The journal of pain : official journal of the American Pain Society
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Glial cell line-derived neurotrophic factor (GDNF), a survival-promoting factor for a subset of nociceptive small-diameter neurons, has been shown to exert analgesic effects on neuropathic pain. However, its detailed mechanisms of action are still unknown. In the present study, we investigated the site-specific analgesic effects of GDNF in the neuropathic pain state using lentiviral vector-mediated GDNF overexpression in mice with left fifth lumbar (L5) spinal nerve ligation (SNL) as a neuropathic pain model. A lentiviral vector expressing both GDNF and enhanced green fluorescent protein (EGFP) was constructed and injected into the left dorsal spinal cord, uninjured fourth lumbar (L4) dorsal root ganglion (DRG), injured L5 DRG, or plantar skin of mice. In SNL mice, injection of the GDNF-EGFP-expressing lentivirus into the dorsal spinal cord or uninjured L4 DRG partially but significantly reduced the mechanical allodynia in association with an increase in GDNF protein expression in each virus injection site, whereas injection into the injured L5 DRG or plantar skin had no effects. These results suggest that GDNF exerts its analgesic effects in the neuropathic pain state by acting on the central terminals of uninjured DRG neurons and/or on the spinal cells targeted by the uninjured DRG neurons. ⋯ This article shows that GDNF exerts its analgesic effects on neuropathic pain by acting on the central terminals of uninjured DRG neurons and/or on the spinal cells targeted by these neurons. Therefore, research focusing on these GDNF-dependent neurons in the uninjured DRG would provide a new strategy for treating neuropathic pain.
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The objective of this study was to assess the quality of websites presenting treatment information for postherpetic neuralgia. The term "postherpetic neuralgia treatment" was searched using the Google and Yahoo search engines. Fifty websites from each were evaluated using the Journal of the American Medical Association (JAMA) benchmarks, the Health on the Net (HON) seal, and the DISCERN instrument. The treatments suggested on each website were compared with 3 recognized first-line treatment options (antidepressants, anticonvulsants, and topical lidocaine). Less than half of the included websites fulfilled all JAMA benchmark requirements. Less than one-third of the websites displayed the HON seal. The DISCERN instrument evaluation revealed that most websites were of moderate quality. Commercial websites tended to be inferior in comparison to noncommercial websites. Most websites recommended at least 2 of the 3 recommended treatments as well as several second- and third-line treatments. One-third to one-half of websites recommended a nonbeneficial treatment. In conclusion, many different postherpetic neuralgia treatments are found on the Internet and patients may be left separating recommended treatments from nonrecommended treatments without help from their healthcare providers. ⋯ This study examined the quality of websites related to postherpetic neuralgia treatment. The results demonstrated that most websites offering advice on postherpetic neuralgia treatment are of only moderate quality and often offer treatment suggestions that are nonbeneficial. Patients and providers must use caution when taking advice from these sites.
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The observation of pain in other individuals is known to impact the cerebral activity in regions dedicated to one's nociception, as well as the behavior toward the person in pain. However, it remains unclear whether this shared representation for pain modulates somatosensory processing to nonpainful stimuli and whether this modulation is limb specific. Twenty right-handed healthy participants viewed a series of pictures depicting right hands or right feet in painful or nonpainful situations while light repetitive (25 Hz) mechanical stimuli were applied to the hand. The cortical excitability to these nonpainful stimuli was measured through the energy in the 25-Hz frequency band of electroencephalographic data. Following picture onset, a combination of nonspecific and specific modulation of cortical excitability was found. The former was widespread over the parieto-central region and likely related to factors such as attention. The latter was mostly restricted to 3 electrodes over the parietal cortex contralateral to the stimulation of the hand, and was specifically associated with the observation of others' hand in painful scenarios. This result confirms that the observation of pain can modulate somatosensory cortical excitability in an effector-specific way. The findings add to the accumulating evidence that other people's somatic pain is mapped onto the observer's sensori-motor system and offers a new paradigm to investigate potential neurophysiological changes in care providers who are often overexposed to others' pain. ⋯ This electroencephalography study demonstrates with a quick, easily implementable, and noninvasive paradigm that the change in cortical somatosensory excitability during pain observation is limb-specific, and confirms from a neuroscience perspective that being exposed to others' pain implies more than the sharing of an affective experience.
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Genetic factors play a role in the etiology of persistent pain conditions, putatively by modulating underlying processes such as nociceptive sensitivity, psychological well-being, inflammation, and autonomic response. However, to date, only a few genes have been associated with temporomandibular disorders (TMD). This study evaluated 358 genes involved in pain processes, comparing allelic frequencies between 166 cases with chronic TMD and 1,442 controls enrolled in the OPPERA (Orofacial Pain: Prospective Evaluation and Risk Assessment) study cooperative agreement. To enhance statistical power, 182 TMD cases and 170 controls from a similar study were included in the analysis. Genotyping was performed using the Pain Research Panel, an Affymetrix gene chip representing 3,295 single nucleotide polymorphisms, including ancestry-informative markers that were used to adjust for population stratification. Adjusted associations between genetic markers and TMD case status were evaluated using logistic regression. The OPPERA findings provided evidence supporting previously reported associations between TMD and 2 genes: HTR2A and COMT. Other genes were revealed as potential new genetic risk factors for TMD, including NR3C1, CAMK4, CHRM2, IFRD1, and GRK5. While these findings need to be replicated in independent cohorts, the genes potentially represent important markers of risk for TMD, and they identify potential targets for therapeutic intervention. ⋯ Genetic risk factors for TMD pain were explored in the case-control component of the OPPERA cooperative agreement, a large population-based prospective cohort study. Over 350 candidate pain genes were assessed using a candidate gene panel, with several genes displaying preliminary evidence for association with TMD status.