definitions of "pain." Furthermore, we support the harmonization of survey items on nonmedical PO use to allow for cross-national comparisons, yet also call for cross-cultural examinations into the determinants of the currently vastly discrepant medical and nonmedical PO use rates across Western countries. ⋯ We support Zacny and Lichtor's call for systematic examination of motives presented by individuals engaging in nonmedical prescription opioid use. Such motives could relate to factors instrinsic or extrinsic to the user, yet their understanding is crucial for the devising of evidence-based interventions.
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Characterization of a model of chronic orofacial hyperalgesia in the rat: contribution of NA(V) 1.8.
The purpose of this study was to develop and characterize a model of orofacial inflammatory hyperalgesia. Injection of complete Freund's adjuvant (CFA) into the upper lip/whisker pad of the rat produced significant and long-lasting thermal (> or =14 days) and mechanical (> or =28 days) hyperalgesia in the area of CFA injection. Both indomethacin and morphine, given systemically, significantly attenuated thermal hyperalgesia; the effect of morphine was shown to be opioid receptor-mediated. We also examined the contribution of the tetrodotoxin-resistant voltage-gated sodium channel Na(v)1.8 in CFA-produced orofacial mechanical hypersensitivity. Na(v)1.8 mRNA was increased > or =2.5-fold in trigeminal ganglion neurons 1 and 2 weeks after CFA treatment, and Na(v)1.8 protein was increased in the infraorbital nerve over a similar time course. The changes observed were time-dependent and had returned to baseline when examined 2 months after inflammation; there were no changes in Na(v)1.9 mRNA in trigeminal ganglion neurons after CFA treatment. In support of this, Na(v)1.8 antisense oligodeoxynucleotide treatment significantly attenuated CFA-produced mechanical hypersensitivity. These results document development of a model of inflammatory orofacial hyperalgesia, which, consistent with other reports, indicate a contribution of tetrodotoxin-resistant, voltage-gated sodium channel Na(v)1.8. ⋯ Orofacial hypersensitivity develops postoperatively as a routine course of orofacial surgery, and mechanical allodynia is characteristic of temporomandibular joint disorder. The results described in this report are novel with respect to the duration of orofacial hypersensitivity produced and suggest that pharmacological targeting of the voltage-gated sodium channel Na(v)1.8 may be useful in managing hypersensitivity.